FALL 12 News.qxd - MDS Foundation

Volume 22, Issue 2

newsletter of the myelodysplastic syndromes foundation

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MDS NEWS HIGHLIGHTS

TABLE OF CONTENTS

FROM THE GUEST EDITOR’S DESK 2

UPCOMING SYMPOSIA

ASH 2016: MDS Breakfast Symposium 9

14th International Symposium on MDS 10

RESEARCH 18

International Working Group for Prognosis in MDS

MDS/MPN International Working Group

LITERATURE HIGHLIGHTS 20

NURSING IN MDS 24

FROM THE FOUNDATION

News from Around the World 26

Testimonials 26

MDS – Just a Matter of Age? 28

PATIENTS AND CAREGIVERS LIVING WITH MDS FORUMS 30

MDS FUNDRAISING 31

AML CORNER 36

OUR CAREGIVER STORIES 42

OUR PATIENT STORIES 46

MDS CENTERS OF EXCELLENCE 56

MDSF PROFESSIONAL MEMBERS 59

CONTRIBUTIONS TO THE FOUNDATION

Gifts 61

Memorial Donations 62

Living Endowments 62

IN THIS ISSUE

FROM THE GUEST EDITOR’S DESK� The Role of Peripheral Blood FISH Cytogenetics

for the Diagnosis and Prognosis of MDSPresented by: Prof. Dr. med. Detlef Haase,Dr. med. Julie Schanz, Dr. med. Friederike Braulke,Dr. nat. techn. Christina Ganster

FALL/WINTER 2016

PRE-REGISTRATION*: http://akhcme.com/MDS*Pre-registration does not guarantee admission—please arrive early.

BIOLOGICAL ANDCLINICAL ADVANCES

IN MDS

BIOLOGICAL ANDCLINICAL ADVANCES

IN MDS

San Diego, California

DECEMBER 2, 20167:00–11:00 am

B R E A K F A S T S Y M P O S I U M

This is a Friday Satellite Symposium preceding the 58th ASH Annual Meeting.

2017

MDS 2017 will attract an international audience of researchers, clinicians,scientists and educators from around the world who deal with MDS.The MDS 2017 Symposium includes presentations delivered by renownedprofessionals on the latest developments in hematology.

www.mds2017.kenes.com

PLAN TO ATTEND OUR UPCOMING SYMPOSIAASH 2016 MDS FOUNDATIONBREAKFAST SYMPOSIUMDecember 2, 2016 • San Diego, California

14TH INTERNATIONAL SYMPOSIUM ON MYELODYSPLASTIC SYNDROMESMay 3–6, 2017 • Valencia, Spain

provide additional information in caseswith a normal karyotype, insufficientmetaphase yield or rather small cell clones.The most frequent abnormality notdetected by CBA was deletion of TET2(12%),2 followed by partial or totalmonosomy 7 (up to 9%),3,4 20q-deletion4

and 5q-deletion (in 2 to 6%),5 12p-deletion(5%)6 and loss of Y-chromosome (4%)4

(Table 1). For the proof of monosomy7/del(7q) by FISH, a negative prognosticeffect was demonstrated.3

For the TET2-deletion, it is quiteobvious that, in most cases, the deletion istoo small for detection by CBA. The sameholds true for TEL/ETV6-deletions.5 A 5q-deletion sometimes might be really krypticas observed recently in our lab (Figure 1).However, in most instances, when it ismissed by CBA this might be due toproblems to get the cell clone intoproliferation in vitro.

FISH-analysis of Peripheral Blood To our knowledge, apart from our own

studies, only two prospective trials based ona meaningful number of cases addressed thevalue of FISH from peripheral blood incomparison to bone marrow FISH-analysis.

FROM THE GUEST EDITOR’S DESK

(bm). Furthermore, certain aberrations suchas small deletions can be missed by CBA.MDS are chronic and dynamic diseaseswith a high probability of genetic evolutionover time possibly forcing the treatingphysicians to adapt their therapeuticstrategies during the course of the disease.Given the advance of effective, partiallytargeted treatments such as Lenalidomideand Dimethyl-Transferase-inhibitors (DMTI)and upcoming treatments directly targetinggenetic defects, it becomes more and moreimportant to survey abnormal clones andtheir response to therapy by frequent mon-itoring. Repeated bone marrow punctions toachieve an adequate monitoring, however,mean an unacceptable burden for most ofthe often frail MDS patients. Thusalternatives for CBA of bone marrow cellsare urgently needed. We believe that to thisrespect fluorescence in situ hybridization(FISH) -analyses of peripheral bloodrepresents an attractive option.

Additional Value of FISH in MDSwith a Normal Karyotype orInsufficient Metaphase Yield

Independent from the source of materialexamined, several groups have addressedthe question whether interphase FISH can

IntroductionChromosome banding analysis (CBA)

is still the gold standard of cytogeneticdiagnostics in MDS. The recent IPSSrevision underscored the high impact of thekaryotype to prognostication in relation toblast counts, hemoglobin value, plateletsand neutrophil counts. The higher weightwhich was assigned to cytogenetic findingsclearly improved the predictive power ofIPSS-R in comparison to the old IPSS1.However, also CBA has its limitations.These mainly reside in the need for dividingcells from bone marrow aspirate, sinceonly rarely appropriate metaphase analysiscan be successfully performed on peripheralblood. CBA also can be hampered or evenmade impossible by bone marrow fibrosiswhich can occur in a substantial subset ofpatients with MDS. The same is true forintrinsic hypoplastic MDS forms. Longlasting therapy with demethylating agentsalso may lead to hypoplastic bone marrow

Guest Editorial: The Role of Peripheral Blood FISH Cytogenetics for theDiagnosis and Prognosis of MDS

Prof. Dr. med. Detlef HaaseDr. med. Julie SchanzDr. med. Friederike BraulkeDr. nat. techn. Christina GansterDepartment of Hematology and OncologyUniversity of GöttingenGöttingen, Germany

2

GUEST EDITORIAL

NAbnormality % Localization (pts. examined) Author

TET2-Deletion 11.5 4q24 44 De Olivera (2013), Med. Oncol2

EGR1-Deletion 5.6 5q31 1473 Lai Y-Y (2015), Leuk Res4

2.7* Mallo (2008), haematologica5

1.9#4.6+

-7/7q- 3.9 7cen->7q34 433 Adema (2013), Leuk Res3

8.7 “ 1473 Lai Y-Y (2015), Leuk Res4

+8 6.3 8pter ->8qter 1473 Lai Y-Y (2015), Leuk Res4

TEL/ETV6- 4.6 12p13 367 Braulke (2015),Deletion Genes Chromos. Cancer6

20q-Deletion 5.8 20q11->20q13 1473 Lai Y-Y (2015), Leuk Res4

Y-loss 4.1 Yq11->Yqter 1473 Lai Y-Y (2015, Leuk Res4

*At least 20 metaphases analyzed; #10-19 metaphases; +1 –9 metaphases

Table 1. FISH-abnormalities in MDS with normal karyotype by CBA, published data

3

In 2009 with support by the MDSFoundation, an international multicentricdiagnostic study with participation of 15centers from 8 countries was launchedaiming to answer the question whether “aperipheral blood (pb) sample will yield thesame diagnostic and prognosticcytogenetic data as the concomitant bonemarrow (bm) in myelodysplasia”. In a pilotphase, the concordance among sites provedto be excellent. In the second phase of thestudy, a total of 100 MDS patients wereprospectively accrued to the study. A FISHpanel consisting of eight probe sets,designed to detect the most frequentchromosome abnormalities in MDS [-5/5q,-7/7q-/der(1;7), +8/8q-, -11/+11/11q-/add(11q), 12p-/+21/t(12;21), -13/13q-, 17p-and 20q-/i(20q)/i(20p)], was performed onboth specimen types, pb and bm. CBA ofpb was unsuccessful in 51% of casesexamined. FISH was informative(concordant with bm/pb CBA) in 95% ofcases, with 51% of pb FISH demonstratingan abnormal clone. FISH was discordant in5% of bm and pb samples, while CBA andFISH of bm and pb were discordant in 12%and 9% of samples, respectively.

In 12 cases, abnormal CBA findingswith normal FISH findings were explainedby the failure of the FISH panel to trace thedescribed clonal chromosomal abnormalities (e.g. t(8;10), trisomy 19, -Y). Whenbm and pb FISH indicated an anomaly,typically the percentage of positive cells

was lower in the pb than that observed inthe bm, as can be expected. It wasconcluded that while CBA of bm remainsthe “gold standard” at diagnosis of MDS,evaluation of interphase nuclei by FISHfrom pb could be used for follow-up (non-diagnostic) on MDS patients. It may beequally informative, as well as less costlyand stressful, than a bm sample.Combination of both techniques canincrease sensitivity and number ofinformative cases.7

In a prospective study, Coleman andcolleagues compared FISH results frombone marrow with peripheral blood in 48cases with suspected MDS or AML. AFISH panel of four probes detecting -5/5q,-7/7q-, +8 and 20q- was applied. Theyfound abnormal pb FISH results in 69% of26 cases with abnormal bm FISH. On theother hand pb FISH was abnormal in 23%of 22 patients with normal bm FISH. In theentire cohort of 433 patients FISH ingeneral was abnormal in 14% of cases with<20 normal metaphases and in 19% ofcases with no metaphase yield. By CBAalone 26.3% had an abnormal karyotype.By combination with FISH karyotypicabnormalities were found in 31.4% ofpatients. 136 pts. had any cytogeneticchange of which 16.2% were identifiedonly by FISH.8

CD34+ FISH of Peripheral BloodBackground

In patients with MyelodysplasticSyndrome (MDS) chromosomal aberrationsrepresent an important component inpathogenesis, diagnosis, prognosis andtherapeutic decision making. The goldstandard method for cytogenetic diagnosticsin MDS is still the conventionalchromosome banding analysis of bonemarrow metaphases, providing an overviewof the whole chromosome complement andthe assessment of the karyotype accordingto the International System of HumanCytogenetic Nomenclature (ISCN).9 Formany chromosomal anomalies typical forMDS, corresponding probes are available forFluorescence-in-Situ-Hybridization (FISH)analyses. Several studies have focused onthe possible benefit of additional FISH-testing of bone marrow blood cells inMDS.2-8,10-14 In 2001, Vehmeyer et al.described an increased number of myeloidCD34+ progenitor cells circulating in theperipheral blood of MDS patients.15 Theyfound a positive correlation between theamount of CD34+ circulating cells in pband advanced MDS stages. Later, Haase etal. could show that in MDS and acutemyeloid leukemia (AML) CD34+/CD38-bone marrow cells show the same clonalchromosomal aberrations as observed inroutine metaphase analysis.16,17 Based onthese data, we chose CD34+ myeloidprogenitor cells circulating in peripheralblood for further analyses.

MethodFirst, we tested a FISH-probe panel on

unselected and enriched CD34+ bonemorrow blood cells in addition to sufficientkaryotyping on bm metaphases. CD34+myeloid progenitor cells circulating in theperipheral blood were enriched usingimmunomagnetic activated cell separation(MACS®, Miltenyi Biotec GmbH,Bergisch Gladbach, Germany). Out of20ml of pb, a number of 80 000 to 400 000CD34+ cells could be enriched (0.2-1.5%of all peripheral nucleated cells).18 Afterimmunomagnetic cell sorting, CD34+ cellswere analyzed by FISH techniques usingcomprehensive FISH-probes, detecting

Figure 1. Proof of a kryptic EGR1-/5q-deletion by relocalization of the banded metaphase and FISH-analysis with the informative EGR1-FISH-probe at the identical metaphase (Haase, unpublished)

4

most of the aberrations typical for MDS:LSI 1p36SO/1q25SG™, LSI EGR1(5q31)/D5S23,D5S721(5p15.2)™, LSI CSF1R(5q33-q34)/D5S23,D5S721 (5p15.2)™,LSI D7S522(7q31)/CEP7™, LSI CEP8Spectrum Orange™, LSI MLL DualColor™,LSI TEL/AML1 ES™, LSI 13(RB1)13q14™, LSI IGH/BCL2™, LSI TP53(17p13.1)™, LSI D20S108(20q12)™, CEPX SpectrumOrange™/Y SpectrumGreen™(Abbott GmbH & Company, KG, Wiesbaden,Germany) and XL TET2TM (MetaSystemsGmbH, Altussheim, Germany).CD34+FISH-trial

In a small pilot study, we performed theproof of principle of a new method tomonitor MDS patients from peripheralblood.18 We could show that analysingCD34+PB cells by FISH usingcomprehensive probe panels is feasible inlow-risk as well as in high risk MDSpatients. Furthermore, the results fromperipheral blood correlated well with theresults of conventional banding analyses asthe gold standard method. In a second stepwe started a prospective Germandiagnostic study (CD34+FISH-Study,ClinicalTrials.gov: NCT01355913) tofollow MDS patients by sequential FISHanalyses from pb in a sense of a molecular-cytogenetic monitoring. In total, 360 MDSpatients were monitored up to 3 years bysequential FISH analyses of immuno-magnetically enriched CD34+ peripheralblood cells using comprehensive FISHprobe panels every 2–3 months with a totalnumber of 19,516 FISH analyses.19 Inevery case of bone marrow aspiratesavailable, comparative additional FISHanalyses of unselected and selected CD34+bm were performed in parallel toconventional banding analyses. We couldshow that CD34+pb-FISH results correlatesignificantly with bm-banding analysis.Furthermore, we demonstrated that theenrichment step is necessary using pbbecause otherwise the clone sizes detectedby FISH are too small and too close to theprobes cut-off value for valid cytogeneticinformation during follow-up. Our datashow that the enrichment step was notrequired in case of FISH analyses on bm

cells, the clone sizes differed not signif-icantly between enriched and unselectedbm FISH analyses.19

This method was chosen for cytogeneticmonitoring in a prospective Germanphase-I clinical trial for heavily pretreatedhigh-risk MDS patients who received acombination therapy of Azacitidine andLenalidomide (AZALE, University ofDresden, Germany, ClinicalTrials.gov:NCT00923234).20 We could show thatCD34+pb-FISH was able to serve as acytogenetic monitoring to detect responseto therapy as well as treatment failure.

The method was also applied in anotherprospective German phase-II-clinical trialfor low-risk MDS patients with isolated5q-deletion to be treated with lenalidomide(LE-MON-5, University of Düsseldorf,Germany, EudraCT:2008-001866-10) andcould prove its feasibility as a reliable non-invasive cytogenetic monitoring from pb.21

Evaluation of the PrognosticImpact of CD34+pb FISH

Since FISH analyses of CD34+ cellsfrom the peripheral blood were establishedas a reliable method to perform cytogeneticanalyses in MDS, there was some interestwhether the results of this method can beused to evaluate the prognosis in MDS asvalid as by chromosome banding analysis.So far, the evaluation of prognostic systemsin MDS, most actually the IPSS-R,1 wasbased on chromosome banding analyses(CBA) without considering results fromFISH. However, in the daily clinicalpractice, a method to evaluate prognosisfrom a peripheral blood sample without theneed to perform a bone marrow biopsy,would be of great value, especially inpatients that are not eligible for or notwilling to accept a BM biopsy. Thus, aretrospective analysis including a totalnumber of 3,230 patients with MDS wasconducted in order to investigate thecomparability of the prognostic predictivepower in CBA versus CD34 pB FISH.22

Based on our results that analyzingcirculating CD34+ cells by FISH is areliable method to survey an aberrant clonein peripheral blood, that it is feasible inhigh-risk as well as in low-risk MDS and isrepresentative for the clonal situation in thebone marrow,18,19 it was of special interestwhether: a) prognostic classification byIPSS and IPSS-R based on CD34+ pBFISH is reliable, b) severe limitations are

Figure 2. Cytogenetic prognostic classification as defined by IPSS/-R by using CD34+pb- FISH22

The results from

peripheral blood

correlated well with the

results of conventional

banding analyses as the

gold standard method.

5

observable and c) the method is able toreplace the gold standard of cytogeneticprognostic classification, the CBA.

The study demonstrated that the cyto-genetic classification as defined by IPSS(Figure 2) and IPSS-R is feasible andreliable.

In a second step, it was proven by amultivariate analyses adding a controlgroup of 2,902 patients analyzed by CBApublished before,23 that the results fromCD34+ FISH are not significantly differentregarding their predictive power (Figure3). However, the study also showed thatthere are some limitations that lead to theconclusion that CD34+pb-FISH is amethod able to amend, but not to replaceCBA. The main points are:a) Abnormalities not detectable by the

probe panel used in CD34+ pB FISHare overlooked

b) Different clones, possibly evolved froman evolutional process, cannot beseparated by FISH. Unrelated clones areundetectable by this method.

c) The complexity of the clone and thenumber of abnormalities, which is ofgreat prognostic importance, is sometimesunderestimated by CD34+pb-FISH.Thus, taken these results together, CBA

remains the gold standard of prognosticclassification of MDS. However, CD34+pb-FISH can be of great value as analternative method if CBA is not feasible.

Clonal EvolutionIt is well known that clonal evolution is

associated with an adverse prognosis inMDS patients.24,25 Principally, evolution ofthe clone towards complex or morecomplex changes can occur via differentpathways: a) a stepwise accumulation ofkaryotype abnormalities over the time ofthe disease and b) a catastrophic singleevent that results in a substantialchromosomal instability, finally resulting ina multitude of chromosomal abnormalitiesand rearrangements and cell to cellvariations. In MDS, a clonal evolution thattook place in the past can be oftenobserved at the time of the first diagnosiswhen several different clones evolvingfrom each other are seen in the firstcytogenetic examination. When evolutionoccurs as a stepwise process or later in thedisease its detection can be difficultbecause this is only possible by performingfrequent sequential cytogenetic analysesduring the course of the disease. However,the observation of the clone in vivo over along time period is scientifically desirable,but ethically problematic because it isunacceptable for the patient to performbone marrow punctations in short timeintervals. Beyond its prognostic meaning,a “clonal surveillance” would be of greatinterest to understand the mechanisms ofclonal evolution and their patterns in MDSand their link to the course of the disease.Performing CD34+ FISH on peripheralblood has the potential to overcome theproblem of sequential cytogenetic analyses

by offering a method that is indolent forthe patient, valid and reliable. Thus, themethod will be of great value to understandclonal evolution in MDS in the future. TheGerman LeMon5 trial was a first step inthat direction. In this study, a largenumber of patients with del(5q) MDS weretreated with lenalidomide and thecytogenetic course of these patients wasobserved using the CD34+ pb-FISHmethod in a frequently repeated design.First results from this study and the clonalcourse of these patients will be publishedin the near future.

DiscussionThere is an increasing body of evidence

provided by several independent groupsand international collaborations that FISHanalyses of peripheral blood in MDS addssignificantly to an improvement of clinicalmanagement. FISH analyses of pb samplesare feasible, reliable and can cover mostrelevant cytogenetic changes if an adequatecomprehensive probe panel is used.7,18,19

Pb FISH is a good alternative ifchromosome banding analysis of bmspecimens is not possible. A furtherattractive option is to use pb FISH tofrequently monitor the karyotype duringthe course of the disease and to followabnormal clones and/or timely detectclonal evolution. It is also a good device toobjectivate therapy response without theneed for repeated bone marrowpunctations. The use of nonenriched pbcells for FISH however, bears the risk to

Figure 3. Cytogenetic prognostic classification comparing CD34+ pB FISH and CBA (Braulke at al. 2015)

Results from multivariate analyses: IPSS- and IPSS-R cytogenetic subgroups and IPSS prognosticsubgroups in CD34+ pB FISH vs. CBA

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miss a substantial portion of smallerclones. Also, the follow-up of unenrichedpb might be problematic since the portionof cells not belonging to the MDS clonecan fluctuate over time interfering with areliable longitudinal survey of clones. Tothis respect pb FISH can be optimized bythe use of immunomagnetically enrichedCD34+ blood cells. This technique canovercome the above mentioned flaws withquite low additional expenditure andacceptable costs. Even a prognosticationadapted to the IPSS/IPSS-R is possible.The individual course from our lab shownin Figure 4 exemplifies the value andpotential of the CD34-FISH-technique(unpublished data).

In this borderline case between RA andRAEB-1, we always had to struggle withlow metaphase yield making cytogeneticsunreliable. However, by applying CD34pb-FISH we were able to establish a reliableand informative cytogenetic monitoringnevertheless. We even could detectabnormalities not found in the metaphasefraction. It allowed us to detect clonalevolution and leukemic transformationvery early before clinical deterioration andto react on this by rapid start of therapyescalation ending up in successfulallogeneic stem cell transplantation andenduring complete remission.

Comment on Guest Editorial inMDS News, Vol. 22, Issue 1

We were asked to comment on theGuest Editorial in the spring/summernewsletter of the MyelodysplasticSyndromes Foundation. Here, Tucker andKarsan discussed the superiority of DNAmicroarray analysis (DMA) over conven-tional cytogenetics and that a combinationof DMAs and next generation panelsequencing (NGS) might make karyotypeanalysis redundant in the future.

Micorarrays can be performed on bonemarrow as well as on peripheral blood27,28

and could therefore, just as FISH,overcome the need for bone marrow andfor metaphases. Unlike FISH, microarrayswould detect aberrations genome-wide andwere therefore thought to increase thenumber of informative cases.

However, both methods, DMAs andNGS, at least at the actual state, have theirown specific limitations, especiallyconcerning sensitivity, uncovering ofclonal architecture and the uncertainty ofprognostic relevance tested in a largepatient cohorts not treated with diseasemodifying therapies. The authors arguethat there are fewer abnormalities in thecytogenetic risk categories compared to themultitude of those observed. From a certainpoint of view, this is correct. However, therarity of these changes by itself implies thatonly a small subgroup of patients (8.9%)26

is affected by them, thus making thisproblem much smaller as claimed byTucker and Karsan. At the moment, aninternational activity of the IWG-PM isunder way collecting prognostic data ofvery rare isolated cytogenetic abnormalities

Figure 4. Course of FISH results in a patient with RAEB-1 and initially isolated del(5q). The columns show the proportion of cells affected by cytogenetic aberrations (clone size) in CD34+peripheral blood cells (PBC) the numbers above each show the percentage of the resp. abnormality. Inaddition to 5q-, the patient gained as a further subclonal aberration a loss of one AML1-signal 12months after start of monitoring of CD34+ PBC without significant clinical signs of progression.Nevertheless 5-Aza was started. Before, bm examinations at months 0 and 6 had revealed a borderlinemorphology between RA and RAEB-1 and confirmed FISH results by metaphase analysis althoughshowing a low metaphase yield. At month 15 further cytogenetic progression was observed (only byCD34+pb FISH) with an increase of cells with loss of one AML1-signal and the emergence of two newadditional (subclonal) changes (cells with loss of the second AML1-signal and monosomy 7). Again nosigns of clinical deterioration were evident. Worried about that, we performed a bone marrowexamination showing the transformation into a hypoplastic AML. Therapeutic strategy was modifiedand an allogeneic stem cell transplantation was performed at month 18 with the patient now incontinuous complete remission since over three years.

There is an increasing

body of evidence provided

by several independent

groups and international

collaborations that FISH

analyses of peripheral

blood in MDS adds

significantly to an

improvement of clinical

management.

7

in MDS, and data will be published soon.We agree with the statement that DAM isvery suitable to detect kryptic CNAs undcopy number neutral LOH (CN-LOH) andthus can add important geneticinformation. However, this is a quite rarephenomenon in MDS too.

In our lab conventional cytogenetics,FISH-analysis, DMA as well as NGS arewell-established and used for researchpurposes as well as in routine analyses,which allows us to judge about the pros andcons of each method in direct comparison.We evaluated 146 MDS/sAML cases withconventional karyotyping, FISH (56% ofcases on circulating CD34+ cells) andDMA (40% of cases on circulating CD34+cells). By conventional karyotyping, thefrequency of informative abnormal caseswas 60%, by FISH it was 58%. Thefrequency of informative cases increased to71% if FISH and DMA were considered. In11/146 (8%) cases DMA identified anabnormality when conventional karyotypingand FISH did not (6x due to CN-LOH, 5Xdue to rare abnormalities below the ~10 Mbresolution of standard karyotyping).Aberrations, only detected by DMA andnot by FISH, were CN-LOHs in regionscommonly affected in MDS with knownprognostic significance; but also rareaberrations with unknown prognosticsignificance. In cases with normalconventional karyotyping and normalFISH, DMAs could probably addcytogenetic information. Microarray wouldbe useful to prove clonality, but so far,cryptic aberrations are often of unknownprognostic significance and the effect ofthe amount of genetic material abnormalby DMA on prognosis is unclear. To thisrespect we have to keep in mind that thedata set used for the establishment of theIPSS-R is unique, due to its size (7012fully characterized pts.) and due to the factthat pts. were not treated with diseasemodifying therapies, thus more or lessrepresenting natural course of the disease.To be able to define prognosis of rareDMA-abnormalities would long for a dataset of comparable size and features, whichis very unlikely to be achievable ever

again. Another problem is the lowsensitivity of DMA which ranges between20 and 30% clone size, while sensitivity ofCBA is in the range of 10% and ofinterphase FISH around 5%. Anotherimportant point is that, at the moment, noother method than CBA can decipher agiven clonal architecture directly. Thatmeans that without CBA you can do somestatistical calculations but you rarely canbe sure that the abnormalities you detectbelong to one single clone, reside incompletely independent clones or aredistributed over several differentsubclones. While the prognostic relevanceof different combinations of cytogeneticchanges was clarified26 this has not beencomprehensively achieved for NGS, orcombined results of DMAs and NGS.

We think that, at the moment, none ofthe discussed technologies can substituteanother one. However, the combined use ofthem can be beneficial for individualpatient´s management increasing theamount of genetic information substantially.

References1. Peter L. Greenberg, Heinz Tuechler, Julie

Schanz, Guillermo Sanz, Guillermo Garcia-Manero, Francesc Solé, John M. Bennett,David Bowen, Pierre Fenaux, FrancoisDreyfus, Hagop Kantarjian, Andrea Kuendgen,Alessandro Levis, Luca Malcovati, MarioCazzola, Jaroslav Cermak, Christa Fonatsch,Michelle M. Le Beau, Marilyn L. Slovak, OttoKrieger, Michael Luebbert, JaroslawMaciejewski, Silvia Magalhaes YasushiMiyazaki, Michael Pfeilstoecker, MikkaelSekeres, Wolfgang R. Sperr, Reinhard Stauder,Sudhir Tauro, Peter Valent, Teresa Vallespi,Arjan van de Loosdrecht, Ulrich Germing, andDetlef Haase. Revised International PrognosticScoring System (IPSS-R) for MyelodysplasticSyndromes. Blood. 2012 Sep 20;120(12):2454–65. Epub 2012 Jun 27

2. de Oliveira FM, Miguel CE, Lucena-AraujoAR, de Lima AS, Falcão RP, Rego EM. FISHanalysis for TET2 deletion in a cohort of 362Brazilian myeloid malignancies: correlationwith karyotype abnormalities. Med Oncol.2013 Mar;30(1):483. doi: 10.1007/s12032-013-0483-1. Epub 2013 Feb 7.

3. Ademà V, Hernández JM, Abáigar M, LumbrerasE, Such E, Calull A, Dominguez E, Arenillas L,Mallo M, Cervera J, Marugán I, Tormo M,García F, González T, Luño E, Sanzo C, MartínML, Fernández M, Costa D, Blázquez B,Barreña B, Marco F, Batlle A, Buño I, Martínez-Laperche C, Noriega V, Collado R, Ivars D,

Carbonell F, Vallcorba I, Melero J, Delgado E,Vargas MT, Grau J, Salido M, Espinet B, MeleroC, Florensa L, Pedro C, Solé F. Application ofFISH 7q in MDS patients without monosomy 7or 7q deletion by conventional G-banding cyto-genetics: does -7/7q- detection by FISH haveprognostic value? Leuk Res. 2013 Apr;37(4):416-21. doi: 10.1016/j.leukres.2012. 12.010.Epub 2013 Jan 18.

4. Lai YY, Huang XJ, Li J, Zou P, Xu ZF, Sun H,Shao ZH, Zhou DB, Chen FP, Liu ZG, Zhu HL,Wu DP, Wang C, Zhang Y, Li Y, Hou M, Du X,Wang X, Li W, Lai YR, Zhou J, Zhou YH,Fang MY, Qiu L, Wang XM, Zhang GS, JiangM, Liang YM, Zhang LS, Chen XQ, Bai H, LinJY. Standardized fluorescence in situhybridization testing based on an appropriatepanel of probes more effectively identifiescommon cytogenetic abnormalities in myelo-dysplastic syndromes than conventionalcytogenetic analysis: a multicenter prospectivestudy of 2302 patients in China. Leuk Res.2015 May;39(5):530-5. doi:10.1016/j.leukres.2015.02.005. Epub 2015 Feb 18.

5. Mallo M1, Arenillas L, Espinet B, Salido M,Hernández JM, Lumbreras E, del Rey M,Arranz E, Ramiro S, Font P, González O,Renedo M, Cervera J, Such E, Sanz GF, LuñoE, Sanzo C, González M, Calasanz MJ,Mayans J, García-Ballesteros C, Amigo V,Collado R, Oliver I, Carbonell F, Bureo E,Insunza A, Yañez L, Muruzabal MJ, Gómez-Beltrán E, Andreu R, León P, Gómez V, SanzA, Casasola N, Moreno E, Alegre A, MartínML, Pedro C, Serrano S, Florensa L, Solé F.Fluorescence in situ hybridization improvesthe detection of 5q31 deletion in myelo-dysplastic syndromes without cytogeneticevidence of 5q-. Haematologica. 2008 Jul;93(7):1001-8. doi: 10.3324/haematol.13012.

6. Braulke F, Müller-Thomas C, Götze K,Platzbecker U, Germing U, Hofmann WK,Giagounidis AA, Lübbert M, Greenberg PL,Bennett JM, Solé F, Slovak ML, Ohyashiki K,Le Beau MM, Tüchler H, Pfeilstöcker M,Hildebrandt B, Aul C, Stauder R, Valent P,Fonatsch C, Bacher U, Trümper L, Haase D,Schanz J. Frequency of del(12p) is commonlyunderestimated in myelodysplastic syndromes:Results from a German diagnostic study incomparison with an international controlgroup. Genes Chromosomes Cancer. 2015Dec;54(12):809-17. doi: 10.1002/gcc.22292.Epub 2015 Sep 10.

7. Athena M. Cherry, Marilyn L. Slovak, Lynda J.Campbell, Kathy Chun, Virginie Eclache,Detlef Haase, Claudia Haferlach, BarbaraHildebrandt, Anwar M. Iqbal, Suresh C.Jhanwar, Kazuma Ohyashiki, Francesc Sole,Peter Vandenberghe, Daniel L. VanDyke,Yanming Zhang, and Gordon W. Dewald(2012) Will a Peripheral Blood (PB) SampleYield the Same Diagnostic and PrognosticCytogenetic Data as the Concomitant BoneMarrow (BM) in Myelodysplasia? Leuk Res.Jul;36(7):832-40. Epub 2012 Apr 25.

8

8. Coleman JF1, Theil KS, Tubbs RR, Cook JR.Diagnostic yield of bone marrow andperipheral blood FISH panel testing inclinically suspected myelodysplastic syndromesand/or acute myeloid leukemia: a prospectiveanalysis of 433 cases. Am J Clin Pathol.2011 Jun;135(6):915-20. doi: 10.1309/AJCPW10YBRMWSWYE.

9. ISCN: an international system for humancytogenetic nomenclature (2016)/editors, JeanMcGowan-Jordan, Annet Simons, MichaelSchmid. Basel; New York: Karger [2016]

10. Costa D, Valera S, Carrió A, Arias A, Muñoz C,Rozman M, et al. Do we need to dofluorescence in situ hybridization analysis inmyelodysplastic syndromes as often as we do?Leuk Res. 2010;34:1437-41.

11. Jiang H, Xue Y, Wand Q, Pan J, Wu Y, ZhangJ, et al. The utility of fluorescence in situhybridization analysis in diagnosing myelo-dysplastic syndromes is limited to cases withkaryotype failure. Leuk Res. 2012;36:448-52.

12. Pitchford CW, Hettinga AC, Reichard KK.Fluorescence In Situ Hybridization testing for -5/5q-, -7/7q-, +8, and del(20q) in PrimaryMyelodysplastic Syndrome Correlates WithConventional Cytogenetics in the Setting of anAdequate Study. Am J Clin Pathol. 2010;133:260-64.

13. Kwon WK, Lee JY, Mun YC, Seong CM,Chung WS, Huh J. Clinical utility of FISHanalysis in adition to G-banded karyotype inhematologic malignancies and proposal ofpractical research. Korean J Hematol. 2010;45:171-76.

14. Pinheiro RF and Chauffaille MLLF.Comparison of I-FISH and G-banding for thedetection of chromosomal abnormalitiesduring the evolution of myelodysplasticsyndrome. Braz J Med Biol Res. 2009;42:1110-1112.

15. Vehmeyer K, Haase D, Alves F. Increasedperipheral stem cell pool in MDS: an indicationof disease progression? Leuk Res. 2001;25:955-59.

16. Haase D, Feuring-Buske M, Könemann S,Fonatsch C, Troff C, Verbeek W, Pekrun A,Hiddemann W, Wörmann B. Evidence formalignant transformation in acute myeloidleukemia at the level of early hematopoieticstem cells by cytogenetic analysis of CD34+subpopulations. Blood. 1995;86(8):2906-2912.

17. Haase D, Feuring-Buske M, Schäfer C, SchochC, Troff C, Gahn B, Hiddemann W, WörmannB. Cytogenetic analysis of CD34+subpopulations in AML and MDS character-ized by the expression of CD38 and CD117.Leukemia. 1997;11(5):674-679.

18. Braulke F, Schanz J, Jung K, Shirneshan K,Schulte K, Schuetze C, et al. FISH Analysis ofCirculating CD34+ Cells as a New Tool forGenetic Monitoring in MDS: Verification ofthe Method and Application to 27 MDSPatients. Leuk Res. 2010;34:1296-1301.

19. Braulke F, Jung K, Schanz J, Goetze K, Muller-Thomas C, Platzbecker U, et al. Molecularcytogenetic monitoring from CD34+peripheral blood cells in myelodysplasticsyndromes: first results from a prospectivemulticenter German diagnostic study. LeukRes. 2013;37:900-906.

20. Platzbecker U, Braulke F, Kündgen A, GötzeK, Bug G, Schönefeldt C, Shirneshan K, RölligC, Bornhäuser M, Naumann R, Neesen J,Giagounidis A, Hofmann WK, Ehninger G,Germing U, Haase D, Wermke M.: Sequentialcombination of azacitidine and lenalidomide indel(5q) higher-risk myelodysplastic syndromesor acute myeloid leukemia: a phase I study.Leukemia. 2013 Jun;27(6):1403-7.

21. Schuler E, Giagounidis A, Haase D,Shirneshan K, Büsche G, Platzbecker U, et al.Results of a multicenter prospective phase IItrial investigating the safety and efficacy oflenalidomide in patients with myelodysplasticsyndromes with isolated del(5q) (LE-MON 5).Leukemia. 2015;30(7):1580-1582.

22. Braulke F, Platzbecker U, Müller-Thomas C,Götze K, Germing U, Brümmendorf TH,Nolte F, Hofmann WK, Giagounidis AA,Lübbert M, Greenberg PL, Bennett JM, SoléF, Mallo M, Slovak ML, Ohyashiki K, LeBeau MM, Tüchler H, Pfeilstöcker M,Nösslinger T, Hildebrandt B, Shirneshan K,Aul C, Stauder R, Sperr WR, Valent P,Fonatsch C, Trümper L, Haase D, Schanz J.Validation of cytogenetic risk groups accordingto International Prognostic Scoring Systems byperipheral blood CD34+FISH: results from aGerman diagnostic study in comparison withan international control group. Haematologica.2015 Feb;100(2):205-13. doi: 10.3324/haematol.2014.110452. Epub 2014 Oct 24.

23. J. Schanz, H. Tüchler, F. Solé, M. Mallo, E.Luño, J. Cervera, I. Granada, B. Hildebrandt,M.L. Slovak, K. Ohyashiki, C. Steidl1, C.Fonatsch, M. Pfeilstöcker, T. Nösslinger, P.Valent, A. Giagounidis, C. Aul, M. Lübbert, R.Stauder, O. Krieger, Guillermo Garcia-Manero,Stefan Faderl, Sherry Pierce, M.M. Le Beau,J.M. Bennett, P. Greenberg, U. Germing and D.Haase. A new, comprehensive cytogeneticscoring system for primary myelodysplasticsyndromes and oligoblastic AML following

MDS derived from an international databasemerge. J Clin Oncol. 2012 Mar 10;30(8):820-9. doi: 10.1200/JCO.2011.35.6394. Epub 2012Feb 13

24. Bernasconi P, Klersy C, Boni M, CaviglianoPM, Giardini I, Rocca B, Zappatore R,Dambruoso I, Calvello C, Caresana M,Lazzarino M. Does cytogenetic evolution haveany prognostic relevance in myelodysplasticsyndromes? A study on 153 patients from asingle institution. Ann Hematol. 2010 Jun;89(6):545-51. doi: 10.1007/s00277-010-0927-z. Epub 2010 Mar 9.

25. Claudia Haferlach, Melanie Zenger, TamaraAlpermann, Susanne Schnittger, WolfgangKern, Torsten Haferlach. Cytogenetic ClonalEvolution in MDS Is Associated with Shiftstowards Unfavorable Karyotypes According toIPSS and Shorter Overall Survival: A Study on988 MDS Patients Studied Sequentially byChromosome Banding Analysis. Blood. 2011118:968, abstract

26. J. Schanz, H. Tüchler, F. Solé, M. Mallo, E.Luño, J. Cervera, I. Granada, B. Hildebrandt,M.L. Slovak, K. Ohyashiki, C. Steidl1, C.Fonatsch, M. Pfeilstöcker, T. Nösslinger, P.Valent, A. Giagounidis, C. Aul, M. Lübbert, R.Stauder, O. Krieger, Guillermo Garcia-Manero,Stefan Faderl, Sherry Pierce, M.M. Le Beau,J.M. Bennett, P. Greenberg, U. Germing and D.Haase. A new, comprehensive cytogeneticscoring system for primary myelodysplasticsyndromes and oligoblastic AML followingMDS derived from an international databasemerge. J Clin Oncol. 2012 Mar 10;30(8):820-9. doi: 10.1200/JCO.2011.35.6394. Epub 2012Feb 13

27. Mohamedali AM, Gaken J, Ahmed M, Malik F,Smith AE, Best S, et al. High concordance ofgenomic and cytogenetic aberrations betweenperipheral blood and bone marrow inmyelodysplastic syndrome (MDS). Leukemia.2015 Sep; 29(9): 1928-1938.

28. Ganster C, Shirneshan K, Salinas-Riester G,Braulke F, Schanz J, Götze KS, et al. AComprehensive Genetic Analysis of MDSPatients From Peripheral Blood CombiningFISH- and SNP-Array-Analysis. ASH AnnualMeeting Abstracts 2012 November 16, 2012;120(21):4926.

Take a look at the resourcesavailable for you on our website: http://www.mds-foundation.org/

clinical-toolbox

HAVE YOU ACCESSED THECOMPLETE SET OF TOOLS IN

THE MDS ACADEMYCLINICAL TOOLBOX?

DECEMBER 2, 20167:00 – 11:00 amSan Diego Convention Center, San Diego, CaliforniaWest Building, Room 6ABreakfast will be served from 7:00 to 7:30 am.

JOIN US FOR A BREAKFAST SYMPOSIUM

BIOLOGICAL AND CLINICAL ADVANCES IN MDS

9

THE AMERICAN SOCIETY OF HEMATOLOGY 58TH ANNUAL MEETING & EXPOSITION • DECEMBER 2016

UPCOMING MEETINGS

PROGRAM OVERV IEWNew clinical classification of MDS, as well as the evaluation ofthe implications of molecular mutations, have generated valuableadvances for aiding management of patients with this disease.These recent findings will be discussed during this program. Theunique nature of treatment-related MDS as a specific subset ofMDS will also be reviewed. Given the understanding ofimmunologic abnormalities in MDS, therapeutic interventionsusing immune checkpoint inhibitors and T-cell based therapieswill add to this discussion, as will a number of the noveltreatments using biologic targeted approaches for anemias andhigher risk patients.

ACCRED I TAT IONCME/CE provided by AKH Inc., Advancing Knowledge in Healthcare.Physicians: This activity has been planned and implemented inaccordance with the accreditation requirements and policies of theAccreditation Council for Continuing Medical Education (ACCME)through the joint providership of AKH Inc., Advancing Knowledge inHealthcare, and The Myelodysplastic Syndromes (MDS) Foundation.AKH Inc., Advancing Knowledge in Healthcare, is accredited by theACCME to provide continuing medical education for physicians. AKH Inc., Advancing Knowledge in Healthcare, designates this liveactivity for a maximum of 3.5 AMA PRA Category 1 Credit(s)™.Physicians should claim only credit commensurate with the extent oftheir participation in the activity.Physician Assistants: NCCPA accepts AMA PRA Category 1Credit™ from organizations accredited by ACCME. Pharmacists: AKH, Inc., Advancing Knowledge in Healthcare isaccredited by the Accreditation Council for Pharmacy Education asa provider of continuing pharmacy education. AKH, Inc., AdvancingKnowledge in Healthcare approves this knowledge-based activityfor 3.5 contact hour(s) (0.35 CEUs). UAN 0077-9999-16-072-L04-P.Nursing: AKH, Inc., Advancing Knowledge in Healthcare isaccredited as a provider of continuing nursing education by theAmerican Nurses Credentialing Center’s Commission onAccreditation. This activity is awarded 3.5 Contact Hours.

TARGET AUD IENCEThis activity is intended for physicians, oncology nurses, nursepractitioners, physician assistants, pharmacists and other health careprofessionals interested in the treatment and management ofpatients with Myelodysplastic Syndromes.

LEARN ING OBJECT IVES� Describe the new WHO classification of MDS� Describe molecular features which are useful for classifying MDSand aiding in diagnosis and therapeutic decision-making

� Describe differences in therapy-related MDS which needconsideration for their treatment

� Describe immune-related mechanisms and treatment approachesfor patients with MDS

� Describe novel biologic approaches for treating anemiasassociated with MDS

FUND INGThis activity is jointly-provided by The Myelodysplastic SyndromesFoundation, Inc. and AKH Inc., Advancing Knowledge in Healthcare,Inc. This activity is supported by an educational grant from CelgeneCorporation and Onconova Therapeutics, Inc.

DON’T FORGET TO VISIT OUR MDS FOUNDATION BOOTH #3027 IN THE EXHIBIT HALL

Richard A. Larson, MDProfessor of MedicineUniversity of ChicagoChicago, IllinoisUwe Platzbecker, MDProfessor of HematologyUniversity Hospital Carl Gustav CarusDresden, GermanyDaniel T. Starczynowski, PhDAssociate ProfessorCincinnati Children’s Hospital Medical CenterCincinnati, Ohio

FACULTYStephen Nimer, MDSylvester Comprehensive Cancer CenterUniversity of MiamiRafael Bejar, MD, PhDAssistant ProfessorUniversity of California, San Diego Moores Cancer CenterLa Jolla, CaliforniaRobert Hasserjian, MDAssociate Professor of PathologyMassachusetts General Hospital and Harvard Medical SchoolBoston, Massachusetts

10

2017

Welcome to MDS 2017On behalf of the Scientific and Local Organizing Committees and the MDS Foundation, it is our pleasure to invite you to the 14th International Symposium on Myelodysplastic Syndromes taking place in Valencia, Spain from May 3-6, 2017. As in previous years, the Symposium will cover all relevant clinical aspects of MDS diagnosis, prognosis, and management as well as the newest data in MDS basic and translational research. The main lectures will be delivered by recognized international leaders but we also expect to include high-level research talks selected from the abstracts submitted by attendees. Further, we are very happy to

offer you the opportunity to visit Valencia, a city with a perfect combination of tradition and modernity. Located in the East of Spain, on the shores of the Mediterranean Sea, Valencia has a unique charm and is one of the cities in Europe that has experienced the most significant growth over recent years in terms of events and international recognition. This is due to the renovation of the historical city center and the creation of new cultural and environmental sites such as the City of Arts & Sciences and the Oceanographic Marine Park. Valencia has mild weather all year long with more than 300 days of sunshine per year, more than 20 km of beaches, a varied gastronomy and the home of the paella, and a Mediterranean way of life. The venue, the Valencia Conference Center, is a modern building designed by Norman Foster and is ideally located. It takes only 10 minutes to reach the historic city center (excellent links by metro, bus and tram), is only 5 km (10 minutes) from the international airport at Manises, and offers over 1,000 hotel rooms within walking distance.

We look forward to seeing you in Valencia!

Guillermo SanzSymposium Chair

Welcome to MDS 2017

2017

Guillermo Sanz


11

MAY 3-6 , 2017Valencia, Spain

THE 14TH INTERNATIONAL SYMPOSIUM ONMYELODYSPLASTIC SYNDROMES

Off SiteAuditorium 3Auditorium 2Auditorium 1Exhibition AreaTime

Workshop I - Cytometry

Alberto Orfao, Spain

Workshop IIGenetics

Francesc Solé, Spain

Workshop IIICytomorphology

John Bennett, USAJean Goasguen, France

Timothy Graubert, USA

Wednesday, May 3, 2017

legend:

12:00 - 14:00

Alberto Orfao, SpainyCytometr -

orkshop IW

orkshop IIW

18:30 - 20:00

16:00 - 18:00

14:00 - 16:00

clonal evolution in MDS • Clonal diversity and

eOpening Cer remony

Jean Goasguen, France

clonal evolution in MDS • Clonal diversity and

emony

John Bennett, USACytomorphology

orkshop IIIW

Francesc Solé, SpainGeneticsorkshop IIW

elcome Reception20:00 - 21:30

18:30 - 20:00

W

imothy Graubert, USA

elcome Reception

Tprogression

clonal evolution in MDS

imothy Graubert, USAprogression

clonal evolution in MDS

12




MDS biology and pathogenesis 1

08:30 MDS: a stem cell disorder Stephen D. Nimer, USA

08:50 - Driver and late occurring somatic mutationsElli Papaemmanuil, USA

09:10 - Epigenetic deregulationMaria E Figueroa, USA

09:30 - Oral Presentation



10:30 - Aging, CHIP, and MDS - David P. Steensma, USA

10:50 - The aberrant spliceosome machinerySeishi Ogawa, Japan

11:10 - Deregulation of the innate immune systemAlan F. List, USA

11:30 Oral Presentation


Diagnosis and prognosis of MDS / New challenges & new approaches

12:00 - 2016 WHO classification: main changesUlrich Germing, Germany

12:20 - Cytogenetics: still alive? - Francesc Solé, Spain12:40 - Somatic mutations: a role for improving diagnosis and risk assessment?Rafael Bejar, USA



13:45-15:15 Industry Supported session –

Pipeline Session not included in the CME/CPD

Program

Lunch Break, Exhibition &

Poster Viewing

Oral session 2Oral session 115:30 - 17:00

Thursday, May 4, 2017

07:30 - 08:30

08:30 - 10:00

Meet the Expert

09:10 - Epigenetic deregulation

Elli Papaemmanuil, USAsomatic mutations08:50 - Driver and late occurring

Stephen D. Nimer08:30 MDS: a stem cell disorder


Meet the Expert

09:10 - Epigenetic deregulation

Elli Papaemmanuil, USAsomatic mutations08:50 - Driver and late occurring

, USA r r, USA08:30 MDS: a stem cell disorder


Meet the Expert

Meet the Expert Meet the Expert

10:00 - 10:30

machiner10:50 - The aberrant spliceosome

. Steensma, USADavid P P. Steensma, USA10:30 - Aging, CHIP




Maria E Figueroa, USA09:10 - Epigenetic deregulation

offee Break, Exhibition & Poster V

10:50 - The aberrant spliceosome

. Steensma, USA, and MDS - IP P, and MDS -



C


Maria E Figueroa, USA09:10 - Epigenetic deregulation

iewingoffee Break, Exhibition & Poster V

10:30 - 12:00

main changes12:00 - 2016 WHO classification:

oachesapprroachesMDS / New challenges & new

o Diagnosis and pr rognosis of



. List, USAAlan F F. List, USAinnate immune system11:10 - Deregulation of the

Seishi Ogawa, Japanymachiner

12:00 - 2016 WHO classification:

MDS / New challenges & newognosis of



innate immune system11:10 - Deregulation of the

Seishi Ogawa, Japan


12:00 - 13:30



y Supported session –Industr13:45-15:15


, USARafael Bejar r, USAassessment?for improving diagnosis and risk12:40 - Somatic mutations: a roleFrancesc Solé, Spain12:20 - Cytogenetics: still alive? -

Ulrich Germing, Germanymain changes


y Supported session –13:45-15:15


for improving diagnosis and risk12:40 - Somatic mutations: a roleFrancesc Solé, Spain12:20 - Cytogenetics: still alive? -

Ulrich Germing, Germany

Poster V

17:00

17:00 - 17:30

- 15:30

13:30 - 15:30Lunch Break, Exhibition &

iewingProgram

Oral session 1

Poster V


not included in the CME/CPDPipeline Sessiony Supported session –Industr


Program

Oral session 1

C

Oral session 2

not included in the CME/CPDPipeline Sessiony Supported session –

iewing

Oral session 2


13



Nurse Session A

Biology and Management of CMML

17:30 - Relevance of flow cytometry, cytogenetics, somatic mutations, and epigenetic alterations in CMMLEric Solary, France

17:50 Risk assessment in CMML – Luca Malcovati, Italy

18:10 - Current management and investigational approachesEric Padron, USA



17:30 - 19:00

Nurse Session B

David Bowen, UK

TBA

Fabio Efficace, Italy

Maria E. Díez Campelo, Spain

Raphael Itzykson, France

Matteo G. Della Porta, Italy

Industry Supported session

not included in the CME/CPD Program

Industry Supportedsession

not included in the CME/CPD Program

Off SiteAuditorium 3 Auditorium 2Auditorium 1Exhibition AreaTime

legend:

19:00 - 17:30

Luca Malcovati, Italy17:50 Risk assessment in CMML –

, Franceyy Eric Solaralterations in CMMLmutations, and epigenetic

, cytogenetics, somaticycytometrry17:30 - Relevance of flow

CMMLBiology and Management of

Luca Malcovati, Italy17:50 Risk assessment in CMML –

, Francealterations in CMMLmutations, and epigenetic

, cytogenetics, somatic17:30 - Relevance of flow

Biology and Management of

Nurse Session A

19:20 - Prediction of azacitidine


Maria E. Díez Campelo, Spainlenalidomide benefit19:00 - Prediction of ESAs and

espon edicting r response to therPrre


Eric Padron, USAinvestigational approaches18:10 - Current management and

Luca Malcovati, Italy



Maria E. Díez Campelo, Spainlenalidomide benefit19:00 - Prediction of ESAs and

apynse to ther rapy

effectiveness analysis ofaspects and cost

y19:00 - Regulator

chOutcome Resear rchHealth Economics and


investigational approaches18:10 - Current management and

Luca Malcovati, Italy

effectiveness analysis of

chHealth Economics and

20:00 - 20:10

19:00 - 20:00

Matteo G. Della Porta, Italyoutcomes19:40 - Predicting transplantation

Raphael Itzykson, Francebenefit19:20 - Prediction of azacitidine

Matteo G. Della Porta, Italy

19:40 - Predicting transplantation

Raphael Itzykson, France


Fabio Efficace, ItalyOutcomes in MDS19:40 - Patient Reported

TBAMDS patients in USA

ost of care of19:20 - C

David Bowen, UKdrugs in Europeeffectiveness analysis of

Nurse Session B

Fabio Efficace, Italy

19:40 - Patient Reported

MDS patients in USAost of care of

effectiveness analysis of

20:10 - 21:10

CPD Programnot included in the CME/

sessiony SupportedIndustr


y Supported


sessiony SupportedIndustr

14




Singular subtypes of MDS08:30 - Insights into the mechanism of action of lenalidomide in patients with deletion 5qBenjamin Ebert, USA

08:50 - Clonal evolution in aplastic anemia and hypoplastic MDSGhulam J. Mufti, UK

09:10 - New developments in childhood MDSCharlotte M. Niemeyer, Netherlands



Therapy-1 Current options10:30 - How I treat MDS patients?Pierre Fenaux, France

10:50 - Management of MDS with 5q- after lenalidomide failureAristoteles Giagounidis, Germany

11:10 - Looking for the best partner for hypomethylating gents in higher-risk patients Mikkael Sekeres, USA



Therapy-2 New developments12:00 - Clinical trials in EuropeLionel Ades, France

12:20 - Clinical trials in USA Guillermo García-Manero, USA

12:40 - New agents for anemic patients: modified activin receptorsUwe Platzbecker, Germany



13:45-14:45Industry Supported session –

Pipeline Sessionnot included in the CME/CPD

Program

Friday, May 5, 2017

ime

07:30 - 08:30

T Exhibition Ar

ea

Meet the Expert

Benjamin Ebert, USAdeletion 5qlenalidomide in patients withmechanism of action of08:30 - Insights into theSingular subtypes of MDS

ibition Ar rea Auditorium 1

Auditorium 1

Benjamin Ebert, USA

Meet the Expert

lenalidomide in patients withmechanism of action of08:30 - Insights into theSingular subtypes of MDS

Meet the Expert

Auditorium 2

Auditorium 2

Meet the Expert Meet the Expert

Auditorium 3

f SiteOf

08:30 - 10:00



NetherlandsCharlotte M. Niemeyerchildhood MDS

developments in09:10 - New

Ghulam J. Mufti, UKMDSaplastic anemia and hypoplastic08:50 - Clonal evolution




, meyer r,

developments in

Ghulam J. Mufti, UK

aplastic anemia and hypoplasticin08:50 - Clonal evolution


10:00 - 10:30

10:30 - 12:00

partner for hypomethylating for the best Looking11:10 -

GermanyAristoteles Giagounidis,failurewith 5q- after lenalidomide 10:50 - Management of MDS

Pierre Fenaux, Francepatients?10:30 - How I treat MDS

ent optionsapy-1 CurrTher


partner for hypomethylating for the best

Aristoteles Giagounidis,

with 5q- after lenalidomide 10:50 - Management of MDS

Pierre Fenaux, France

10:30 - How I treat MDS ent options

C


Guillermo García-Manero, USA12:20 - Clinical trials in USA

Lionel Ades, France12:00 - Clinical trials in Europe

apy-2 New developmentsTher


Presentation11:30 - Oral

Mikkael Sekeres, USAgents in higher-risk patients partner for hypomethylating

Guillermo García-Manero, USA12:20 - Clinical trials in USA

Lionel Ades, France12:00 - Clinical trials in Europe

apy-2 New developments


Presentation

Mikkael Sekeres, USAgents in higher-risk patients partner for hypomethylating

& Poster V13:30-15:00

12:00-13:30

Lunch Break, Exhibition


Programiewing& Poster V

Lunch Break, Exhibition

not included in the CME/CPD Pipeline Sessiony Supported session – Industr

13:45-14:45


, Uwe Platzbecker r, Germanyreceptorspatients: modified activin 12:40 - New agents for anemic


Programnot included in the CME/CPD

Pipeline Sessiony Supported session –

13:45-14:45


, Germany

patients: modified activin 12:40 - New agents for anemic

15




Therapy-3 Allogeneic hematopoietic cell transplantation

15:00 - Candidates and timingTheo de Witte, The Netherlands

15:20 - Pre- and post-transplant strategies to reduce relapseCharles Craddock, UK

15:40 - New stem cell donor sources and regimens for transplantationDavid Valcarcel, Spain



Torsten Haferlach, Germany

Leonor Arenillas, Spain

Arturo Pereira, Spain

Norbert Gattermann, Germany

Valeria Santini, Italy

Fernando Ramos, Spain

Guided Poster Session

Palacio deCongresos de

Valencia (Room TBA)Auditorium 3Auditorium 2Auditorium 1Exhibition AreaTime

Patients Forum

Saturday, May 6, 2017

15:00 - 16:30

Charles Craddock, UKreduce relapsetransplant strategies to 15:20 - Pre- and post-

Netherlandsitte, TheTheo de W

timing15:00 - Candidates and

ansplantationtrhematopoietic cell

apy-3 Allogeneic Ther

Charles Craddock, UK

transplant strategies to 15:20 - Pre- and post-

itte, The

15:00 - Candidates and

hematopoietic cell apy-3 Allogeneic

16:30 - 17:00



with MDSCaring for the patient

C


alcarcel, SpainDavid Vtransplantationand regimens for cell donor sources 15:40 - New stem

iewing


Caring for the patient MDS

oversial issues in ontrC



alcarcel, Spain

and regimens for cell donor sources 15:40 - New stem

17:00 - 18:00

treatment decisiongeriatric assessment in index and comprehensive

omorbidity 17:40 - C

aleria Santini, ItalyVin MDS17:20 - Thrombocytopenia

GermanyNorbert Gattermann, new?MDS. Is there something 17:00 - Iron overload in with MDS

geriatric assessment in index and comprehensive

omorbidity

aleria Santini, Italy

17:20 - Thrombocytopenia

Norbert Gattermann,

MDS. Is there something 17:00 - Iron overload in

subtypes reduce life 17:40 - Do all MDS

Leonor Arenillas, Spainfor counting BM blastsappropriate denominator 17:20 - Choosing the

Germanyorsten Haferlach, TTorsten Haferlach,

currently available tools?diagnose MDS using 17:00 - How do I MDS

appropriate denominator

currently available tools?


20:00 - 22:30

18:00 – 19:15

Fernando Ramos, Spain


treatment decision

Fernando Ramos, Spaintreatment decision

Arturo Pereira, Spainexpectancy?

Networking Event

g EventNetworking Event

10:00 - 10:30

08:30 - 10:00

Oral session 3

offee Break

Oral session 3

C

Oral session 4

Patients Forum

12:00 - 12:30

10:30 - 12:00

Best Abstracts Session

farewell

Closing remarks and

Best Abstracts Session

farewell

Closing remarks and

16



Late/Onsite fee

From A pril 27, 2017

Regular fee

From March 7

until April 26, 2017

Early bird fee

until and including

March 6, 2017

FEES FOR ALL MEETING PARTIC IPANTS INCLUDE

Registration

MDSF member

MDSF member

March 6, 2017

550.00€

until and including

Early bird fee

550.00

March 6, 2017

650.00€

until and including

Early bird fee


From March 7

Regular fee

650.00


€

From March 7

Regular fee

pril 27, 2017From A

Late/Onsite fee

750.00

pril 27, 2017

Late/Onsite fee

Student**

orkshopMorphology W

Nurse**

Non member

150.00

orkshop 25.00€

200.00

€

650.00

€

€

150.00

25.00€

200.00

200.00€

650.00

250.00€

700.00€

200.00

25.00 €

250.00

€

700.00

€

€

225.00

40.00€

300.00

800.00

Networking Dinner

orkshop

orkshop

Genetics W

orkshop

y WFlow cytometr

Morphology W

orkshop

Networking Dinner 100.00€

orkshop

25.00€

orkshop

25.00€

25.00€

25.00

100.00 100.00€

25.00

€

25.00

€

€

25.00

100.00 €

25.00

€

25.00

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MDS Patient and Family Forum

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INTERNATIONAL WORKING GROUPSMDS FOUNDATION INTERNATIONAL WORKING GROUP FOR PROGNOSIS IN MDS

Latest News Regardingthe Molecular MutationProject of the IWG-PMMutations Predict PrognosisIndependent of the IPSS-R:Overview

The International Prognostic ScoringSystem (IPSS) and IPSS-R were developedby the International Working Group forPrognosis in MDS (IWG-PM) under theaegis of the MDS Foundation and havebecome the dominant clinical tools forpredicting prognosis in patients withmyelodysplastic syndromes (MDS).1 Aprognostic scoring system that integratesgene mutations into the known criticalclinical features would have great additiveutility for improved determination ofprognosis in patients with MDS and has thepotential for widespread clinical use. Theongoing project of the IWG-PM MolecularCommittee (IWG-PM-M) has shown, withthe IPSS-R and other scoring systems,using larger molecularly characterizeddatasets, that mutations are independentpredictors of patients’ overall survival.This finding justifies a prognostic scoringsystem that will integrate clinical andgenetic features.

Prognostic Impact of TP53Mutations

A central aim of the IWG-PMMolecular project is to develop a largedatabase of MDS patients with deepclinical annotation and genetic sequencingdata for clinical, biologic and possiblytherapeutic purposes. In addition to theanalysis of previous samples, sequencingadditional MDS cases will be performed tofurther develop the database.

As a first project for the IWG-PMmolecular database, the impact of TP53mutations in MDS demonstrated that this

status divides MDS patients with complexkaryotypes into distinct prognostic riskgroups, with those carrying the mutationhaving poorer prognoses. Despite theirstrong associations with adverse clinicaland cytogenetic abnormalities that arealready incorporated into existing prog-nostic scoring systems, TP53 mutationscarry significant independent prognosticvalue for decreased survival for patientswith MDS. This work was presented byDr. Rafael Bejar at the 2014 AmericanSociety of Hematology Meeting2 withupdating at the 2015 13th InternationalMDS Foundation Symposium held inWashington, D.C.

Recent Molecular ResultsRecently, molecular and clinical data on

3392 MDS patients gathered by membersof the IWG-PM-Molecular Committeewere combined and analysed and theabstract describing these findings waspresented for oral presentation at the recentASH Annual Meeting in Orlando.3Survival data were available for 3200patients. The 27 genes sequenced in at leasthalf of the cohort and mutated in >1.5% ofsamples were included for analysis.Mutations in 12 genes were stronglyassociated with shorter overall survival inunivariate analyses. The large size of thecohort allowed for more precise estimatesof survival in the less frequently mutatedgenes. IPSS-R risk groups could bedetermined for 2173 patients and were

strongly associated with survival. Adjustingthe hazard ratio of death for IPSS-R riskgroups identified several mutated geneswith independent prognostic significance.Patients without mutations in any of themajor adverse genes represented over halfof the fully sequenced cohort and had alonger median survival than patients withadverse mutations even after correction forIPSS-R risk groups. A mutation scorebased on survival risk will be proposed andinternally validated. The impact of somaticmutations in patients traditionallyconsidered lower risk will also be explored.

Current Project Status, Plans forsequencing of new samples

In addition to the above assessment ofprevious samples, led by Dr ElliPapaemmanuil, the project is sequencingadditional large numbers of MDS cases tofurther develop our database andmutational evaluations. An automatedsample management system was recentlyimplemented that links sample reception tolibrary preparation and sequencingsubmission. The results of these analyseswill serve as the template with which to buildan integrated molecular risk model for MDS.

References1. Greenberg PL, Tuechler H, Schanz J, et al.

Revised international prognostic scoringsystem for myelodysplastic syndromes.Blood. 2012;120:2454–2465.

2. Bejar R, Papaemmanuil E, Haferlach T,Garcia-Manero G, Maciejewski JP, SekeresMA, Walter MJ, Graubert TA, Cazzola M,Malcovati L, Campbell PJ, Ogawa S,Boultwood J, Bowen D, Tauro S, Groves M,Fontenay M, Shih L-Y, Tuechler H,Stevenson D, Neuberg D, Greenberg PL,Ebert BL. TP53 Mutation Status DividesMDS Patients with Complex Karyotypes intoDistinct Prognostic Risk Groups: Analysis ofCombined Datasets from the IWG-PM-Molecular Prognosis Committee. Proc AmSoc Hematology, San Francisco, December,2014, abstract, Blood. 2014;124 (21):#532.

3. Bejar R, Papaemmanuil E, Haferlach T,Garcia-Manero G, Maciejewski JP, SekeresMA, Walter MJ, Graubert TA, Cazzola M,Malcovati L, Campbell PJ, Ogawa S, FenauxP, Hellstrom-Lindberg, Kern W, Boultwood J,Pellagatti A, Bowen D, Tauro S, Groves M,Vyas P, Quek L, Nazha A, Thol F, Heuser M,

Dr. Peter Greenberg speaking at the IWG-PMmeeting during the 2015 ASH Congress.

Revised International PrognosticScoring System (IPSS-R) for

Myelodysplastic Syndromes

Risk Assessment Calculator

© MDS Foundation. All rights reserved.

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Shih L-Y, Padron E, Sallman D, Komrojki R,List A, Santini V, Fontenay M, Campbell P,Tuechler H, Stevenson D, Neuberg D,Greenberg P, Ebert BL. Somatic Mutations inMDS Patients Are Associated with ClinicalFeatures and Predict Prognosis Independentof the IPSS-R: Analysis of CombinedDatasets from the IWG-PM-MolecularCommittee, ASH 2015 abstract, Orlando,December 2015. Blood. 2015;126 (23), #907. IPSS-R Calculators

(Basic and Advanced)Available Online and

at the App Store

DOWNLOADOUR FREE APP

MDS FOUNDATION INTERNATIONAL WORKING GROUP FOR PROGNOSIS IN MDS

Myelodysplastic syndromes represent aheterogeneous group of disease entitieswith diverse clinical features, geneticcomposition, natural history, and responseto therapy. Mounting evidence hassuggested that several MDS ‘subtypes’ aredistinct enough that they should beconsidered unique disease entities. To thisend, in 2008 the World HealthOrganization designated four clinicalentities to be recognized as bona fidediseases with overlapping dysplastic andproliferative features. These includeChronic Myelomonocytic Leukemia(CMML), atypical CML (aCML), JuvenileMyelomonocytic Leukemia (JMML), andMyelodysplastic/MyeloproliferativeNeoplasms Unclassifiable (MDS/MPN-U).Since this reclassification, manyinvestigations have confirmed the uniquemolecular underpinnings and clinicaltrajectories of each of these diseases.However, this stratification has resulted inrare diseases that require collaborativeefforts to make transformative changes inpatient care.

The MDS/MPN International WorkingGroup (MDS/MPN IWG) was originallydeveloped in 2012. The work of this initialgroup resulted in the first two peer-

� Identify/Generating a consensus CMMLprognostic model.

� Exploring the role of transplant inmolecularly defined CMML subtypes.

� Implementing international clinicaltrials on both sides of the Atlantic.

References:1. Savona MR, et al. An international

consortium proposal of uniform responsecriteria for myelodysplastic/myeloprolif-erative neoplasms (MDS/MPN) in adults.Blood. 2105;125:1857-1865, doi:10.1182/blood-2014-10-607341.

2. Mughal TI, et al. An International MDS/MPN Working Group’s perspective andrecommendations on molecular pathogenesis,diagnosis and clinical characterization ofmyelodysplastic/myeloproliferative neo-plasms. Haematologica. 2105;100:1117–1130,doi:10.3324/haematol.2014.114660.

3. Padron E. et al. An international data set forCMML validates prognostic scoring systemsand demonstrates a need for novel prognos-tication strategies. Blood Cancer. 2015;5,e333, doi:10.1038/bcj.2015.53.

reviewed publications. By the end of 2013,membership was expanded to include aCMML multi center project, and the groupenlisted the support of the MDS Foundation.The overarching goal of this group is toidentify key knowledge gaps in the area ofMDS/MPNs and facilitate international,collaborative, translational science geared torapidly improve our understanding of thesefatal neoplasms. The current membershipincludes 32 investigators, from 20 centers,across 7 countries.

Work from collaborations within thisgroup has resulted in several peer-reviewedpublications:� A consensus recommendation for

response criteria that sets the foundationfor a common endpoint across manyMDS/MPN clinical trials.2

� A consensus review on the biology andclinical presentation of MDS/MPNs.2

� The development of an internationalCMML dataset that includes clinicaland molecular data.3

Ongoing collaborations underway include:� Expansion and prospective molecular

sequencing of the international CMMLdata set.

� Exploring the consequence of anMDS/MPN diagnosis on quality of life.

MAKING CONNECTIONS AROUND THE WORLD

The MDS/MPN International Working Group

This global project is being coordinatedby Ben Ebert and Peter Greenberg (co-Chairs), Rafael Bejar and ElliePapaemmanuil, with statistical supportby Donna Neuberg, Kristin Stevensonand Heinz Tuechler.

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Highlights of LatestLiterature in MDS Suneel D. Mundle, PhDRhea Mundle

Listed below are citations of some newpublications relevant to MDS (pathogenesis,clinical characterization, management, etc.).To access the complete articles log on towww.pubmed.gov.

EPIDEMIOLOGY, DIAGNOSISAND PROGNOSIS:1. Steensma DP et al. Connect MDS/AML:

Design of the myelodysplastic syndromesand acute myeloid leukemia diseaseregistry, a prospective observationalcohort study. BMC Cancer. 2016;16:652(https://www.ncbi.nlm.nih.gov/pubmed/27538433) The present report provides design of thefirst prospective non-interventionalobservational registry for MDS/AML thatwill enroll approximately 1500 USpatients from 150 community andacademic centers. The disease diagnosiswill be based on a central pathologicalreview and the study will include 4patient cohorts- lower risk MDS (low/int-1), higher risk MDS (int-2/high), AMLand ICUS (idiopathic cytopenia ofundetermined significance),

2. Arber DA et al. The 2016 revision to theWorld Health Organization classificationof myeloid neoplasms and acute leukemia.Blood. 2016;127(20):2391–2405. (https://www.ncbi.nlm.nih.gov/pubmed/27069254) Gene expression arrays and next-generation sequencing have brought tolight several new molecular biomarkersfor myeloid neoplasms especially in acuteleukemias. In light of this knowledge the2008 WHO classification is revised toreflect the consensus opinions of hemato-pathologists, hematologists, oncologistsand geneticists. The present articledetails major changes and specificrationale behind them.

3. Greenberg PL et al. Cytopenia levels foraiding establishment of the diagnosis ofmyelodysplastic syndromes. Blood. 2016

Aug 17 [Epub ahead of print] (https://www.ncbi.nlm.nih.gov/pubmed/27535995)This letter to editor provides clarificationon recently revised WHO criteriaregarding the thresholds to be used fordetermining milder cytopenia whendefinitive morphologic and/or cytogeneticfeatures of MDS are present. The authorsrecommend the use of standardhematologic values rather than the IPSSprognostic cutoff values to define suchcytopenias for the diagnosis of MDS.

4. Yao CY et al. Distinct mutation profileand prognostic relevance in patients withhypoplastic myelodysplastic syndromes(h-MDS). Oncotarget. 2016 Aug 4 [Epubahead of print] (https://www.ncbi.nlm.nih.gov/pubmed/27527853) In a series of 369 MDS patients classifiedper WHO 2008 criteria, 100 patients(approx. 27%) were diagnosed ashypocellular subtype. As compared tonormo-/hyper-cellular MDS cases, thesehypocellular patients tended to be lowerrisk with lower bone marrow andperipheral blood blast counts, hadsignificantly lower incidence of RUNX1,ASKL1, DNMT3, EZH2 and TP53mutations and demonstrated relativelylonger overall survival.

5. Pfeilstöcker M et al. Time-dependentchanges in mortality and transformationrisk in MDS. Blood. 2016;128(7):902–910(https://www.ncbi.nlm.nih.gov/pubmed/27335276) A retrospective study of 7212 primaryuntreated MDS cases from the IWGdatabase for prognosis in MDS, showedthat mortality and leukemic transformationrates diminished over time in higher riskpatients, while remained stable in lowerrisk patients with hazards in differentprognostic categories becoming similarafter approximately 3.5 years essentiallyreaching equivalence after 5 years.

6. Bennett JM et al. Dysplastic erythroidprecursors in the myelodysplasticsyndromes and the acute myeloidleukemias: is there biologic significance(How should blasts be counted?). LeukRes. 2016;47:63–69. (https://www.ncbi.nlm.nih.gov/pubmed/27258735)

A study of % erythroid precursors (EP)within bone marrow aspirate blast countfrom >1400 MDS patients enrolled inDusseldorf, Germany Adult MDS registry,showed no impact of % EP (including theFAB group’s recommendation of “50%rule”) on overall survival or leukemictransformation rates.

TREATMENT:Hypomethylating Agents:1. Thépot S et al. A randomized phase II

trial of azacitidine +/- epoetin-β in lower-risk myelodysplastic syndromes resistantto erythropoietic stimulating agents.Haematologica. 2016;101(8):918–925.(https://www.ncbi.nlm.nih.gov/pubmed/27229713) The study prospectively comparedoutcomes of lower risk MDS relapsing afteror refractory to ESA, if they were randomlytreated with azacitidine or azacitidine +epoietin-β. Among the 98 patientsrandomized 1:1, transfusion independencewas achieved after 6 cycles in comparablenumber of patients in both groups (approx.16% with azacitidine alone or 14% withcombination). So was the overall erythroidresponse similar in the two cohorts studied.

2. Zhang Z et al. increased PD-1/STAT1ratio may account for the survival benefitin decitabine therapy for lower risk myelo-dysplastic syndrome. Leuk Lymphoma.2016 Aug 11 [Epub ahead of print](https://www.ncbi.nlm.nih.gov/pubmed/27686004) Among the 44 lower risk MDS patientstreated with decitabine, 59.1% achievedoverall response, and 53.8% achievedreduction in PRBC/Platelet transfusionburden with a median overall survival of19 mo for the group. An increase in type1CD8+ population was noted andamplification of PD-1/STAT1 ratio of 2–4was associated with longer survival.

3. Zeidan A et al. Comparative clinicaleffectiveness of azacitidine versusdecitabine in older patients with myelo-dysplastic syndromes. Br J Haematol.2016 Sept 21 [Epub ahead of print](https://www.ncbi.nlm.nih.gov/pubmed/27650975)

MDS RESOURCES

(HR-3.3, p=0.005). Additionally thestudy also showed significantly lowerBFU-E, CFU-E and CFU-G/M in MDSthan normal bone marrows.

2. Obeng EA et al. Physiologic expressionof SF3B1 (K700E) causes impairederythropoiesis, aberrant splicing andsensitivity to therapeutic spliceosomemodulation. Cancer Cell. 2016;30(3):404–417 (https://www.ncbi.nlm.nih.gov/pubmed/27622333) SF3B1 mutations are frequent in MDSespecially in RARS patients. The presentstudy showed that introduction of aspecific high frequency mutation SF3B1(K700E) using a knockin mousetechnique, caused erythroid dysplasiaand macrocytic anemia. The spliceosomemodulator, E7017 selectively killed thecells expressing SF3B1 (K700E), whichmay have therapeutic implications.

3. Hilgendorf S et al. Loss of ASXL1triggers an apoptotic response in humanhematopoietic stem and progenitor cells.Exp Hematol. 2016, Sept 8 [Epub aheadof print] (https://www.ncbi.nlm.nih.gov/pubmed/27616637) ASXL1 is frequently mutated in MDS.Using a specific small interfering RNAtransduced in human cord blood CD34+cells, ASXL1 expression was knockeddown. This resulted in a significantreduction in myeloid stem cell number aswell as their expansion potential and inparticular caused apoptosis of erythroidprogenitors at all stages of differentiation.

REVIEWS, PERSPECTIVES & GUIDELINESThe following articles provide significantreview of literature and/or innovativeperspective on the state-of-the-art in MDSor discuss therapeutic management guide-lines and identify need for additionalprospective studies.1. Bigenwald C et al. Are myelodysplastic

syndromes and acute myeloid leukemiaoccurring during the course of lymphomaalways therapy related? Br J Haematol.2016 Sept 23 [Epub ahead of print](https://www.ncbi.nlm.nih.gov/pubmed/27662562)

patients assessed efficacy and safety oflenalidomide in non-del(5q) MDS. Theprimary end point of ≥8 wk transfusionindependence was achieved withlenalidomide treatment in 26.9% patientsvs. 2.5% on the placebo arm (p<0.001).The median duration of TI withlenalidomide was 30.9 wks. Additionally≥4 units reduction in PRBC transfusion at112 days assessment time point was seenin 22% with lenalidomide, compared tonone on the placebo arm. Neutropeniaand thrombocytopenia were the mostcommon adverse events.

Novel Therapies:1. Schuler MK et al. Effects of a home-

based exercise program on physicalcapacity and fatigue in patients with lowto intermediate risk myelodysplasticsyndrome- pilot study. Leuk Res. 2016;47:128–135 (https://www.ncbi.nlm.nih.gov/pubmed/27326698) A prospective non-randomized feasibilitystudy assessed evaluating safety andefficacy of home-based exerciseintervention to overcome fatigue andbuild physical capacity was a subject ofthe present report. In a strength andendurance building training, of 21 totalMDS patients, 15 (71%) continued onstudy till week 12 with 11 completing theprogram. Significant improvement in 6min-walking distance exercise was seen.However no improvement was noted infatigue scores.

PATHOBIOLOGY:1. Li B et al. Colony-forming unit cell

(CFU-C) assays at diagnosis: CFU-GMcluster predicts survival in myelodys-plastic syndrome patients independentlyof IPSS-R. Oncotarget. 2016 Sept 18[Epub ahead of print] (https://www.ncbi.nlm.nih.gov/pubmed/27655727) CFU-C assays of bone marrow samplesfrom 365 consecutive newly diagnosedMDS patients with a median survivalfollow up of 22 mo, in multivariateanalyses demonstrated that a cluster toCFU-G/M ratio of >0.6 was anindependent risk factor for overallsurvival after adjusting for IPSS-R

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The study identified patients diagnosedwith MDS between 2004-2011 in the USbased SEER registry, who received ≥10doses of either azacitidine or decitabine.With a median survival estimate of 15 mo(RAEB subset –12 mo), the study did notfind significant difference with respect tothe hypomethylating agent used (HR=1.06, p=0.37). A significantly shortersurvival was noted in the present studywith azacitidine treated RAEB patients ascompared to previously reported survivalfor the same MDS subset in AZA-001clinical study (11 mo vs. 24.5 mo,respectively).

4. Mittleman M et al. Azacitidine-lenalidomide (ViLen) combination yieldsa high response rate in higher risk myelo-dysplastic syndrome (MDS)-ViLen-01protocol. Ann Hematol. 2016; 95(11):1811–1818 (https://www.ncbi. nlm.nih.gov/pubmed/27546027) ViLen-01, a phase IIa study includedtreatment of high risk MDS with 6 monthinduction regimen of Azacitidine+lenalidomide followed by consolidationusing azacitidine and maintenance withlenalidomide. A total of 25 subjects withsignificant co-morbidities in 88% weretreated on the study (13 completinginduction, 7 entered consolidation and 2went into maintenance). Using IWGcriteria, the authors reported 72% (18/25)ORR, 24% (6/25) CR, 12% (3/25) marrowCR, 36% (9/25) HI, PFS and OS both 12mo. The safety profile was acceptablewithout any new signal for the combinationover the expected AEs for individual agents.

IMiDs:1. Santini V et al. Randomized phase III

study of lenalidomide versus placebo inRBC transfusion-dependent patients withlower-risk non-del(5q) myelodysplasticsyndromes and ineligible for or refractoryto erythropoiesis-stimulating agents.J Clin Oncol. 2016;34(25):2988–2996(https://www.ncbi.nlm.nih.gov/pubmed/27354480) A phase III randomized placebocontrolled double blind study with 239ESA refractory or ineligible lower risk

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2. Bhatt VR and Steensma DP. Hemato-poietic cell transplantation for myelo-dysplastic syndromes. J Oncol Pract.2016;12(9):786–792. (https://www.ncbi.nlm.nih.gov/pubmed/27621329)

3. Zeidan AM, Stahl M and Komrokji R.Emerging biologic therapies for thetreatment of myelodysplastic syndromes.Expert Opin Emerg Drugs. 2016;21(3):283–300 (https://www.ncbi.nlm.nih.gov/pubmed/27486848)

4. Platzbecker U and Fenaux P. Recentfrustration and innovation in myelo-dysplastic syndrome. Haematologica.2016;101(8):891–893 (https://www.ncbi.nlm.nih.gov/pubmed/27478197)

5. Navada SC and Silverman LR. The safetyand efficacy of rigosertib in the treatmentof myelodysplastic syndromes. ExpertRev Anticancer Ther. 2016;16(8):805–810 (https://www.ncbi.nlm.nih.gov/pubmed/27400247)

6. Malcovati L and Cazzola M. Recentadvances in the understanding ofmyelodysplastic syndromes with ringsideroblasts. Br J Haematol. 2016;174(6):847–858 (https://www.ncbi.nlm.nih.gov/pubmed/27391606)

We would like to thankSuneel Mundle, a member of the

MDS Foundation, andRhea Mundle for their assistancin monitoring these important

peer-review publications on MDS.

INTERNATIONAL BOARD OF DIRECTORSChairman Stephen D. Nimer, MD, USA

John M. Bennett, MD, USA

Mario Cazzola, MD, Italy

Erin P. Demakos, RN, CCRN, USA

Theo J.M. de Witte, MD, PhD, The Netherlands

Benjamin Ebert, MD, PhD, USA

Pierre Fenaux, MD, PhD, France

Peter L. Greenberg, MD, USA

Eva Hellström-Lindberg, MD, PhD, Sweden

Sandra E. Kurtin, RN, MS, AOCN, ANP-C, USA

Alan F. List, MD, USA

Silvia M. M. Magalhães, MD, PhD, Brazil

Yasushi Miyazaki, MD, Japan

Ghulam J. Mufti, DM, FRCP, FRCPath, UK

Charlotte M. Niemeyer, MD, Germany

Franz Schmalzl, MD, Austria (Emeritus)

Roberta Smith, CPA (Treasurer)

THE MYELODYSPLASTIC SYNDROMES FOUNDATION, INC.

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Who Are We?The Myelodysplastic Syndromes (MDS)Foundation, Inc. is an internationalorganization devoted to the support andeducation of patients and healthcareproviders in the fields of MDS and relatedmyeloid neoplasms in order to accelerateprogress leading to the control and cure ofthese diseases. By building an internationalcommunity of physicians, researchers, andpatients, we will make potentially curativetherapies available for all patients with MDS.

What is MDS?The myelodysplastic syndromes are a groupof bone marrow disorders resulting in theineffective production of normal matureblood cells. Many patients experienceanemia from the lack of effective red bloodcells, thereby requiring frequent bloodtransfusions. A shortage of white blood cellsmay cause malfunctioning of the immunesystem resulting in infections. Insufficientplatelets can result in excessive bleeding. Inabout one-third of MDS patients, the diseasetransforms into acute myelogenous leukemia(also known as AML).

What We DoThe MDS Foundation provides researchgrants for scientific investigators, sponsorsinternational working groups of scientistsand physicians to further diagnostic,prognostic and treatment techniques, anddisseminates information on state-of-the-art research, clinical trials and treatmentsamong the professional and patientcommunities. The Foundation also referspatients to its collection of “MDS Centersof Excellence,” maintains an electronicforum on its website for interaction andsupport among patients, and provideseducational programs for both healthcareprofessionals and patients and their families.

Where We AreThe Foundation is located in Yardville,New Jersey and is active in more than 35countries around the world. Our Board ofDirectors consists of physicians and

nurses actively engaged in searching for acure of the disease. Our Nurse LeadershipBoard is comprised of specialized nursessharing information and teaching othershow to care for MDS patients. Together,the Board of Directors and the NurseLeadership Board consists of 46 membersrepresenting 16 countries. Please see ourwebsite www.mds-foundation.org for acomplete list of our board members andother vital information about the diseaseand the Foundation.

Our FundraisingEffortsAs a tax exempt non-profit, section 501(c)3organization, donations to the MDSFoundation qualify for a U.S. tax deduction(it is essential to consult with your taxadvisor to confirm your own tax situation).The MDS Foundation actively seeksfinancial support for our mission andprograms to continue providing servicessuch as the following:� International Working Group for

Prognosis in MDS (IWG-PM)� Young Investigator Research Grants� Hot-line for patients and caregivers to

speak with our Patient Liaison at 800-MDS-0839

� Numerous Face to Face Patient Forumsin multiple cities with presentations bylocal physicians

� Online Patient Forum monitored byexperts

� Designation of Centers of Excellence(COE) meeting the highest standards fordiagnosis, treatment, and patient care

� Patient Referrals to COEs� Building Blocks of Hope © handbook (in

print or online) with complete writtenand video information on the care andtreatment of MDS

� The MDS News Email Alerts� Biennial International MDS Symposia

for professionals & continuing medicaland nursing education programs

Donations can be made on ourwebsite by credit card or bycheck made payable andaddressed to:

The MDS Foundation, Inc.4573 South Broad St.Suite 150Yardville, New Jersey 08620

www.mds-foundation.org

ABOUT THE MDS FOUNDATION

INTERNATIONAL MDS FOUNDATION NURSE LEADERSHIP BOARD

Erik Aerts, RNZürich, Switzerland

Angelika BitterStudy Coordinator/Nurse Dresden, Germany

Claudia Boglione, RNFlorence, Italy

Núria Borràs, RNBarcelona, Spain

Karen Campbell, RNEdinburgh, ScotlandUnited Kingdom

Hwang Chung Cheng JordanRN, MN, Adv DipSingapore

Nicole Crisp RN, BScN, MN, NP-adultEdmonton, Alberta, Canada

Erin Demakos, RN, CCRNNew York, New YorkUnited States

Rebecca Dring, RNMelbourne, Australia

Corien Eeltink, RN, MA ANPAmsterdam, The Netherlands

Lenn Fechter, RNStanford, CaliforniaUnited States

Janet Hayden, RN, BSc(hons), MPHLondon, United Kingdom

Miki Iizuka, RNKanagawa, Japan

Jacqueline Jagger, BA, RNGosford, Australia

Christiane KahleLead Study Coordinator/Nurse Dresden, Germany

(Continued) 24

MDS Manager:An mHealth Applicationfor Patient andCaregivers LIVING with MDSSandra Kurtin, RN, MS, AOCN, ANP-CNurse PractitionerThe University of Arizona Cancer CenterAssistant Professor of Clinical MedicineAdjunct Clinical Asst Prof of NursingPhD CandidateThe University of Arizona, Tucson, Arizona

Assisting patients and their caregiversto live with the highest quality of lifepossible despite the diagnosis of MDS isthe primary mission of The Myelodys-plastic Syndromes Foundation. Among themost recent educational initiatives is theBuilding Blocks of Hope®, a print and onlineinteractive resource aimed at empoweringpatients and caregivers living with MDS.1Book 5 of the Building Blocks of Hope® isfocused on staying well and taking an activepart in the management of MDS (Figure1). This is the inspiration for creating adigital tool, MDS Manager, aimed atexpanding resources for patients and care-givers LIVING with MDS (Figure 2). Livingwith a cancer, including MDS, requireslife-long learning to effectively mitigateadverse events and improve quality of life.Active involvement of the patient and theircaregivers in managing their health mayresult in extended survival.2 Engagementof the patient and their caregivers inexpressing their wishes, and taking a part inthe management of their health, includingengaging in health technology as a tool forhealth self-management is essential. Healthtechnology, including mHealth applications,offer expanding capabilities for engaginghealth consumers in health self-management.3However, despite the robust pace of mHealthdevelopment, empirical data specific tomHealth use in cancer survivors, particularlyolder adults, are limited.4 Therefore, cancerin the older adult, including MDS, willremain a predominant health care concernand strategies for health self-management

in this population, including mHealth tech-nology, require disciplined and systematicreview to guide ongoing research.5

Figure 2.

Book 1

UNDERSTANDING MDS

E

Figure 1. Building Blocks of Hope: Strategiesfor Patients & Caregivers LIVING with MDS

Mobile health applications provide thecapability for interactive, dynamic anduntethered technology to support healthself-management, however, their contentand interventional elements need to begrounded in human computer interfacedesign and health behavior andcommunication theory and practice.4,6-8

Being an informed consumer of healthinformation is the expected norm. The

Features Include:

MDS Profile includingtracking of blood countsMedical ProfessionalsClinical TrialsAdditional ResourcesSymptom TrackerMedicineCalendarNotesMDS

MANAGER

Emily A. Knight, RN, BSN, OCNScottsdale, ArizonaUnited States

Sandra E. Kurtin RN, MS, AOCN, ANP-CTucson, ArizonaUnited States

Petra Lindroos Kolqvist, RNGoteborg, Sweden

Arno Mank, RN, PhDAmsterdam, The Netherlands

R. Denise McAllisterMS, ARNP, AOCNPClearwater, FloridaUnited States

Cindy Murray, RN, MN, NP-adultToronto, OntarioCanada

Geke Ong, RNLondon, United Kingdom

Phyllis Paterson RN, RSCN, Dip OncCambridge, United Kingdom

Jean A. RidgewayMSN,APN, NP-C,AOCNChicago, IllinoisUnited States

Barbara A. Rodgers, RN, BSN, OCNSeattle, WashingtonUnited States

Jayshree Shah APN-C, AOCNP, RN, MSN, BSN, BS, CCRPHackensack, New JerseyUnited States

Natalie Singer, MSc, RN, BSc(Hons) Glasgow, ScotlandUnited Kingdom

Samantha Soggee, RN, MNHeidelberg, Victoria, Australia

Mary L. Thomas, RN, MS, AOCNPalo Alto, CaliforniaUnited States

Sara M. Tinsley, PhD, ARNP, AOCNTampa, FloridaUnited States

Catherine Vassili, RNVictoria, Australia

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average age of the MDS patient atdiagnosis to be 73 years, and the estimatedaverage life expectancy for individuals 75years of age to be more than 10 years(10.94 males; 12.76 females).9 Userinvolvement in design, particularly in theolder adult population, is a critical step inincreasing the probability of continued use,necessary for behavioral change. MDSManager (Figure 2) represents thesynthesis of the success of the BuildingBlocks of Hope®, experiential knowledge,and systematic review of the literaturerelative to mHealth applications, healthself-management and communicativehealth literacy.1,5,10,11 User input, withinclusion of MDS survivors and theircaregivers in pilot testing of MDS Managerhas recently been completed and will becritical to refinement of the applicationprior to launching the application to thegeneral MDS population.12 Findings fromthis study will be presented at the 14thInternational Symposia on Myelodys-plastic Syndromes to be held in Valencia,Spain. The refined MDS Manager will beintroduced at the 58th American Society ofHematology Meeting and Exposition to beheld in San Diego, California. MDSManager will be launched in early 2017,including a research study testing bidirec-tional communication tailored to theindividual MDS patient aimed at improvinghealth-self management, technologyengagement, communicative health literacyand clinical trials participation. MDSManager will be available on both Androidand IOS smartphones and tablets.The majority of care for the MDS patient

is provided in the outpatient setting, isepisodic, and relies heavily on the ability ofthe patient and their caregivers to managetheir care, report symptoms, and seekinformation to assist them in performingthese tasks.13 Therefore, it is imperative thatwe empower patients and caregivers to makeinformed choices about their care, track andreport symptoms, and develop the skills andknowledge to take an active part in theircare. MDS Manager provides an innovativetool that will assist patients and caregiversLIVING with MDS with the ability to keep

track of blood counts, treatments,symptoms, provider and caregiver infor-mation, link to resources and clinical trialsinformation, and is proposed to provide atangible and meaningful strategy forimproving health self-management.

References1. Kurtin S. Building Blocks of Hope: Strategies

for Patients and Caregivers LIVING with MDS.New Jersey: The Myelodysplastic SyndromesFoundation; 2012.

2. Jenerette CM, Mayer DK. Patient-ProviderCommunication: the Rise of Patient Engage-ment. Seminars in oncology nursing. 32(2):134–143.

3. Jawed SI, Myskowski PL, Horwitz S,Moskowitz A, Querfeld C. Primary cutaneous T-cell lymphoma (mycosis fungoides and Sezarysyndrome): part II. Prognosis, management, andfuture directions. Journal of the AmericanAcademy of Dermatology. 2014;70(2):223e221–217; quiz 240–222.

4. Bender MS, Choi J, Arai S, Paul SM, GonzalezP, Fukuoka Y. Digital technology ownership,usage, and factors predicting downloadinghealth apps among caucasian, filipino, korean,and latino americans: the digital link to healthsurvey. JMIR Mhealth Uhealth. 2014;2(4):e43.

5. Kurtin S. mHealth as a Means to Foster HealthSelf-Management in Older Adult CancerSurvivors. Unpublished work: The University ofArizona College of Nursing; 2016.

6. Nasi G, Cucciniello M, Guerrazzi C. The role ofmobile technologies in health care processes:the case of cancer supportive care. J MedInternet Res. 2015;17(2):e26.

7. Vollmer Dahlke D, Fair K, Hong YA, BeaudoinCE, Pulczinski J, Ory MG. Apps seekingtheories: results of a study on the use of healthbehavior change theories in cancer survivorshipmobile apps. JMIR Mhealth Uhealth.2015;3(1):e31.

8. Kurtin S. Specific Aims: Feasibility andusability of MDS Manager. Unpublished work:The University of Arizona College of Nursing;2016.

9. Cogle CR. Incidence and Burden of theMyelodysplastic Syndromes. Current hemato-logic malignancy reports. 2015;10(3):272-281.

10. Kurtin S. Testing and Design of a Mobile HealthApplication aimed at Self-Management. TheUniversity of Arizona College of Nursing; 2015.

11. Kurtin S. Evaluation of a Mobile HealthApplication Aimed at Self-Management. TheUniversity of Arizona College of Nursing; 2015.

12. Kurtin S. Usability pilot testing of a health andlife management mobile health application(mHealth App) for caregivers and patients livingwith Myelodysplastic Syndromes: The Universityof Arizona; 2016.

13. Kurtin S, Paterson P, Wintrich S, et al. Patientand family resources for living withmyelodysplastic syndromes. Clinical journal ofoncology nursing. 2012;16 Suppl:58–64.

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Cancer EpigeneticsDr. I.M. Bennani-BaitiPresident, Cancer Epigenetics Society Vienna, Austria

For many cancer patients, time is of theessence. Despite its promises, the field ofcancer epigenetics has been slow intranslating its findings into tangible clinicalapplications. For example, 5-azacytidine,an epigenetic drug shown to more thandouble survival of mice with leukemia in1964, and which showed a remarkableactivity in cancer patients in clinical trialsin 1975, was only in 2004 FDA-approvedfor the treatment of MDS, a cancer thatuntil then had no other treatment, 40 yearsafter its discovery! The Cancer EpigeneticsSociety is the official society for cancerepigenetics research whose goal is to speedup cancer epigenetics discovery and thetranslation of basic research into clinicalpractice. To do so, the Cancer EpigeneticsSociety is developing several tools and

resources, including several open-accessmedical and scientific databases, thusallowing researchers and clinical oncologistsaccess to cancer and epigenetics data at anunprecedented depth and speed. Ourdatabases and other resources also helpscientists generate soft lines of thinking bylooking at the broader picture of cancer-related processes that can otherwise not

readily be inferred from single articles. Inaddition, we have developed a publishingmodel that dramatically speeds up the timefrom research article submission topublication, while at the same timesignificantly increasing reproducibility,visibility, and impact. These measuresshould further help position the field ofcancer epigenetics as a leader in cancerinnovation and discovery. The CancerEpigenetics Society (https://ces.b2sg.org)offers free membership to physicians,scientists, and students, and is currentlyfunded only through charitable donationsfrom individuals.

NEWS FROM AROUND THE WORLD

Dr. Bennani-Baiti leads the efforts of theCancer Epigenetics Society.

TESTIMONIALS

“The MDS Foundation was very goodkeeping us up to date with informationon MDS.” My husband had it for many yearsand all of the possible treatments were done.Sadden to say I lost my husband after 53 1/2years of marriage. It happened this Feb. 2016.He was at home with me. I was the caregiverfor many years. It was heart wrenchingmany times, sometimes happy good newstimes. ALL memories ones worth keepingand to always cherish forever. Thank youagain MDS for helping me to comprehenda bit better the health issue. – Kathryn H.

“My daughter was excited to find yourwebpage and show it to me.” My sister(she is 84) and I (I’m 77 and have MDS)watched the 3 minute Building Blocks ofHope video. I would very much like to receiveone of the hard copy binders mentioned. Iam currently undergoing chemo and receivingblood transfusions and feel like we havemore questions than answers. I need all thehope I can get. Plus, it is difficult to get mysister and other family members to under-stand the symptoms (fatigue, anemia, etc.),seriousness of my condition (neutropenia,

“I simply wanted to say, afterreading your main page, that it wasextremely well written andinformative” It was direct withoutbeing alarmist, seemed quite fair in notexploiting data or attempting to useincomplete or partial research to furtheryour cause (therefore making what youDO SAY much more trustworthy), andexplained in very accessible termseverything one might want to know ona first investigation. Well done towhoever put this together! – Bill P.

“Thank you so much for all of yourkind words of encouragement and allof the helpful information you havesent.” This journey has a bright lightfor me and with people like you I knowit will be alright. – Rachel M.

“Thank you for all you do for thisorphan disease.” – Bob M.

“Just diagnosed and find yourwebsite excellent” – Edgar K.

This program is designed to give patients andcaregivers the in depth information that theyare looking for and to allow them to take anactive part in their MDS journey. The BBoHis available in several languages.

FROM THE FOUNDATION

Dr. Bennani-Baiti is hoping to draw the attention of MDS researchersto CES to spark new research ideasand new lines of inquiries into MDS. He is the President of CES, but he alsohas a personal connection to MDS –

his father is an MDS patient.

need for regular transfusions). Thank you foryour website and for sending me a copy ofyour handbook. – Donald G.

“The German version of Building Blocks ofHope brochure arrived today – many,many thanks. It is an amazing collectionof useful information”– Andy A.

“My father-in-law was just diagnosedwith MDS. I came across your websiteand am living with the wealth ofinformation I have gathered already.” I believe these books will be a wonderfulsource of guidance. Thank you!!! – Celena O.

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LATIN-AMERICAN GROUP FORMYELODYSPLASTIC SYNDROMES• The Latin-American Group for Myelo-dysplastic Syndromes (GLAM) is amulti-disciplinary group integrated byhealth professionals with a common aim:study MDS from pathogenesis throughclinical and therapeutic approaches.

• GLAM is evaluating the state-of-the-artof Myelodysplastic Syndromes (MDS)in the region to recognize strengths anddrawbacks in order to improve andencourage local actions.

• This group was created in close relation-ship with different Latin-AmericanSocieties of Hematology in considerationof their own regulations and interests.

Objectives• Contribute to progress in hematology,specifically in the field of MDS.

• Encourage scientific networking withother societies.

• Promote scientific and clinical research.• Collaborate with national and regionalhealth authorities.

• Develop local diagnostic and therapeuticguidelines and protocols.

• Organize continuous medical education(CME).

• Provide useful information for patientsand healthcare givers.

Team• GLAM includes various professionals likebiochemists, immunologists, cytogenetists,flowcytometrists, pathologists and hema-tologists. This diversity will contribute tobroaden complementary visions.

• To date, the group is integrated by 155colleagues from Latin America: Argentina,Bolivia, Brasil, Chile, Colombia, CostaRica, Dominican Republic, Ecuador, ElSalvador, Guatemala, Mexico, Panama,Paraguay, Peru, Uruguay and Venezuela.

ProjectsMDS SurveyThis survey aims to collect epidemiologicdata in order to know the state-of-the-art ofdiagnostic and therapeutic tools in the region.Training and TeachingOne of the most important projects is toorganize scientific MDS meetings, work-shops, symposiums, etc. in different LatinAmerican countries.MDS Common RegistryIt is extremely necessary to develop a LatinAmerican online MDS Registry in order tobuild a common database.SubcommitteesSmall and specialized working groupspromote the participation and exchange ofprofessionals’ experiences. The followingsubcommittees are proposed: 1–Diagnostic,2–Therapeutic strategies, 3–PediatricMDS, 4–Hematopoietic Progenitor CellTransplantation, 5–Secondary MDS, 6–Overlap syndromes.Investigation and Clinical TrialsWe are determined to encourageinvestigation and help to promote clinicaltrials in MDS throughout Latin America.Patients, Relatives and HealthcareGivers Information and SupportGLAM´s web page will provide usefulinformation about MDS to help groups ofpatients, relatives and healthcare givers.

GLAM

CONTACT [email protected]

Uruguayan Society of Hematology(on behalf of GLAM)COLONIA 1086 OF.404Montevideo, Uruguay

NEWS FROM AROUND THE WORLD

28

MyelodysplasticSyndromes – Just aMatter of Age?

Carolien M Woolthuis1

and Christopher Y Park2

1Human Oncology and PathogenesisProgram, Memorial Sloan KetteringCancer Center, New York, New York,US; 2Departments of Pathology andLaboratory Medicine, Memorial SloanKettering Cancer Center, New York,New York, US

The myelodysplastic syndromes (MDS)represent a heterogeneous group of clonalhematologic disorders, characterized byinefficient hematopoiesis, myeloiddysplasia, and an increased risk fordeveloping acute myeloid leukemia(AML).1,2 In the majority of patients,morbidity and mortality are the result ofprogressive cytopenias, but transformationto AML is observed in approximately one-

AbstractThe myelodysplastic syndromes

(MDS) are primarily a disease of theelderly, but it is unclear whether agingitself is an independent contributor tothe pathophysiology of these disorders.While the normal aged hematopoieticsystem and MDS share many featurescompared to young hematopoiesis, theyalso exhibit important differences. Withthe demonstration that mutations presentin MDS can also be identified in healthyelderly individuals, it will be importantto elucidate the differences andinteractions between normal hemato-poietic aging and MDS.

third of patients. MDS is highly associatedwith age, illustrated by an increase in theincidence with advancing age and a medianage at diagnosis of 65–70 years.

While the pathophysiology of MDS isnot fully understood, it is clear that itinvolves a multifactorial process thatincludes alterations in chromosomes, genemutations, and changes in DNAmethylation status in the hematopoieticcells.1,2 Recent large-scale genome-sequencing studies have identified multiplerecurrent gene mutations in MDS. Thesemutations affect genes involved inepigenetic regulation (e.g. DNMT3A,TET2, IDH1/2, EZH2, ASXL1)3 and RNAsplicing (e.g. SF3B1, SRSF2, U2AF1,ZRSR2)4,5 among other pathways. In themajority of MDS cases more than onemutation can be detected.6–8

Since MDS occurs primarily in elderlypatients, it has been hypothesized thathematopoietic aging itself is an importantfactor in the pathophysiology of MDS.Indeed, hematopoietic stem cells (HSCs) innormal aged individuals and MDS patientsexhibit similar differences when comparedto normal young adults, including anincreased frequency, myeloid skewing withdiminished lymphoid potential, anddecreased erythroid output.9–11

However, whether age simply increasesthe probability of acquiring diseaseinitiating mutations or whether cellularcontext itself contributes to diseasepathogenesis is an unresolved question.Interest in this question has increaseddramatically due to recent descriptions ofclonal hematopoiesis in healthy elderlyindividuals. While the phenomenon of age-related clonal skewing in the bone marrowhas been known for some time, the recentdevelopment of high-throughput genomesequencing has extended this observationby identifying presumed disease-initiatingmutations in healthy individuals.12–16

Indeed, the spectrum of mutations found inhealthy elderly individuals with clonalhematopoiesis overlaps considerably withthe mutations observed in MDS patients at

diagnosis, including DNMT3A, TET2, andASXL1 mutations. Blood-specific clonalmutations were identified in 5–6% ofhealthy people aged 70 years or older inone study16 and clonal hematopoiesis wasobserved in 10% of individuals aged 65and older in another cohort.13 Thedetection of a clonal mutation is associatedwith an increased risk for developing ahematologic malignancy. However, themajority of individuals with a detectableclonal mutation did not develop ahematologic disease and actually died fromnon-hematologic causes.13,14

This highlights the fact that the presenceof a somatic clonal mutation is distinctfrom a diagnosis of MDS. In fact, itresembles more a condition likemonoclonal gammopathy of undeterminedsignificance (MGUS) , which is associatedwith increased risk of developing clinicallyrelevant B-cell lymphoproliferations.Based on these insights it was recentlyproposed that in patients without hemato-logic alterations, detection of a clonalmutation in a gene also recurrently mutatedin hematologic malignancies could beclassified as a separate entity, termedclonal hematopoiesis of indeterminatepotential (CHIP).17 This would recognizethis condition while preventing over-diagnosis and misinterpretation. It wouldalso facilitate investigating the clinicalmeaning of detecting such mutations in theblood of a healthy person.17,18

CHIP arises when genetic alterationsare acquired in HSCs, much like MDS.While previous studies in MDSdemonstrated their HSC origin by showingthat chromosomal abnormalities associatedwith disease (i.e. loss of 5q, 7 or gain ofchromosome 8) are present inHSCs,10,11,19–22 a more recent studydemonstrated that MDS-associatedmutations in SF3B1 are present in HSCs.23

As previously described, there are severalsimilarities between hematopoiesis inaging and MDS. However, there are alsoimportant differences. For instance, bonemarrow dysplasia is not significant in

IN THE NEWS

The following article was published byTouch Medical Media within the Oncology& Hematology Review (US) Spring edition2016. The full edition is available at:

http://www.touchoncology.com/journals/editions/oncology-hematology-review-

volume-12-issue-1-spring-2016

29

healthy elderly and ineffective hemato-poiesis only occurs in the context of MDS.In addition, normal elderly and MDSpatients demonstrate differences inhematopoietic progenitor composition aswell as HSC gene expression profiles andDNA methylation.11 Whether such differ-ences are also present in CHIP HSCs whencompared with elderly HSCs is an openquestion that will likely be the subject offuture investigations.Given that normal aged HSCs and MDS

HSCs exhibit significant differences, someinvestigators have explored whether thesedifferences might be due to alterations inthe bone marrow microenvironment.24Although several recent studies haverevealed that bone marrow stromal cellsmay functionally interact with malignantmarrow cells to promote diseasephenotypes and that cell-intrinsic changesin stromal cells may induce MDS-likedisease,25–27 more studies are required toelucidate whether aging is involved inthese processes. In addition, investigatingwhether the presence of a mutation in ayoung or aged HSC results in the samehematopoietic phenotype would providesignificant insights regarding theimportance of the cellular context in whichsomatic mutations appear.Overall, multiple recent studies have

highlighted the differences betweenhematopoiesis in normal aging and MDS.The latter process clearly requires morethan just age-related alterations, of whichthe specifics are currently being elucidated,and therefore now, the line between normalhematopoietic aging and MDS is largely adistinction based on clinical features.Given the significant overlap betweenthese two states, finding features that arespecific to each would be an attractivefocus of future studies. A potential fruitfulapproach may be the evaluation ofpediatric, nonfamilial MDS, which wouldallow researchers to distinguish betweenage- and disease-related alterations. Inaddition, to more directly address thecontribution of aging to MDS pathogenesis,it will be important to use geneticallyaccurate disease models, which may be

induced at different ages to directly assessthe influence of cellular age on diseasecharacteristics. As such investigations arecurrently ongoing in various laboratories,we look forward to the results of thesestudies in the near future.

References1. Ades L, Itzykson R, Fenaux P, Myelo-dysplastic syndromes, Lancet, 2014;383:2239–52.

2. Tefferi A, Vardiman JW, Myelodysplasticsyndromes, N Engl J Med, 2009;361:1872–85.

3. Shih AH, Abdel-Wahab O, Patel JP, et al.,The role of mutations in epigeneticregulators in myeloid malignancies, Nat RevCancer, 2012;12:599–612.

4. Papaemmanuil E, Cazzola M, Boultwood J,et al., Somatic SF3B1 mutation inmyelodysplasia with ring sideroblasts, NEngl J Med, 2011;365:1384–95.

5. Yoshida K, Sanada M, Shiraishi Y, et al.,Frequent pathway mutations of splicingmachinery in myelodysplasia, Nature,2011;478:64–9.

6. Haferlach T, Nagata Y, Grossmann V, et al.,Landscape of genetic lesions in 944 patientswith myelodysplastic syndromes, Leukemia,2014;28:241–7.

7. Bejar R, Stevenson K, Bdel-Wahab O, et al.,Clinical effect of point mutations inmyelodysplastic syndromes, N Engl J Med,2011;364:2496–506.

8. Papaemmanuil E, Gerstung M, Malcovati L,et al., Clinical and biological implicationsof driver mutations in myelodysplasticsyndromes, Blood, 2013;122:3616–27.

9. Beerman I, Maloney WJ, Weissmann IL, etal., Stem cells and the aging hematopoieticsystem, Curr Opin Immunol, 2010;22:500–6.

10. Pang WW, Pluvinage JV, Price EA, et al.,Hematopoietic stem cell and progenitor cellmechanisms in myelodysplastic syndromes,Proc Natl Acad Sci USA, 2013;110: 3011–6.

11. Will B, Zhou L, Vogler TO, et al., Stemand progenitor cells in myelodysplasticsyndromes show aberrant stage-specificexpansion and harbor genetic and epigeneticalterations, Blood, 2012;120:2076–86.

12. Busque L, Patel JP, Figueroa ME, et al.,Recurrent somatic TET2 mutations innormal elderly individuals with clonalhematopoiesis, Nat Genet, 2012;44:1179–81.

13. Genovese G, Kahler AK, Handsaker RE, etal., Clonal hematopoiesis and blood-cancerrisk inferred from blood DNA sequence, NEngl J Med, 2014;371:2477–87.

14. Jaiswal S, Fontanillas P, Flannick J, et al.,Age-related clonal hematopoiesis associatedwith adverse outcomes, N Engl J Med,2014;371:2488–98.

15. Shlush LI, Zandi S, Mitchell A, et al.,Identification of preleukaemic haematopoieticstem cells in acute leukaemia, Nature,2014;506:328–33.

16. Xie M, Lu C, Wang J, et al., Age-relatedmutations associated with clonalhematopoietic expansion and malignancies,Nat Med, 2014;20:1472–8.

17. Steensma DP, Bejar R, Jaiswal S, et al.,Clonal hematopoiesis of indeterminatepotential and its distinction from myelo-dysplastic syndromes, Blood, 2015; 126:9–16.

18. Malcovati L, Cazzola M, The shadowlandsof MDS: idiopathic cytopenias of unde-termined significance (ICUS) and clonalhematopoiesis of indeterminate potential(CHIP), Hematology Am Soc Hematol EducProgram, 2015;2015:299–307.

19. Nilsson L, Strand-Grundstrom I, ArvidssonI, et al., Isolation and characterization ofhematopoietic progenitor/stem cells in5q-deleted myelodysplastic syndromes:evidence for involvement at the hemato-poietic stem cell level, Blood, 2000;96:2012–21.

20. Nilsson L, Strand-Grundstrom I, AndersonK, et al., Involvement and functionalimpairment of the CD34(+)CD38(-)Thy-1(+) hematopoietic stem cell pool inmyelodysplastic syndromes with trisomy 8,Blood, 2002;100:259–67.

21. Tehranchi R, Woll PS, Anderson K, et al.,Persistent malignant stem cells in del(5q)myelodysplasia in remission, N Engl J Med,2010;363:1025–37.

22. Woll PS, Kjallquist U, Chowdhury O, et al.,Myelodysplastic syndromes are propagatedby rare and distinct human cancer stem cellsin vivo, Cancer Cell, 2014;25:794–808.

23. Mian SA, Rouault-Pierre K, Smith AE, etal., SF3B1 mutant MDS initiating cells mayarise from the haematopoietic stem cellcompartment, Nat Commun, 2015;6:10004.

24. Nakamura-Ishizu A, Suda T, Aging of thehematopoietic stem cells niche, Int JHematol, 2014;100:317–25.

25. Bulycheva E, Rauner M, Medyouf H, et al.,Myelodysplasia is in the niche: novelconcepts and emerging therapies, Leukemia,2015;29:259–68.

26. Cogle CR, Saki N, Khodadi E, et al., Bonemarrow niche in the myelodysplasticsyndromes, Leuk Res, 2015;39:1020–7.

27. Krause DS, Scadden DT, A hostel for thehostile: the bone marrow niche inhematologic neoplasms, Haematologica,2015;100:1376–87.

IN THE NEWS

MARK YOUR CALENDAR FOR THE LOCATION NEAREST YOU!FEBRUARY 25in honor of Rare Disease DayLas Vegas, NVGainesville, FL

APRIL 22Chicago, ILSeattle, WA

MAY 6Valencia, Spain

SEPTEMBER 9Buffalo, NYCharleston, SC

OCTOBER 28in honor of MDS World Awareness DayAtlanta, GASan Francisco, CA

NOVEMBER 18San Antonio, TXIowa City, IA

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PATIENTS & CAREGIVERS LIVING WITH MDS FORUMS2014 RARE DISEASE DAYSPREADING THE NEWS WORLDWIDE

LEARN MORE AT:www.mds-foundation.org/patient-and-family-forumsMany patients and caregivers have never met another person diagnosed with MDS until they connected with them at one of our forums. Ifyou’ve never attended one before, you won’t want to miss this opportunity to meet others and to learn more about MDS, current treatments,and emerging therapies from leading experts. Not only will you find answers, support and hope for MDS but you will learn tips andstrategies for patients and caregivers LIVING with MDS.

JUNE 11, 2016Copenhagen, DenmarkTHANK YOU to Prof. Drs. Lars Kjeldsen, Kirsten Grønbaek, and Lone Friis, for the invaluable contribution you all made at ourCopenhagen Patient Forum. From the feedback we’ve received, the program was a great success. We appreciate the time that you took outof your busy schedules to join us and thank you for sharing your insights and expertise with our attendees. Your willingness to volunteeryour time, energy and support on behalf of patients and caregivers living with MDS is greatly appreciated!

For our Danish speaking friends, the audio/visual taping of this event can be viewed herehttp://www.mds-foundation.org/mds-patient-forum-copenhagen-denmark

Register TodayFOR OUR FREE EVENTS

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RUNNING FOR AWARENESS Timothy Stohner ran the Naperville,

Illinois Half-Marathon in memory of hisfather to help raise awareness about MDSand the MDS Foundation. He feels fortunateto have the opportunity to run this race andhe encourages others to do the same.

2014 RARE DISEASE DAYWORKING TOGETHER FOR MDS

MDS FUNDRAISING EVENTS

COMEDY NIGHT IN MEMORY OFKAREN A. WENZEL

Karen A. Wenzel was a beloved wifeand mother who lost her battle with MDSin 2006. Karen’s son, Paul, has held manygolf tournaments in her memory but thisyear decided to plan a special comedy nightto support the MDS Foundation. Paul’shope is that this comedy event will be thefirst of many and will be a day to get familyand friends together to remember hismother, and to help raise money andawareness for MDS.

MDS AWARENESS T-SHIRTS Amber Cornell created MDS Awareness

T-shirts in honor of her grandfather, RichardPratt, who had MDS. He was her hero andbest friend. All proceeds from the sale weredonated to the MDSF.

Paul Wenzel with his mom, Karen

Tom ‘Shu’ Shuey

TOM “SHU” SHUEY MEMORIALGOLF TOURNAMENT

In memory of his Dad, Timothy Shueyand his family held their second annualcharity golf tournament on August 5. TomShuey passed away in 2014 after battlingMDS.

He was an avid golfer and his son,Tim’s biggest regret was missing his lastopportunity to golf with him. This inspiredTim and his family to organize an annualgolf tournament in his memory.

For years tocome, they planto keep Shu’smemory in ourhearts and minds,and continue tosupport the MDSFoundation.#2forshu

Tim using hisdad’s golf club

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BENEFIT CONCERTIn memory of her father, Anthony,

Janna Pelle organized her second MDSAwareness & Benefit Concert with theLeave A Lasting Mark Concert Series at theBitter End in New York City. This year’stheme was the Talking Heads album, “StopMaking Sense”— because MDS doesn’tmake sense. Hopefully, with our dedicatedwork, research, awareness and fundraising,we will be able to make sense of thisdisease and find better treatments for thefuture. There was also a bone marrow drivemade possible by Love, Hope, Strength atthe concert. With over 20 performingartists participating, including herself,money was raised to support the MDSF.

ASHLEY PANEI MDS AWARENESS WALK

Ashley was just 29 when she passedaway from MDS, and in lieu of flowers, thefamily asked that memorial contributions bemade to the MDS Foundation. She was inremission from having ovarian cancer whenshe was diagnosed with MDS and needed abone marrow transplant. Unfortunately, thedisorder took her life before she was able toget the transplant. In Ashley’s honor, herfamily will hold an annual walk in hermemory to benefit the MDSF.

FUN RUNTerry Tintor and her friends

participated in the ‘Light theNight’ LLS Walk and woreMDS T-shirts that they createdto increase MDS awareness.


MARIELLE THORSEN AND ERIC HALL WEDDING On June 2, 2015, Marielle lost her grandmother, Irene Caso, to MDS. In lieu of favors at their wedding on July 29, 2016, her husband,

Eric, and she donated to the MDS Foundation in honor and loving memory of her grandma. Marielle told us that she was the most beautiful,happiest, strongest, and above all, the most loving person in the world. Her husband and she were so happy to be able to include hergrandmother in their wedding by donating to the MDS Foundation. “She was definitely with us on our wedding day, it was the most beautifulday; sun was bright and shining, warm air, and overall just perfect and best day ever. We hope that our donations will help to find a cure andfurther research for MDS.”


DAN LEWIS MEMORIAL GOLF DAY Sue Lewis shares her husband’s journey with MDS.

We didn’t know how much our lives would changeon August 23, 2015. My husband, Danny, had just hadbloodwork done in order to have his prescriptionsrefilled. When the results came back, the doctorscalled and told us we needed to meet with them.

At our appointment on 8/23/2015, we were toldthat Dan had MDS. She suggested we meet with a

hematology/ oncology specialist in Pittsburgh instead of our doctor here in Pymatumy. Oncein Pittsburgh, they started the first round of chemotherapy. We then returned home tocomplete treatment in Meadville. Meanwhile, the doctors suggested we start testing familymembers for a bone marrow match. My brother-in-law was a suitable candidate. Theyordered a biopsy which now sadly indicated that Dan’s condition had progressed to leukemia.A ten day regiment of a much stronger dose of chemotherapy began. During this treatment,Danny developed an infection. The infection ultimately took his life on December 14, 2015.

Danny was a loving husband, a father offour (Dan, Jamie, Brandon, and a baby whichthey lost). He was a beloved son to Mary andTom and a brother to Debbie, Diane, Dale,Donny, Duane, and Denise. He was a friendto many. Dan was a dedicated worker atWestinghouse/Siemens for 40 years. Heloved hunting, fishing and any other outdooractivity. He definitely enjoyed a good beer!

T-SHIRT FUNDRAISER FROM LOVING DAUGHTER In memory of her Dad, Lee Kaasa, CaitlinWohlmacher designed MDS Awareness t-shirts with all monies raised donated to theMDSF. Read Caitlin’s dedication to her father.

My father was a family man that wasdevoted to taking care of those he loved. Heloved children and animals and was an avid

outdoorsman. His two most cherished hobbies were hunting andfishing. He also enjoyed target practice, mushroom picking,reloading his ammunition and working on his ‘29 Durant classiccar. He sadly passed away from complications brought on by MDSin February of this year.

As a welder and rigger, my father worked in the shipyardsaround the Puget Sound for 42 years. One of his many jobs was toclean out cargo ships after they had transported crude oil. Onechemical contained in crude oil is benzene. Sadly, the protectionfrom benzene for workers exposed to it was mostly non-existent inthe past, and contact would often burn their eyes and skin. Benzeneis a known trigger for MDS. It was this benzene exposure thatpossibly contributed to my father’s death.

My dad was never one to go to the doctor and due to this we didn’tknow he even had MDS. It had probably been developing for quite

some time and the onset was slowenough that we chalked it up togetting older. Eventually, he hadfallen too ill for it to be dismissed asaging. He was admitted to thehospital and bone marrow biopsiesled to the detection of MDS. He wasadmitted 3 different times over thecourse of a month and would receive plasma infusions, platelets, bloodtransfusions and 24 hour a day dialysis treatment. In his final stay at thehospital, he was placed on a breathing tube after contractingpneumonia. My father was, and always had been, one to never give up;a big tough guy with a teddy bear heart. Alas, he took his last ventureinto the woods and passed away at 6:10 pm on February 16, 2016. Hewouldn’t have wanted us to stress, worry, or be distraught; but whenyou love someone with everything you have you grieve in the deepestway possible. I still cry almost every day and will never forget what hashappened. As a father, husband, brother and grandfather, he was takenfrom us due to possible negligent safety practices in the workplace. Myfather will be missed and always in our hearts. We all cherish thememories of our loved ones and when they pass those memoriesbecome even more of a treasure.

Although he was a quiet man, you knewhe meant business when he spoke up.

We chose to honor Dan at our golfouting on July 16, 2016. All that attendedlaughed and enjoyed the memories whichwere shared. This is what Danny wouldhave wanted to be remembered with asmile, or in his case a smirk with a raisedeyebrow over the edge of his glasses!Although we lost him way too early, hewill forever be in our hearts.

We decided to make a donation to MDSwith the profits from our golf outing so thatmore people are aware of this conditionand research can only continue to improvetreatment.

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34


Shelly Guzek organ-ized her second annualATV wheeler ride andmud run on September 16in memory of her son,Taylor Moen, who passedaway October 26, 2014.

Taylor loved to ride 4-wheelers evenduring his struggle with MDS. Shellywants to continue this event as an annualtradition adding some humor and makingthis a unique ride to give Taylor some goodlaughs up in heaven and for any of thosewho have lost a loved one to MDS.

ATV ‘TRASH THE DRESS FOR MDS’ BENEFIT IN MEMORY OF TAYLOR MOEN

MDS JOURNEY TO HOPE BRACELETS

Look for more news as we get closerto the movie’s release date now slatedfor January 2017. Yale Productions,the makers of this film, will bedonating 5% of their campaign’sdonations, and 5% of the film’sproceeds to the MDS Foundation.

A CHRISTMAS MOVIEABOUT LOVE, FAITH,

FAMILY, ANDDEALING WITH MDS

Taylor

Sandy Madrigal handcrafted herbracelets to draw attention to MDS. Herdesigns are dedicated to the lovingmemories of her mother, Betty and hersister, Linda. They were diagnosed withMDS just eight weeks apart. Both foughtthe disease bravely and with great dignity.Now she is doing what she can to continuetheir fight. Each bracelet is only $20.00(plus S&H). A portion of the proceeds aredonated to the MDS Foundation.Women’s Bracelet: Swarovski crystals,fine glass beads, antique Rhodium (a lead-free pewter), silver plated and sterlingsilver accents. Men’s Bracelet: Wooden and organicbeads, silver plated accents and your choiceof “HOPE” or “MDS” sterling block letters.

Order your bracelets at:http://www.lovinkissescreations.com/mds.html

Women’s BraceletAvailable in: Petite (7 inches),

Small (7.25 inches, Medium (7.5 inches),Large (7.75 inches), and X-Large (8 inches)

Men’s BraceletAvailable in:

7 inches, 8 inches

35

We are very grateful to families and friends of MDS patients who make generous donationsin memory of their loved ones. We applaud all for your valiant efforts. THANK YOU SO MUCH!

Our work as a non-profit organization depends on public funding.If you would like to contribute in this way,

or if you have a unique idea of your own, please contact us.

REUBEN KINCAID RememberedDave Madden, the comedian and actor perhaps best known as ReubenKincaid in The Partridge Family, passed away in January of 2014 after a five-year struggle with MDS.

An accomplished magician and musician, Dave enjoyed almost fourteenyears of retirement before developing MDS. In this revised, edited, andupdated edition of Reuben on Wry, Dave’s wife, writer Sandra Madden,included a final chapter devoted to Dave’s MDS journey. Thank you, Sandra!

Each purchase of Reuben Kincaid Rememberedwill support the work of the MDS Foundation.


COOKBOOKS TO BENEFIT THE MDS FOUNDATION

Nancy Cosenza Nussbaum was looking for a way to pay tribute to her late sister, Ann Cosenza Hallberg, who passed away from MDS.As a result, she decided to publish a cookbook with recipes from family and friends, local restaurants, and some well-known bakers andchefs. For Nancy, continuing charitable work in her sister’s name allows others to know her and become aware of MDS.

NEW! Annie’s Sweet Tooth – Volume 2 – Now Available!

Thank you to Nancy Nussbaum for providing Volume 2 of Annie’sSweet Tooth and other savory delights! This edition is also dedicated tothe memory of Nancy’s sister, Ann Cosenza Hallberg.

Each cookbook is available for $10.00 + $3.00 shipping and handlingand 100% of the proceeds are donated to the MDS Foundation. Don’tmiss out on the new collection of recipes and cooking tips – order yourcopy today!

To order, email Janice Butchko at [email protected] or call 1.800.MDS.0839.

Annie’sSweet Tooth

and othersavory delights

Volume 2

Available through Amazon at:http://www.amazon.com/Reuben-Kincaid-Remembered-Memoir-Madden/dp/1517676223.

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Update: MeetingMackenzie’s DonorJoanne CurranKingston, Ontario, Canada

Last spring we shared with you thejourney of our daughter being diagnosedwith MDS, then receiving a successful bonemarrow transplant. We also shared that thispast December we learned the identity ofher unrelated donor, Alex from Germany.He was 23 at the time he said “yes” todonate his marrow stem cells to saveMackenzie’s life. In January we invited himto visit Canada and were thrilled when heaccepted our invitation.

How do we put into words the emotionswe felt on May 18, 2016 when, exactly 2 ½years after Mackenzie’s bone marrowtransplant, we were finally able to meetAlex, the young man who selflessly savedher life?

At 4:30 pm, friends, family, friends fromCanadian Blood Services, friends fromMake-A-Wish Eastern Ontario, and newsanchors watched, cheered, applauded andcried while Alex came down the escalator atthe Ottawa Airport in Ontario, Canada.Mackenzie ran to him. The meeting betweenAlex and Mackenzie was very emotional.

We were next in line to embrace andthank Alex, who was instantly welcomedinto our family. The day following thisindescribable meeting, our family wasinvited to Parliament Hill in Ottawa to meetthe Prime Minister which was an amazinghonor. We were given a personal tour ofParliament Hill. Prime Minister JustinTrudeau thanked Alex personally for his giftof life.

Alex spent two weeks with our family.We made sure he was able to see some of thepopular landmarks close to our home townof Kingston, Ontario. In addition to seeingParliament Hill in Ottawa, his visit included:a cruise of the 1000 Islands, lunch and a tourof the CN Tower, a visit to Ripley’sAquarium in Toronto, a Carrie Underwoodconcert in Toronto, a visit to Niagara Falls,and finally a bi-plane ride over Ottawa.

During the two weeks Alex spent inCanada, he was asked often and was able toshare with many, how simple the surgicalstem cell donation actually was. He leteveryone know he was asleep for theprocedure and left the hospital the very nextday – never requiring the pain medication hewas given.

It was difficult to say goodbye to Alexafter the 2 wonderful weeks we spent withhim, but thanks to modern technology weare able to keep in touch. One day we hopeto travel to Germany to visit Alex and hisfamily, and to thank his parents for raisingsuch a remarkable young man.

November 20, 2016 marked Mackenzie’s3rd bone marrow birthday. We celebrated thisday as we do every day. We will forever begrateful to Alex for his gift of life.

If you are interested in viewing thewonderful meeting between Mackenzie andAlex, please feel free to google: “CTV Ottawa– Mackenzie meets bone marrow donor”.

AML CORNER: A PEDIATRIC STORY

Parliament Hill: Prime Minister Justin Trudeau thanked Alex personally for his gift of life.

AML CORNER

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Fighting The BeastSandra AsherSan Antonio, Texas

It wasn’t supposed to turn out this way.My strong, smart, handsome, motorcycleriding, Krav Maga trained, “never beensick” husband Mike is fighting for his life.In retirement, we should be exploring newplaces, learning about new things andenjoying new experiences after a lifetimeof hard work. Going to see new doctors,learning about MDS and experiencing theyo-yo existence after diagnosis is not whatwe had in mind.

MDS is a beast. It has a vicious appetiteand prefers sneaking up behind unsuspectingvictims. The beast often disguises itself assomething else and seems to take pleasure inconfusing patient and doctor alike bycausing different kinds of problems andwasting precious time until it shows enoughof itself that a diagnosis can be made. Afterdiagnosis it continues its cruel path, pickingand choosing which victims will get more ofits attention. MDS toys with many of itsvictims for years, playing with them like ayo-yo. Other times it prefers to suck the lifeout of someone quickly.

My husband, Mike, is a retired, 21 year AirForce pilot. We raised a family while movingaround the country and were lucky enough tolive and travel in Europe for 5 years.During the last years of his career, he wasDeputy Commander of Basic Training forthe U.S. Air Force which brought us to SanAntonio, Texas. Lovely town, great Mexicanfood —we decided to stay after re tirement.

Mike worked at a second career inmanagement before retiring again. Hebecame a volunteer in the Burn Unit atBrooke Army Medical Center and joined thePatriot Guard, providing security andmotorcycle escort for our fallen militaryheroes. I continued my accounting day joband evenings as a fitness instructor withMike as my roadie and unpaid assistant. Heand I taught ballroom dance and loved totravel when my work would allow. Then Ihad a moderate brain stem stroke, followedsix months later by breast cancer. Mike was

with me every step of the way, throughrehab, treatments and surgeries. He tookcare of everything so I could concentrateon getting well. When the worst was finallyover, we were ready to get back on trackand start crossing things off our post-retirement bucket list. Instead, Mikecollapsed, unresponsive in an elevator onhis way to his volunteer job.

After a week of hospitalization, testsand consultations, we heard, “You havehigh risk MDS and have 1.6 years to live.There’s no cure.” WHAT? No, that can’t beright, Mike has never been sick in his life.He doesn’t even get colds. All of Mike’srelatives on both sides live into their 80’sand 90’s. It’s not fair! He should have 20more years. How can he be dying? Thebeast had found a new victim.

Our oncologist called in a colleague whoran the Bone Marrow Transplant Unit. Hetold us only about 10–15% of patients couldqualify for a transplant, but he had reviewedthe medical records and although Mike was68, his extraordinary good health and lackof comorbidities meant he could be a goodcandidate. There was a glimmer of hope.His MDS was an aggressive type so thedoctors wanted to get him to transplantwithin 3 months. We began a whirlwind oftests and evaluations. Mike said everydoctor in the hospital had to sign off on thetransplant except for OB/GYN! Mike askedme to be the detail person and his researchassistant so I needed to know as much aboutMDS as possible…fast. I found good, solid,up to the minute information on the MDSFoundation website. They sent me somehelpful resources like 100 Questions &Answers About Myelodysplastic Syndromes.The more I learned, the less afraid and moreconfident I became that Mike might beatthe beast.

The search for a donor began. Friends allover the country got cheek swabs. The idealdonor is 18–44 years old so fellow Chi Phifraternity alumni at Georgia Tech set up avery successful Be The Match event for thefraternities and sororities on campus. Hisstory was published in the national fraternityjournal, educating and inspiring otherchapters in the country to set up their ownevents. The doctors told us that there is onlya 20–25% chance that a sibling (no olderthan 60) will be a match. Mike had a betterchance finding an unrelated donor. He hasone sibling, a 60 year old sister who decidedto give it a try anyway. Her blood was drawnin Indiana where she lived and Fed Ex’d toour Texas doctors. She was a perfect 10/10HLA match!! Lisa unselfishly came to SanAntonio for more testing, preparation anddonation of 8 million healthy stem cells.(Once frozen, they are viable for 10 years!)

Meanwhile, Mike began chemo. He wasone of the lucky ones for whom Vidazaworked right away. The transplant was puton hold as long as the monthly chemo kepthim stable. He had virtually no side effectsand went through 13 cycles before the

AML CORNER: OUR CAREGIVER STORY

38

routine bone marrow biopsy showed theblast percentage had more than doubled!The doctor said it was important to havethe transplant in the next 30 days becauseMDS at that stage can progress quickly. Wewere given 50/50 odds of making itthrough the year but were sure he would beone of the survivors.

The transplant went fine. Mike had asore throat for two days…that’s it! He wentto the transplant unit gym most days, had anappetite and felt good. After a month he wasreleased. His numbers climbed steadily, allgetting into the normal range. We werethrilled! Mike had beaten the odds.

Around day +80 Mike’s plateletsstarted falling. In spite of medicationchanges, every few days. The lab resultsfor the other two cell lines began to fall too.Chimerism testing showed he had droppedfrom 93% donor at day +58 to 23% donor.The transplant had failed.

Failed? How could that be possible?Everything was in his favor. His siblingmatch was perfect. He was in goodphysical shape going into the transplant. Imade sure his nutrition and hisenvironment were perfect. He never had afever or infection. We followed ourdoctor’s advice in every way. We dideverything “right.” It should have worked.I guess we forget about the 50-50 odds.

The bone marrow biopsy had more badnews. The MDS had relapsed. His blastpercentage was the same as it had beenbefore the transplant. I poured my brokenheart out to others on the Facebook supportgroup, and searched online for news aboutpeople who had survived a relapse. Thebeast was back.

The doctors decided to try DLI (DonorLeukocyte Infusion), even though thechances of it working for a MDS patientare only about 30%. We were told acuteGVHD was likely. Mike had a round ofVidaza first, standard before DLI.Although he’d never had problems in 13prior rounds, this time his belly wasbruised and sore, he felt awful, and his labnumbers kept falling. New tests showedthat in less than a month, he had progressedto AML. The DLI was cancelled and thedoctor said anything done at this pointwould be a Hail Mary. He wouldn’t survivea second transplant. Mike was dying andthere was nothing more they could do.Disbelief, anger, sadness, depression…wewent through those and more.

Our doctor called a friend at MDAnderson Cancer Center in Houston andasked him to review the medical records.Could Mike qualify for a research trial?Although we were afraid of being told noand having our fragile hopes dashed again,we drove to Houston. After 10 days of testshe was accepted into a Phase I trial. He wasgiven “salvage” chemo, meant to try torescue patients with a poor prognosis andalso began the research trial oral chemo. Icould only see him through a window forweeks while he was in a protectiveenvironment. He got through the chemobut developed a serious complicationcalled paralytic ileus that almost killedhim. Not being able to touch him or evenbe close to him was awful, especially since

he was in so much pain. The MD Andersondoctors saved his life. Mike doesn’tremember most of that time, which is justas well. Thin and weak, he began torecover and could soon sit up if helped.

We spent 69 days at MD Anderson.Mike was 203 lbs when we arrived and 143lbs when we left last week. For the nextfour months, we will go back one week amonth for 4–5 days of inpatient chemo. Hetakes oral research trial chemo every dayalong with 11 other meds and is monitored3 days a week at our local hospital for labtests, blood, platelets, etc. Unless he is tootired, he can stand and shuffle along with awalker most days. Sometimes I have to pickhim up after a fall. He has no fat or muscleleft and is frustrated that he can’t open amedicine bottle. But he is glad to be aliveand has new hope because the last bonemarrow biopsy showed he is in remission!Of course we know the beast could comeback again, but for today, it’s gone and weare daring to think about a future.

No, this isn’t the way life was supposedto be at this stage of our lives. I neverdreamed Mike would be in the fight of hislife and I would be his full time caretaker.Thanks to my husband’s care two yearsago, I am physically able to take care ofhim now. We meant it 46 years ago whenwe promised “for better and for worse… insickness and in health.” Mike says we willdance again and I think I believe him.

Keep Calm and Get Educated

AML CORNER: OUR CAREGIVER STORY

39

Celgene and AgiosAnnounce CollaborationsWith Abbott ForDiagnostic Identificationof IDH Mutations in AMLSUMMIT, NJ and Cambridge, Mass. (Oct. 12, 2016) – Celgene Corporation(NASDAQ: CELG) and Agios Pharmaceuticals,Inc. (NASDAQ:AGIO) today announced eachcompany has entered into collaborationagreements with Abbott (NYSE: ABT), a leaderin diagnostic technologies, to develop andcommercialize companion diagnostic tests onAbbott’s m2000 RealTime System to identifyisocitrate dehydrogenase (IDH) mutations inacute myeloid leukemia (AML) patients. Celgeneis currently developing enasidenib (AG-221/CC-90007), an IDH2 mutant inhibitor, for thetreatment of patients with relapsed or refractoryAML who have an IDH2 mutation. Agios isdeveloping AG-120, an IDH1 mutant inhibitor,for the treatment of patients with relapsed orrefractory AML who have an IDH1 mutation.

IDH1 and IDH2 mutations occur inapproximately 20% of AML patients. An articlepublished online this week in the journalLeukemia (Medeiros, Leukemia 2016)concluded that advances in the understanding ofthe genetics underlying myeloid malignanciesare driving an era of development for targetedtreatments such as IDH mutant inhibitors. Theauthors recommend that IDH mutationalanalysis should become part of the routine AMLdiagnostic workup and repeated at relapse toidentify patients who may be eligible fortargeted investigational treatments currentlyunder clinical study.

“AML is a complex and heterogeneousdisease, making it difficult to treat,” said HanMyint, MD, Vice President, Global MedicalAffairs, Myeloid for Celgene. “IDH mutationslead to aberrant DNA methylation, causing ablock in myeloid differentiation that leads todisease progression. Molecular profiling isimportant to identify genomic mutations whichmay have prognostic and potential treatmentimplications for patients with AML.”

Abbott’s m2000rt RealTime System, is apolymerase chain reaction (PCR) instrumentdesigned to enable clinical laboratories toautomate PCR and results analysis, simplifyingthe complex and manual steps often associatedwith molecular diagnostics. Both Celgene and

Agios have incorporated thisscreening into clinical trialdesigns, including the recentlyinitiated Phase 3 IDHENTIFYtrial comparing enasidenib withconventional therapy in olderpatients with an IDH2 mutationand relapsed or refractory AML(NCT02577406).

“The field of personalizedmedicine is advancing at a rapidpace for a broad range of medicalconditions, especially withinhematology-oncology,” saidChris Bowden, MD, chiefmedical officer at Agios. “Ourcollaboration with Abbott willprovide a test to help identifyAML patients with IDH muta-tions who are in need of treatmentoptions.”

The m2000 system has notbeen FDA cleared or approved foruse with enasidenib or AG-120.

Enasidenib and AG-120 havenot been approved for any use inany country.

AML CORNER: PRESS RELEASE

www.heretohelpmds.com

The MDS Alliance would like to thank Celgene and Novartis for their support.

www.heretohelpmds.comwww.heretohelpmds.comwww.heretohelpmds.com

The MDS Alliance would like to thank Celgene and Novartis for their support.The MDS Alliance would like to thank Celgene and Novartis for their support.The MDS Alliance would like to thank Celgene and Novartis for their support.

That’s a remarkable milestone for aperson with two kinds of cancer.Estelle was diagnosed with MDS(myelodysplastic syndromes) andsmoldering multiple myeloma in late2011. What’s also remarkable is thatthere are cancer medications gentleenough for even a patient in her 90’s totolerate.

As Estelle herself has said, “I amamazed that I can take a drug thataffects my system. That I’m sosensitive to. Pretty great.”

Estelle now lives in San Franciscoso she can be near her grandson and hisfamily. She has had a difficult personallife with the loss of her husband andtheir two daughters, and in recentweeks she has slowed downconsiderably. But Estelle likes to say,

“It’s hard some days to say hoop de la,everything is great. There are a lot ofnegatives. But the positives outweighthe negatives — and you have torecognize them. I’m lucky to be here.”

This picture of Estelle was taken inFebruary of this year.

MDS Patient Celebrates herMilestone 100 Year Birthday

Estelle celebrated her 100th birthday September 30th!

40

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41

42

The MDS Family:Coping and Caring EventsRochelle Ostroff-WeinbergWynnewood, Pennsylvania

Coping and Caring LuncheonWhite Dog CaféPhiladelphia, PA, April 16, 2016

Have you felt overwhelmed by thedemands of your MDS? Are you alwaysfaced with low stamina and high worry overwhat medication might restore your energyand health? Have you felt overwhelmed thatMDS has taken over your life? And perhapsyou are confused by the advice offered?These core concerns, too, were articulatedby the MDS patients present. As each MDSpatient at the table recounted a grippinglyunique story, those voices and those storiesembody common elements understood andembraced by every MDS patient.

Have you ever felt that everyone aroundyou is focused on the unquestionablyimportant needs of your spouse, strickenwith MDS, leaving you in a lonely spot?Have you felt both helpless and hopeless asyou try to cope with your life that hassuddenly been metamorphosed into aworld of complex medical demands,questions and concerns? Do you feel guiltyif you express your needs, your fears andsense of overwhelmedness to others? Thesefeelings that are expressed by so manyspouses of MDS patients were clearly

heard around the table at this Coping andCaring White Dog luncheon event.

As we gathered at the table in anintimate setting at the White Dog Café,tenseness dissolved as folks began to feelcomfortable opening up their hearts to theMDS community assembled to listen,understand and share. I sensed that it wasthe first time that Prue, eyes welling withemotion, had been given the opportunity toexpress to someone the challenges for her,as she carries the responsibilities of theMDS spouse. This poignant momentunderscores the raison d’être of the Copingand Caring events.

The attendees represented a cross-section of the MDS Community:

Jeff and spouse Amy, regulars at theCoping and Caring events since itsinception three years ago, experience theability to breathe more easily than the othersthanks to a successful bone marrowtransplant. Jeff and Amy brought to the tablehope and a unique empathy. They told theirsuccess story to hungry and appreciative

ears. Both Amy and Jeff brought abeautifully special level of compassion tothe table. We all surely beam in learning thiswonderful detail, which Amy shared:

“Jeff’s donor, Nicole, and her familyvisited us to celebrate the fifth anniversaryof Jeff’s bone marrow transplant!”

Ray and spouse Prue, both in theireighties, are courageously walking theMDS path at this point in their lives. Pruecame to the table with an anxiety that Irecognized all too well. Ray’s attendanceat the luncheon enabled him to providecritical MDS information — videos,websites — to Claudette and George,creating an important bond that resultsfrom gathering together at the Coping andCaring table. It is quite simply moving towitness the patient to patient, spouse tospouse outreach that takes place at eachCoping and Caring event. Ray’s desire tohelp another MDS patient jumps out at you,conveying the invaluable benefit ofparticipation. Surely, it is not solely theconcrete information exchanged, but anMDS patient or spouse learning that she,that he is not alone with the MDS challenge.

Claudette and spouse George attendedfor the first time, contributing their feelingsand concerns. Of course, as they opened upto those gathered around them, what theyexpress bears fruit: understanding,empathy and support. Claudette shared:

“The people present were so welcomingwhich made it easier to get involved in thediscussion. I learned that MDS comes inmany different forms, that educatingoneself is important, and that MDS is notan immediate death sentence but requirestime and attention. I was made aware of theavailability of support groups, videos, andthe MDS Foundation who provides muchinformation. I learned so much from all ofyou. It is comforting to know that othershave similar problems but are unselfishlywilling to give support to others.”

Continuing around the table, we cometo Mindy Greenstein, author, nationalspeaker and psychologist, who was theperfect guest presenter at this event, I amso grateful to Audrey Hassan of the MDS

OUR CAREGIVER STORIES

COPING AND CARING

43

Foundation for her dedicated energy to findoutstanding presenters for each Coping andCaring event. And what exactly makesMindy an ideal choice? Along with thecredentials already mentioned, she is apsycho-oncologist and specialist ingeriatric psychiatry at Memorial Sloan-Kettering in New York, who brought to thetable a plateful of personal experiencesgermane to the situation of those inattendance, as well as deep knowledge andinspiring humanity. Each participantreceived a copy of her fascinating book,Lighter as We Go: Virtues, CharacterStrengths, and Aging (written inconjunction with Dr. Jimmie Holland). Iwas curious to learn her observations ofwhat unfolded at the event. Here is some ofwhat she shared:

“One theme from the book that seemed tohave resonance is the way we learn from ourexperiences and gain in emotional strengthover time. In my work, we help peoplerecognize and build on their strengths to dealwith adversity. The stories help me see thatkind of resilience at work in real time,watching participants support each other bysharing the lessons they’ve learned fromtheir own experiences. It was so hearteningto hear everyone’s stories, and see how muchsupport they provide each other. Eachstory—whether patient’s or familymember’s — is unique and yet, together, theyspeak to the vicissitudes of human resilienceand how much we gain from each other.”

Truly, who can be more genuinelyunderstanding of the circumstances, thetrauma or euphoria of those in the MDSCommunity than those who are living inthe same reality? And it is they who canbest benefit from hearing stories thatreplicate what they and what you are livingand experiencing each and every day.

Coping and Caring DinnerMargate, NJ, July 30, 2016

We gathered once again for the Copingand Caring dinner in Margate, New Jersey.And Audrey Hassan found, once again, aterrific guest presenter, Jill Garaffa, who,as Audrey described, offered “an inter-

active and engaging program”. As anoccupational therapist, professional certifiedlife coach and energy leadership masterpractitioner, Jill lent her knowledge oncoping with the challenges of living day today with this new normal – called MDS.

I want to thank everyone for making thevoyage to my summer home in Margate. Itwas unquestionably a significant momentfor me. I have given much reflection, sinceyour departure, to all that you shared: yourconcerns and worries, your hopes andrevelations. They gave and continue to giveme pause.

I was struck poignantly by Pat, yourremark that “nobody cares.” That crying outis resonating in every red blood cell in mybody, in every part of me. I heard that, as Ihope all of us did, long after we separated.As I said in immediate response “I care.”And I meant and I mean that with genuinefeeling and sincerity. I so hope that you feeljust a little bit less alone with this scaryreality. Please let me say again, I care.

There is also, please note, a photo ofBob, my husband, in the hospital a fewweeks before he died. Attached to his towerof infusions he is dancing to the music ofthe blues group, Muddy Waters. May thissnapshot linger in your mind, may it be aninspiration to you to get up and dance, toget up and exercise, to get up and to stay upand to know that I, Rochelle Ostroff-Weinberg, am holding you up.

I am a Fred and Ginger fan. In spite of“silly” scenes and “silly” songs, there isbrilliant wisdom to the messages behind


the fun. Here are some of the lyrics of oneof my favs that is my mantra:from SwingtimeJerome Kern and Dorothy Fields

...Nothing’s impossible, I have found.For when my chin is on the ground,I pick myself up, dust myself off,Start all over again.Don’t lose your confidence if you slip.Be grateful for a pleasant trip,And pick yourself up; dust yourself off;Start all over again...Will you remember the famous menWho had to fall to rise again.So take a deep breath;Pick yourself up; Dust yourself off;Start all over again.

Sending love and caring, Rochelle

44

My Dad, My HeroLisa EvangelistaLaguna Hills, California

When I think about how my dad shouldhave passed away, I think of him lying in ahospice bed, my mom, my sister and me athis side holding his hand. We would tellhim we’re so proud of him. He would sayhe’s proud of us. He would smile calmly atus before taking his last breath, squeeze mymom’s hand one last time and then gopeacefully to where we cannot follow him.That’s how I wished it had happened.

Flashback to over 25 years ago whenmy sister and I were young childrengrowing up in Canada. Our dad seemedlike a man of Herculean strength who couldpull both of us around in our toboggans inthe snow with one hand. He ran like astallion alongside us when he taught ushow to bike without training wheels. Hehad so much athletic prowess when heplayed basketball with us, we wished wecould be as good as him when we grew up.

We relocated to the United Statesshortly before our teenage years at whichtime we developed a vague awareness ofthe generic maladies that perturbed ourparents like hypertension and arthritis. Ourdad wasn’t Hercules anymore but mostpeople our parents’ age dealt with the sameafflictions so it was “normal.” In ourcollege years, our dad was diagnosed withlupus and his overall health seemed todecline.

It wasn’t until 2013 after a series ofabnormal blood test results and a bonemarrow biopsy that our dad’s healthseemed to actively take a different course.He was diagnosed with myelodysplasticsyndromes or MDS for short. Afterbecoming familiar with the condition, webegan to understand why he bruised easilyand why he required more Band-Aidswhen he got a cut. But he’s always been ableeder for years. Why is this diagnosisjust happening now? I didn’t know at thetime, but this reflection is but one of manythat will spark countless yet meaningless“what-ifs” over the course of the nextthree years.

Since the diagnosis, blood tests, Procritinjections and blood transfusions becomemore frequent. Doctors, specialists,hematologists and other white coat cloakedoncologists assimilated themselves into hislife and became fixtures of his weeklyroutine. Terms like dysplasia, acutemyeloid leukemia and increasing blastswere integrated into our everydayvernacular.

In March 2015 his co-workers becameconcerned with his behavior at work.Normally talkative and social, my dad waswithdrawn and unusually quiet. They saidit was warm but he wore his parka all dayin the office. He couldn’t think straight andhis speech became incomprehensible. Theybrought him to the emergency room wheredoctors identified his behavior was due toseverely low hemoglobin and thrombo-cytopenia. This incident jumpstarted anoutpatient chemotherapy programrecommended by his hematologist wherehe would be administered Decitabineintravenously for five days out of everymonth. The treatment was going toincrease and stabilize his blood cell count.When I asked him how his treatments weregoing, how he felt sitting in the roomalongside other patients receivingchemotherapy, he used to deflect fromtalking about his personal experience andinstead tell me about the books he wasreading and what he learned from themduring treatment. He wasn’t beingdismissive — he just didn’t want us toworry.

MDS became either the intenselydiscussed or the eluded topic ofconversation for my family. When wewould talk about MDS, we would typicallyshare what each of us had learned about thecondition online, from friends, or in mysister’s case, through the advice of themedically adept network of her colleaguesat her medical center. Five to ten yearssurvival after diagnosis. There is nospecific cause. I’m not a candidate for bonemarrow transplant. These were commonexpressions in our conversations. My dadwas just being factual. After all, I have


MDS became either the

intensely discussed or the

eluded topic of

conversation for my

family. When we would

talk about MDS, we would

typically share what each

of us had learned about

the condition...

never seen him angry or discouraged. Onlyupset when the Buckeyes let him down inchampionship games or disappointed whenI brought home less than stellar reportcards. Regardless, we stayed positive.Sometimes his blood test results yieldedimprovement. Sometimes they didn’t. Butit wasn’t getting worse. And that’s all wecould hope for.

Almost exactly a year after beingadmitted to the emergency room by hiscolleagues, I received a startling phone callfrom my mom. My dad was being rushedto the hospital in an ambulance because hefell and hit his head but he doesn’tremember how. He called her while shewas at work and told her to come homebecause he was bleeding profusely. Shefound him lying on their bed, with blood-soaked sheets, in the midst of a settingresembling an atrocious crime scene—thecarpet doused with pools of red, bloodyprints stained the walls and closet doors.MDS patients may not produce enoughmature platelets that form blood clots tostop bleeding. He continued to bleed fromthe gash on his head for over 24 hours.

Now our vocabulary expanded to termslike acute subdural hematoma, spleniclaceration and intracerebral hemorrhage.He remained in the hospital for nine days.In those nine days my dad went throughwhat seemed like a never-ending barrage oftests, assessments and therapies from abrand new pantheon of surgeons,oncologists, and intensivists. Throughoutevery exam, no matter how invasive orinconvenient, my dad obliged with utmostgentility and never complained of any painor discomfort.

He was able to return home and by then,he had lost a significant amount of weight.His muscles had severely atrophied and hecouldn’t stay awake for more than threehours without a nap. He couldn’t eat morethan half of his usual portion size andcouldn’t walk without a cane. Cue thethoughts of saying goodbye in a hospice bed.

Days went by with little improvement inhis physical condition. It was hard toaccept how frail he had become. It wasdifficult to look at him without my eyestearing up. But his cheery nature, hispositive spirit, made it impossible to be sadaround him.

The morning of May 7, 2016, threeweeks after my dad was released from thehospital, he passed away. My mom foundhim unconscious on the floor of their livingroom. He stayed up the night beforewatching TV but never made it to bed.Emergency responders were unable toresuscitate him. I remember my mom’shysterical cries on the phone and knew thenthat was the day. No hospice bed. No calmsmile. No one last goodbye.

In the days following his death, I foundmyself routinely explaining what MDS isto friends and family. I became quitecapable of reciting definitions of MDS, andtransforming what were sometimesawkward encounters with sympathizersinto brief informational sessions on thecondition. MDS is a genre of blood

cancers. MDS is a condition in which thepatient’s bone marrow does not producesufficient amounts of healthy blood cells.That’s what MDS is.

It wasn’t until after my dad passedaway I began to think about what MDSwas to him. A struggle that was present forthe greater part of his life, an invisibleenemy he showed up to fight every day.As soft-spoken and unassuming as he was,he was not a victim. He had MDS but hedid not let it define him. Despite thephysical complications and distress heendured because of MDS, he still foundmeans to accomplish everything hewanted to in his lifetime, earn advanceddegrees in science and business andreceive numerous accolades. Despite theanxiety MDS brought him, he providedwell enough for his family so we wereable to grow up in an affluent area andcelebrate our own achievements. He didthis all on his own, never seekingrecognition or praise. A man, who regard-less of his achievements, successes andrespected character, remained inconceivablyhumble. He truly transcends physicalHerculean strength.

This story may not have the happiestending. Or a resolution. But it has a hero.And with this story, I hope others who areaffected by MDS are able to find thestrength to carry on and live their lives asbest they can. Just like my hero did.

As soft-spoken and

unassuming as he was,

he was not a victim.

He had MDS but he did

not let it define him.


45

46

What a Trip!Shirley BullochMidlothian, Virginia

Survivor! Advocate! Fighter! Determined!Researcher! Positive! These words describeme after my 16 year battle to survive MDS.I recorded everything in a journal and calledit “Myelodysplasia – My Journey: Letters toa Friend”. If I had started the journal today,it would be entitled, “Myelodysplasia –What a Trip”.

I was referred to a hematologist in lateMay of 2000 to determine the cause of myextreme fatigue and dizziness. I had beentreated with B12 injections for years foranemia, but the lab results indicated aproblem with my hemoglobin. On June 1,2000, Dr. Yogesh Gandhi performed a bonemarrow biopsy. One week later, he calledto inform me that I had myelodysplasticsyndromes refractory anemia with ringedsideroblasts and megakaryocytes. This wasthe beginning of my trip. I asked him if Ishould cry, and he told me “No”.

I have shed only a few tears, and I becamevery determined to fight and conquer thisdreaded blood disease. I went home and “putmy house in order”, making plans for thefuture. Through my reading, I found that theprognosis was two to five years. I knew that Istill had a lot to accomplish in life and thetime would be much longer. I had justretired in 1999 as an educator at the age of59, and we had completed a month long roadtrip to California. I was not going to spendmy retirement getting ready to die, but toenjoy life.

my home. 16 centers in the US wereconducting the Phase II trials. On June 11,2002, I had my first appointment with Dr.John McCarty. The steps to be part of theclinical trial were in motion – insuranceapproval, finding a sibling donor match,and having batteries of tests. My older sisterwas a match and I started the painful 5-azacitidine injections, three shots a day forseven days with three weeks off, and then arepeat of the cycle until I had completedfour cycles. There were some delays whilemy white cells took their time in generatingmore cells. I spent one week in the hospitalwith pneumonia. Wow! I was the first in thenation with MDS to complete the Phase IItrial with a pre-treatment of 5-azacitidine.On March 10, 2003, I was admitted to thebone marrow transplant wing, my newhome until April 10, 2003. The second dayof stem cell infusion was completed onMarch 15, 2003. To track the progress ofthe longest surviving MDS patient in thatclinical trial, I have easy access by justlooking in the mirror.

When you look at the big picture, it iseasier to fight through each day with thenausea, weakness, and delays. It is easier tofind some humor in each day as it is betterto continue to laugh. I even put on makeupevery morning and put rollers in my hair.Eating was the most difficult as was theneed to continue the Desferal® pump, aniron chelation machine, used for getting ridof the iron overload caused by all thetransfusions. As soon as my hemoglobincounts increased post transplant, it was nolonger necessary to use the pump. Onceduring photopheresis, they removed a pintof blood and that reduced the iron level. Ihad one other phlebotomy, a self-performed one. I had hooked my port to amedication IV at home and must not havehad it tightened correctly as I woke up in apool of blood. My levels were checked thefollowing day, and I apparently removed apint of blood. The benefit was no morephlebotomies for iron overload. Now Ihave to laugh about that experience - I wasonly upset about ruining the comforter onmy bed!

FAMILY STORIESOUR PATIENT STORIES

PATIENT STORIES

Be the Match Run/Walk 2012

At that time, I was considered too oldfor a transplant and would need to survivewith transfusions and experimentaltreatments. My hematologist said thattogether, we would find a new method oftreatment. While I continued to researcheverything, I received 2 units of packed redblood cells every 13 weeks graduallyrequiring the transfusions every 14 to 18days. In May 2001, I had a portacath placedin my upper right chest to make thetransfusions easier. This was the first ofmany portacaths between 2001 and 2012.The hematologist tried lenalidomide,amifostine, and Procrit®. I had adversereactions to the lenalidomide and theamifostine. The Procrit® did not increasemy red blood cell counts as my kidneyswere producing sufficient erythropoietin(EPO). I was given medication to decreasethe number of platelets and the MDS didnot affect my white cell counts. None ofthese drugs provided me with any benefit.

I just knew that there would be positiveoutcomes in my future. In May of 2002while surfing the net, I read the notes fromthe April 2002 Oncology Conference inOrlando, Florida about a clinical trial with amini-peripheral stem cell transplantfollowing four cycles of the experimentaldrug 5-azacitidine (now Vidaza®). One ofthe trials was conducted at VirginiaCommonwealth University (formerlycalled Medical College of Virginia)Hospital in Richmond, just 25 miles fromShirley, Charlotte (donor), Patti, (supporter)

47

Once the transplant was completed, thebattles still continued with theconsequences of the chemotherapy,radiation and the medications. Thetreatments included frequent bone marrowbiopsies, liver biopsy for high liverenzymes (determined cause was one of themedications), photopheresis for skin graftvs. host disease (GVHD), breathingtreatment with pentamidine as I was allergicto the bactrim. There were some downsidesto the transplant. The chemo was low dose,so my plan for my hair to fall out and growin curly didn’t happen as my hair did not fallout. I had to eliminate one of my threefavorites, chocolate. I always said I survivedtransfusions by eating peanut butter, specialdark chocolate and colby jack cheese. I hadto wear a mask when I took part in myfavorite activity: shopping.

There were problems especially with thecatheter for drawing blood. With one ofthem, I had to be in an infusion chair tippedall the way back with my feet in the air, in acontorted position, to get any blood.Eventually that had to be replaced. Betweenthe release date and 2012, there wereadditional hospital stays. A few of the times,the doctors appeared grim. Not me thoughas I never thought about anything butsurvival. One hospital stay was a result of areaction to prednisone which gave me drug-induced diabetes and took away my upperleg muscles. I had to use my arms to lift my

legs in and out of bed. When taken off of theprednisone, the glucose levels returned tonormal, but I had weeks of physical therapyin the hospital and at home to get me out ofthe wheelchair and walking. Until therapywas completed, I lived in the family room,used the lower level bedroom, and could notget up the three steps into the kitchen. Somuch for being independent! I had hospitalstays for congestive heart failure and forlung GVHD. I had skin, mouth, and eyeGVHD. I had photopheresis treatment forseveral years 2004–2009 to resolve the skinGVHD problems and special rinses for themouth irritations. Photopheresis is theprocess of removing blood in cycles,separating the returning red cellsimmediately to the body, and then treatingthe white cells with ultraviolet A light andinfused into the blood stream. I still cannottolerate pepper or citrus. The eye GVHD ledto three different surgeries on the lowereyelids. In 2007, I had a pacemakerimplanted to regulate a slow heartbeat thathad surfaced in 2001. As the result of thechemotherapy and radiation, mouth GVHDand the dry mouth syndrome, I have hadmajor dental surgery. Also as a result of allof this, my kidneys have failed and I havebeen on peritoneal dialysis for two years. Iconquered the cancer and the GVHD. I amsuccessfully dealing with the dialysis. Irefuse to let anything slow me down as Iremain positive and find some humor in myexperiences.


I have laughed, enjoyed life, and wetraveled from 2005–2011 in the motorhome for weeks at a time because I couldcarry my sanitary lodging with me andprepare our own meals. We were able totravel to my sister’s home in Arizona, toPennsylvania Amish Country, MyrtleBeach, New Orleans, our home state ofMichigan, and visits to our daughters inNorth Carolina and Georgia. We wentgemming in North Carolina and Georgia.I developed a hobby of crafting clayjewelry and everyone I know has at leastone piece of my jewelry. I have taken partin the Be the Match Run/Walk. Sincethe transplant in 2003, I have had anadditional 13 years of marriage, two moregrandsons, and I hope through my website(http://shirley.bulloch.org) that I havehelped at least one person as 18,569 peoplehave visited my site.

I have made “Shirley’s Shawls of Hope”for in-hospital transplant patients, and inMay performed Random Acts of Kindnessin memory of my grandson who lost hisbattle against cancer on Mother’s Day2009, at the age of 13. Matthew was a bigpart of my life as we were both diagnosedin 2000, and through the following 9 years,we both traveled the road together. Therewas a special bond between us. We bothhad cancer – with mine being MDS and hisa brain tumor. I continue my fight for bothof us. I have one more goal. At the end ofthis summer, with the help of the MDSFoundation, I plan to help organize asupport group in our area for post-transplant patients. I feel the need to do thisas I have younger transplant friends thatwould benefit from sharing with others.

There have been many bumps in theroad, even some roadblocks, but I haveconquered them with my increasedknowledge and determination. I am proud tobe 76 years old and still maintain a positiveattitude. By the way, September 26, 2012was a memorable day. After manyportacaths, I was finally deported. I amtransfusion free and the only drug I am stilltaking related to the transplant is a dailySingulair as it apparently keeps the lung

Photopheresis Treatment

2009: Matthew and Grandma

48

GVHD as non-symptomatic. I now have adialysis port and do the dialysis at homewhile I sleep. I plan to still be here foranother ten years doing what I lovebest…living.

If I had known the side effects of thetransplant in 2003, my decision to have thetransplant would have been the same. I wasdetermined to beat cancer, not have it beatme. My nurses, doctors and people thatknow me well call me Dr. Shirley. My nursecalls me tenacious. I am just stubborn anddetermined. I must be part of the teaminvolved in my care. The last 16 years havetested me as a person and in many waysmade me stronger. Yes, there has been a lot

of humor in this. I had the support of myhusband, my family, my friends and themany doctors and nurses at North Hospitalin the VCU-MCV Bone Marrow Clinic(Drs. John McCarty, Harold Chung, andToor, Nurses Judy, Laura, and Carol andcountless others) as well as the doctors andnurses in Photopheresis. It has been difficultto condense 16 years into a couple of pages.If you have any questions, please visit mywebsite http://shirley.bulloch.org/ and sendme an email. Bless each of you and keepfighting.

2016—16 years since my MDSdiagnosis and 13 years post-transplant. Thetrip continues… 2009: Shirley and Ross, New Orleans

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49

Living With MDS forMore Than 10 YearsGives HopeNiels JensenSlangerup, Denmark

I am one of the lucky ones! For morethan 10 years I have now lived knowing thatI have myelodysplastic syndromes (MDS).It has been a journey with some bumpsalong the road, some periods of anxiety, andmany periods of joy. So how did it all start?

When Running for a Train or BusWas Not an Option

Getting exhausted and out of breath forseveral minutes by just running a shortdistance to catch a train or bus on the wayto or from work was the first symptom Inoticed. But that was easy to adapt to — Isimply stopped running to catch a bus ortrain. Instead, I walked slowly, and got onthe next bus or train. With time other thingspopped up such as being unable to have anormal conversation for a few minutesafter taking a set of stairs to the secondfloor. That I also adapted to. In early 2004,it was when my secretary noticed that I wasunable to answer her after climbing thestairs to our office that I finally didsomething. She told me to pay my doctor avisit. I did!

My GP had no idea what was wrong,and sent me to the local regional hospitalabout 10 kilometers from my home inSlangerup. That was the start of a year offrequent hospital visits. I was 55 and thatwas—except for a couple of brokenarms — my first real encounter with ourhealth services. The approach used at theregional hospital was that you talked to adoctor, normally the same one at each visit,and he ordered some test, then you wouldget another appointment with the doctor tohear the results of the tests. If the results didnot indicate what was wrong with you, thenthe doctor would order further tests, andyou would get an appointment to hear theresults of those tests. This went on for somemonths without an answer coming up.

Trying to Find the Straw ThatBroke my Breathing

At the time, I was taking a very lowdosage of phenobarbital — a drugcommonly used to prevent epilepticseizures. In the mid 1970’s, I had 2 grandmal seizures. Initially I was put onDilantin®, but that drug lowered my redblood cell count, and I was switched tophenobarbital. The regional hospital doctorfound out that phenobarbital, which issleep inducing, could sometimes also resultin shortness of breath, which I experiencedafter just minor physical activity. Hence, Iwas sent to a neurologist to see if I couldget off phenobarbital. The EEG showedthat my brainwaves still had the features,which had caused my earlier grand malseizures. Nonetheless, the neurologistrecommended that I got off phenobarbital,since at the time I had not had a seizure formore than 15 years. So I did.

Some months later my shortness ofbreath was still very noticeable, and Ireturned to the regional hospital for a bone

marrow biopsy to see if I had leukemia.Before I had the bone marrow biopsy, oneof the nurses was kind enough to tell methat the procedure was like being kicked bya horse — something I have neverexperienced. However, it did not soundpleasant. I was lucky not to have leukemia.Then my visits to the regional hospitalstopped, and some months went by. Mywife told me that we men have to bereminded about everything and that it wastime for me to see my GP again.

I attempted to phone the GP office onemorning to tell about my breathingproblems. This is only possible between8AM and 9AM. After attempting to getthrough for a whole hour, and not havingany success I went to the clinic, and toldthem. They just told me to try again thenext morning. I was furious when I left theclinic, and started my journey to workusing our good public transit system here inDenmark. As I reached the top of the stairsto my second floor office, my mobilephone started ringing. I was out of breathfrom climbing the stairs, but answeredanyway. It was my GP, and she couldimmediately hear that something waswrong. The next day, I had an appointmentto see her. When I saw her the next day, shesent me to a private heart specialist and shealso planned to schedule an appointmentfor me to see a hematologist at the majorregional hospital. It was getting close toChristmas 2004, and I had planned toconference trips in January — one toOkayama, Japan and one in Bialystok,Poland, so I asked her if she could makethe appointment with the hematologistafter February 1st next year. She said OK.

I had the appointment with the heartspecialist before Christmas, and he told methat my heart was pumping fine, but thatmy red blood cell count was about half ofnormal. I told him that my GP was alreadyattempting to get me an appointment with ahematologist, and I went on to have a niceChristmas with my wife and four childrenand two nice conference trips. It was May2005 before I first saw the hematologist atthe major regional hospital in Hillerød.


50

A Very Special WeddingAnniversary Gift

On my first visit, the hematologist toldme that the other hospital had done a bonemarrow biopsy, but had not ordered achromosome analysis so he could not usethat result. He then told my wife and I to gosit in the waiting room, while he found anurse and a bed, so the bone marrowbiopsy could be performed right there. Thatremark completely changed how I sincehave viewed getting a bone marrowbiopsy: It was just another type of medicaltest, just a bit more complex than taking ablood sample. From that day on, there hasalways been someone with me when I go tosee a hospital doctor. Our next appointmentwith the hematologist was on the morningof our 23rd wedding anniversary — July 8,2005. We took the bus to the hospital, andafter a short wait, we were sitting in thehematologist office. He told me that I hadMDS, and that this was a chronic illness,which I would have to live with the rest ofmy life. He would give me Aranesp®, anEPO-like substance, and Neupogen®, agrowth factor, in order to improve my bloodcounts. My wife also recalls him telling usthe FAB category of my MDS. In thewaiting room, a nurse instructed my wife onhow to give the injections and I got my firstEPO shot. The nurse also gave medicationfor the period until our next appointment inabout two months’ time, and told us that therather expensive medication should be keptin a refrigerator. What a gift to start with onour anniversary celebration!

My wife took the bus back to our homein Slangerup to put the medication in ourrefrigerator, while I, due to my severeshortness of breath, waited in the shoppingcenter Slotsarkaderne for her return. It wasa nice summer day, and we started ourcelebration with a walk up and down thewalking streets of Helsingør. For sometime, we had planned to celebrate ouranniversary with dinner at Jan Hurtigkarlsrestaurant in Ålsgårde on the northernshore island we live on, and a short trainride west of Helsingør. This place — now

closed — was known for serving a verynice gourmet dinner with accompanyingwines, and you started with a before dinnerdrink right on the beach towards Kattegat.We had a very nice and unforgettableanniversary dinner in a restaurantoverlooking the approach to Kronborg andØresund on a beautiful summer day andevening. The question: “What is MDS?”had to wait until the next day.

What is this “MDS”?The very next day, both my Anna and I

spent most of the day in front of our tworelatively new laptops. We searched theinternet for information about MDS andfound the MDS Foundation and theMedifocus site. We looked at the samewebsites, looked at the same survivalcurves, but interpreted the information verydifferently. I looked at a diagram, andthought: Great! After more than 10 years,30% of RARS patients are still alive.However my wife looked at the same dataand thought: Bad! After 3 years, 30% ofRARS patients are dead. We both got themessage that the only cure was a bonemarrow transplant, which the hematologistdid not even mention when informing methat I had MDS.

I also discovered, that in the summer of2005, there was just one FDA approveddrug, and it was neither Aranesp orNeupogen—although these were FDAapproved for aplastic anemia, they were notapproved for use by MDS patients. Whythen did I get them? It turns out that the lawsin Denmark allow doctors at major hospitals

to treat patients with drugs approved for thetreatment of related diseases. Aranesp wasapproved for aplastic anemia.

Based on her expectation for how long Iwould live with my chronic illness, my wifecalled our best friends from the time we livedand worked in Sarnia, Canada. Already inSeptember—just as we took possession ofour used VW Lupo 3L—they arrived at ourhome in Slangerup. We had a couple ofwonderful days with more focus onmemories than a chronic illness. And someexcellent sightseeing in North Zealand.

In October 2005, during my second visitafter diagnosis to the hematologist inHillerød, my blood counts had notimproved, and the hematologist told me thathe could not do more for me, and that hewould recommend that I got transferred tothe Hematological Clinic at Rigshospitaletin Copenhagen.

In New Hands at a VerySpecialized Hospital:Rigshospitalet

My first meeting with Rigshospitalet inNovember 2005 was a very positiveexperience. I was scheduled to talk withmy new hematologist, Dr. Lars Kjeldsen,around 10 AM. He told me that my MDSaccording to the International PrognosticScoring System (IPSS) was considered tobe risk level intermediate-1, because all myblood counts, i.e. red cells, white cells, andplatelets, were low. Then he went on to tellus that they were going to perform anumber of tests on me in order to eliminateother diseases and confirm the results fromthe hospital in Hillerød. I was then given alist of three procedures to be performedthat day, and a time to talk with Dr.Kjeldsen after lunch.

At that first meeting, my dose ofAranesp was almost doubled from 500microgram every three weeks to 300microgram every week. At the same time,the amount of Neupogen was increasedfrom one injection per week to 2 or 3injections per week. This programme wascontinued until the middle of 2007. Theresult was that eventually my red blood cell


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count increased to about 75% of normal atthe end of 2007 and 95% of normal at theend of 2008. During 2008, the dose ofAranesp and Neupogen was reduced untilcompletely stopped towards the end of theyear. During 2009 and 2010, my red bloodcell count dropped to around 75% ofnormal, where it has remained until this day.

It is very nice to think back on thetreatment I was offered back in 2005, andsee that in 2013 an international clinicalstudy was started to confirm theScandinavian findings with this treatment.That is great especially in the light of Italianfindings that many blood transfusions (analternative method to treat MDS) are bad ifyou later need a bone marrow transplant. Itis also great to look at the list of drugswhich have been FDA approved fortreatment of MDS: azacitidine in May2004, lenalidomide in December 2005,decitabine in May 2006, and each yearbrings more new treatment options.

Bumps Along the Journey With MDS

In the initial years living with MDS, Iwas a bit careless. For example, during atrip to a conference in Prague in lateAugust 2006, I was sitting 4 hours next toan open hotel window putting the finishingtouches to my conference presentation.While I was at the conference with a ratherbad cold, Anna enjoyed seeing someUnesco Heritage Sites in the CzechRepublic. As we started our drive backtowards Denmark, I was not feelingespecially well. I was lucky to have such agood co-driver in my wife, and we made itback to Slangerup without a plannedstopover. The next day my GP told me, thatI had pneumonia. This was only my firstencounter with pneumonia. Over the years,I have had two more.

Just one and a half months later, Iencountered another bump. I was going toattend a meeting in Luxembourg, and sincethe doctor had made it clear that flying wasnot a good option at that time, we plannedto drive to Luxembourg. When, after astopover in Hameln, we arrived at our hotel

outside Luxembourg City, I had a bathbefore dinner. While I was having my bath,Anna took one look at my leg, and said wehad to go to a hospital. Anna had learnedhow to recognize the appearance of a bloodclot, and she did not like what she saw onmy leg. We drove to Centre Hospitalier duLuxembourg — thank you GPS. After afairly short wait, I had a consultation withan English speaking doctor, who orderedsome blood test. The test indicated apotential blood clot, and she requested thatI come back the next morning for anultrasound scan. The scan showed there wasa blood clot in my lower left leg, and I wasimmediately put on clexane and told not todrive. My wife drove me to the DuPont sitein Luxembourg, where my meeting aboutthe BP Texas City refinery explosion andfire, was to take place. After the meeting,the drive back to Denmark started withAnna at the wheel, and me lying on theback seat with my leg high. Two days laterwe reached Slangerup, but unfortunately anultrasound scan at the local regionalhospital could not confirm the presence of ablood clot, so they did not put me on bloodthinner. That was a mistake.

I hit the third bump in January 2007. Iwas taking the train from Roskilde throughHamburg and Bruxelles to London toattend a meeting of the EFCE WorkingParty on Loss Prevention in London at theoffices of BP. It was a two day meeting andon the morning of the last day, a majorstorm was developing over England, NorthWest France, Belgium, Holland and

western Germany. As I left the BP offices,the wind was already so strong that twopersons had to manage the building glassdoors, and while waiting for the train toLondon a billboard left its stands andlanded on the track. There were no moretrains from that station that day, andhundreds of people scrambling to findalternative means of getting to London.Eventually, I found a bus to Heathrow andfrom there a bus to central London to catchmy Eurostar train to Bruxelles. However,as I approached the Eurostar terminalstation it was announced that all Eurostarservices had been cancelled until nextmorning due to the storm over the Channelarea. My return to Denmark was delayedby 24 hours, a good part of which I spentattempting to get some rest in the Eurostarterminal area. That was a bit of a challenge,due to the many people there andcustodians wanting to do the normalmorning cleaning.

So with a delay of 24 hours and almostno sleep for 48 hours, Anna picked me upat Roskilde. Sunday, we attended thebaptism of my niece’s first child andMonday I drove to work as usual.However, there was nothing usual aboutthe trip home that evening. After passingthrough the forest between Farum andLynge, I hit a curb between a left turninglane and straight lane in an intersection atNymølle. A real bump. I had passed out. Ican recall the drive through the forest, butnot the approach to the intersection. Thebump actually woke me up, and I stopped


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the car on the other side of the intersection,waited for five to ten minutes, and drovehome. I didn’t say anything about theincident — no car damage and no injury tome or others — at the dinner table.However, that night I could not fall asleep,and finally in the middle of the night I toldAnna what had happened. Then I fell asleep.

The very next morning I phoned my GP,who immediately said I was not to drive acar until further notice. Later that day, Iwas admitted to the local hospital, andsubjected to 24/7 monitoring for heartproblems. During the following days, theyscanned my heart — nothing, theyperformed ultrasound of my legs — bloodclot behind one knee, scanned my lungs —reduced capacity in both lungs. I was in thehospital for 10 days. Result: I was put onwarfarin — permanently! And I could notdrive a car for the next six months.

Another result was that my boss at theDepartment of Chemical Engineering atthe Technical University of Denmarkdeemed that I could no longer beresponsible for teaching a regular chemicalengineering course. Teaching was abouthalf of my job, the other half was beingsafety leader at the department, which hadmore than 200 persons and manyexperimental facilities. This confirmed afeeling, which I had even before mydiagnosis, that my boss wanted to get rid ofme. At the end of 2007, he succeeded partlydue to this bump.

However, some of the biggest bumps Ihave experienced were chills. They haveoccurred twice. It starts with a feeling oftiredness, so I lay down to rest on our couch.Then I start shaking and feeling cold. Thefirst time this happened, I just got someorange juice and slept for a few hours, andthe chills were gone. The second time, Annawas home and she took action by calling themedical emergency number, telling them Ihad MDS and what was happening to me.Five minutes later, we were on our way to anoff-hours consultation at the local hospital.The doctor examined me. She even googledthe home page dkpsg.mds-and-you.info, and

concluded she had to admit me to thehospital in order to find out what waswrong. At that time, I had no fever based onboth her observations and my own feelings.

Ten minutes later, I was lying in a bed inthe admission unit, and a nurse asked if Ihad a fever. I said no. She measured mytemperature, and it was 39.5 Celsius. Weremembered a letter, which Dr. LarsKjeldsen at Rigshospitalet had given to usyears ago, about what to do if mytemperature increased beyond 38.5Celsius. Based on this letter, the localhospital contacted Rigshospitalet, and theytold the local hospital to give meintravenous antibiotics twice and thenfollow up with bioclavid. That killed thefever, but to this day I don’t know whatcaused it.

A few days later, I had a previouslyscheduled consultation with Dr. LarsKjeldsen, and I told him about the event.He then told me and my wife, that one candie from these chills, and if it happensagain, then call Rigshospitalet directly.Don’t waste time with the medicalemergency number.

Bumps Keep Coming on thisJourney with MDS

In the fall of 2015, my wife noticed thatmy right eye was closing more and more.At the same time, I noticed that my night

vision on the right was deteriorating, and inretrospect I should have gone to see an eyedoctor. However, as other men I waited —until I had to take my mother, who is 93, tothe eye doctor for a regular checkup. I gotan acute appointment with the eye doctoron April 25th. Within two weeks I got anappointment at the eye clinic at the mainhospital in Copenhagen. On May 11th Iwent there for a preliminary check-up, andafter a 45 minute very careful check-up theeye doctor concluded, that whatever waspressing my right eye forward by about 6millimeter could be related to my MDS.Then I was turned over to the hematolo-gists, who quickly concluded, that in orderto find out more about the thing behind myeye I needed an MRI-scan, so while mywife was enjoying the last day of her walkaround Montenegro, I found myself to be apatient at the MDS Center of Excellence inCopenhagen. Within two hours my headwas subjected to an MRI-scan. Althoughthat procedure does not hurt in anyway, it isvery noisy and after it I felt my balance wasa bit messed up.

Although it was not said directly, it wasquite clear to me that the doctors had asuspicion that my MDS had suddenlymoved along and developed into AML orsomething of that nature. So I had a PET-CT scan to see if things had spread, and atriple bone-marrow biopsy with the


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purpose of getting an update state of thebone-marrow, a sample next-genesequencing and a sample that allowed thedoctors to — if needed — treat me under anew protocol. After the Pentecostholiday — in Denmark, hospitals close forholidays—an eye biopsy was performed.During this appointment, the eye doctorremoved as much material as possible frombehind my eye. The risk here was that onecould damage the main vision nerveconnecting the eye with the brain, i.e., Icould lose my sight in the right eye.Luckily this did not happen, and enoughmaterial was removed to allow my rightperipheral vision to improve.

The initial pathological test on thesample from behind my eye did not showany lymphatic or leukemic development,so I was sent home to wait for the finalanalysis results. Finally on the afternoon ofMay 23rd, exactly four weeks after myinitial examination by a local eye doctor,my hematologist recorded the followingmessage on my answering service: “Niels,I have good news for you!” I phoned herback, and she told me that the pathologistshad found nothing lymphatic or leukemicin the sample from behind my eye. Mywhole family and I could relax again. Mywife and I celebrated the good news with alunch in Tivoli the following day.

During the next four weeks, I think Italked with 4–5 eye doctors and 6–8hematologists. All along, I felt as if therewas a team behind the person relaying anyinformation to me and that gave me a verycomfortable feeling.

The Joys of Living with MDSLiving with MDS is not always a bed of

roses. You regularly have to tell people thatyou walk with to slow down. It can beannoying, but something you easily getused to. The biggest joy are the MDSpatients and professionals I have metinternationally in connection with the MDSLife Beyond Limits campaign, at Celgene’sPartners for Progress events, at NovartisOncology meetings around Europe, and

last but not least the people behind theMDS Foundation. Participation in theseinternational events has brought bothlearning and friendships.

Friendship like that of the late KirbyStone, who after I met him in San Diego inconnection with the MDS Life BeyondLimits Gala Photo Exhibition during theAmerican Society of Hematology (ASH)Annual Congress held in 2011, shared aspreadsheet with his complete MDS-related medical data with me. Or theBelgian gentleman, who I met inEdinburgh and who later created an MDSPatient Support Group in Belgium. Hesaid, “The decision to have a bone marrowtransplant was easy. My doctor told me thatif I did not have transplant then the chancethat he would see me in six months’ timewas less than 5%”. Statistics show that30%–40% of MDS patients who get abone marrow transplant are cured. OrBergit Kühle, whom I also first met in SanDiego, and then some years later in Berlin.She said, “When you get blood it should

depend on how you feel, not on somearbitrary blood count measurement”. Orthe late Robert Weinberg, whom I also metin San Diego, and who lived with MDS formany years without his colleaguesknowing it.

The pictures around this story are alltaken by Ed Kashi during the MDS LifeBeyond Limits photo campaign in the fallof 2011. It was fun to work with him duringone and a half days of shooting photos ofme and my family in and aroundSlangerup. Some of them were exhibited atASH in San Diego, December 2011.

Soon Anna and I can celebrate our 34thanniversary with all of our four children —two boys and two girls — having finishedtheir formal education and going on to newadventures around the world. You alwayshope for the best for your children. And Iam happy to have shared many joyfulmoments with them over the past morethan 10 years of living with MDS,especially during Christmas when theyhave all returned home.

I could go on to mention many moreprofessionals I have met during the last 10years, but I will stop here, and just finishwith the words of the late Kirby Stone:“Living with MDS is about making everysecond count!”

PS: MDS does not consume my wholelife. To mention some non-MDS activities,I am also active with photography and withnew developments in functional modellingto improve plant operations and design.


UPDATE: In our next newsletter, lookfor Niel’s journey in creating MDS DKPatientstøttegruppe. As of the date of thispublication, MDS DK Patientstøttegruppehas joined Lyle Patientforeningen forLymfekræft og Leukæmi. The Danish MDSSupport Group will continue under theumbrella of Lyle and will continue toarrange events directed towards MDSpatients and their relatives. For the timebeing, the Danish language website willcontinue: http://dkpsg.mds-and-you.infoEmail [email protected].

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Living With MDS...Ryan SzantoOcala, Florida

I am 78 years old and have been anMDS patient for 19 years. My desire is toconvey to you my experiences with MDS.I also hope my longevity with MDS willgive you hope and encouragement.

During a routine wellness check, I wasdiagnosed with anemia in July, 1996. I wasa very active, outdoor person and did notfeel there was anything wrong with me, soI did nothing about it. The next year duringanother routine wellness check, the doctorwrote in red pen and circled: significantanemia. He recommended I see myprimary care doctor. I saw her in August1997, and had blood tests run over a fiveweek period. I was told that they did notknow what was wrong with me andrecommended I see a hematologist/oncologist, which I did.

A bone marrow biopsy was performedand it was determined that my anemia wasdue to MDS. I saw this doctor once a weekfor a CBC (blood test) and Procrit® shots.During the next five years and 9 months,Procrit increased gradually from 30,000 to80,000 units to keep my hemoglobin at ahealthy level. In December 2005, I wasswitched from Procrit to bi-weeklyAranesp® injections. This was a blessing.The Aranesp dosage started at 300 mcg for28 injections and now continues at 400mcg. I have had a total of 238 injections asof April 2016.

In June 2001, I had my first bloodtransfusion of 2 units. As of April 2016, Ihave had 473 units of blood. By June 2004,I had iron overload. My ferritin level was2,090. I started iron chelation with a drugcalled Desferal®, which is dispensed withan infusion pump into the stomach 12hours a day, 5 days a week. I continued thistreatment for 18 months.

In the fall of 2005, the MDS Foundationnotified me that there was a new oral drugfor iron overload called Exjade®. It was upfor FDA approval in Washington, DC and I

was asked to testify as to why the drugshould be approved. I was thrilled to go. Itwould be wonderful to get off that pump! Iwent with 14 other patients who also hadiron overload as a result of chronictransfusions for MDS, Sickle Cell Anemia,and Thalassemia. Thankfully, it wasapproved. I started taking Exjade 1500 mgdaily in January 2006. Hurray, this wasanother blessing! Every morning Idissolved the Exjade tablets in water anddrank it.

In July 2015, I was informed of anothernew drug for iron overload called Jadenu®,which is a pill to swallow!!! Even Betterthan Exjade!!! In August, I started on90 mg of Jadenu and I am currently taking360 mg daily.

I took part in a drug trial at MoffittCancer Center in Tampa, Florida forRevlimid® in 2005, but unfortunately it didnot help my MDS. I am not sorry I tookpart in the trial because it might benefitother patients later on by using my bonemarrow for research.

During my first three years, I could notfind any non-MDS specialists who knewanything about the disease. There also wasnot much research on this disease. The firstresearch done was for high-risk MDS. I amclassified as low-risk MDS, RefractoryAnemia with Ringed Sideroblasts (RARS).Much research is now being done for allMDS types.

When I was first diagnosed, I was indenial for about 18 months. My family andI started researching MDS and I startedtalking with my doctor about my options. Irealized my body was the temple of theLord and I had a responsibility to take careof it. That is when my denial shifted to apositive attitude and I accepted mysituation with God’s help. I joined theMDS Foundation and through their Patientand Family Forums, a quarterlypublication, and their website, I havelearned so much about the disease. Doctorsand Nurses attend the Forums and informus of the latest information.

I have done several videos for the drugcompany who makes the iron chelationdrugs I’ve been on. This involvement


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caused me to realize how much I appreciatewhat is taking place to find better ways todeal with iron overload.

I took part in an MDS National Registryfor 5 years that collected data on MDSpatients to determine the differences andsimilarities in patients. What works anddoesn’t work.

Besides learning all that I can andgetting involved, I have used my faith topray for and encourage other patients. I askGod to put in my path anyone He wants meto talk with, pray for, or encourage everyweek when I go to the Oncology Center. Ibelieve this involvement is what is keepingme going. My positive attitude and faithhas been strengthened every day.

My wife and I are family-oriented. Weattend all local family birthday parties,and go to gymnastic practices andcompetitions, T-Ball, baseball, volleyball,and soccer games, cheerleading, andhomecoming events for our grandchildren.We cheer them on to let them know we arethere for them and very proud of them. Wealso have the pleasure of having some ofthe local grandchildren spend the nightwith us. We take them to the skating rink,

bowling, and to the park. I will admit thereare times I do not feel my best, but I pushmyself to go to be a part of their lives.

To summarize, I would say have a goodsupport system whether it be family,friends or church family and learn all thatyou can about MDS. One way is to join theMDS Foundation and go to their website tostay updated on the latest research. Staypositive, be motivated, and get involvedespecially by attending their Patient andCaregiver Forums. Ask questions of yourdoctors and nurses, and most of all, keepGod as your pilot. Yes, it is true I have notbeen physically healed, but God has healedme spiritually and my spirit is what willlive on for eternity.

May God Bless you now and forever.


D O N A T I O N

Stay positive,

be motivated, and get

involved, especially

by attending Patient

and Caregiver Forums.

Hand-MadeMermaid Blanketto Benefit theMDS Foundation

MDS patient Ryan Szanto’s wife,Gloria Szanto, has crocheted thisbeautiful mermaid blanket! She isoffering to auction it off as adonation to the MDS Foundation!

If you are interested inpurchasing this blanket with 100%of the proceeds being donated tothe MDSF, please [email protected]

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� An established university (or equivalent) program� Recognized morphologic expertise in MDS� Available cytogenetics and/or molecular genetics� Ongoing research, including Institutional Review Board–approved clinical trials

To be recognized as a Center of Excellence, an institution must have the following:

UNITED STATESARIZONAMayo Clinic HospitalScottsdale, ArizonaRaoul Tibes, MD, PhDLisa Sproat, MDThe University of Arizona Cancer CenterTucson, ArizonaRavi Krishnadasan, MD, FACPCALIFORNIACedars-Sinai Medical CenterUCLA School of MedicineLos Angeles, CaliforniaH. Phillip Koeffler, MDCity of Hope National Medical CenterDuarte, CaliforniaStephen J. Forman, MDMoores Cancer Center at theUniversity of California, San DiegoRafael Bejar, MD, PhDPeter Curtin, MDStanford University Medical CenterStanford, CaliforniaPeter L. Greenberg, MDUCLA Center for Health SciencesLos Angeles, CaliforniaGary J. Schiller, MDUniversity of Southern CaliforniaKeck School of MedicineLos Angeles, CaliforniaCasey L. O’Connell, MDCOLORADOUniversity of ColoradoSchool of MedicineUniversity of Colorado Cancer CenterAurora, ColoradoDaniel Aaron Pollyea, MD, MS

CONNECTICUTYale Cancer Center/Smilow Cancer HospitalYale Univesity School of MedicineNew Haven, ConnecticutSteven D. Gore, MD

FLORIDAAll Children’s HospitalSt. Petersburg, FloridaGregory Hale, MDMayo ClinicJacksonville, FloridaJames M. Foran, MD

Moffitt Cancer CenterTampa, FloridaAlan F. List, MDSylvester Comprehensive Cancer CenterUniversity of Miami Miller School of MedicineMiami, FloridaStephen D. Nimer, MDUniversity of Florida Shands HospitalGainesville, FloridaChristopher R. Cogle, MD

GEORGIAEmory Winship Cancer InstituteEmory University School of MedicineAtlanta, GeorgiaAmelia Langston, MDThe Blood and Marrow Transplant Program at Northside HospitalAtlanta, GeorgiaAsad Bashey, MDILLINOISLoyola University ChicagoCardinal Bernardin Cancer CenterMaywood, IllinoisScott E. Smith, MD, PhDRobert H. Lurie Comprehensive CancerCenter of Northwestern UniversityFeinberg School of MedicineChicago, IllinoisOlga Frankfurt, MDRush University Medical CenterChicago, IllinoisJamile Shammo, MDUniversity of Chicago Medical CenterChicago, IllinoisRichard A. Larson, MD

INDIANAIndiana UniversitySimon Cancer CenterIndianapolis, IndianaLarry Cripe, MD/Hamid Sayar, MD, MS

IOWAThe University of Iowa Hospitals and Clinics, Holden Cancer CenterIowa City, IowaCarlos E. Vigil-Gonzales, MD

MARYLANDJohns Hopkins University School of MedicineBaltimore, MarylandAmy Elizabeth DeZern, MD

University of MarylandGreenebaum Cancer CenterBaltimore, MarylandMaria R. Baer, MDMASSACHUSETTSDana-Farber Cancer InstituteBoston, MassachusettsRichard M. Stone, MD/David P.Steensma, MD/Benjamin Ebert, MD, PhDMassachusetts General HospitalCancer CenterBoston, MassachusettsTimothy Graubert, MDTufts University School of MedicineTufts Medical CenterBoston, MassachusettsKellie Sprague, MD

MICHIGANBarbara Ann Karmanos CancerInstitute, Wayne State UniversityDetroit, Michigan Charles A. Schiffer, MDWilliam Beaumont HospitalCancer CenterRoyal Oak, MichiganIshmael Jaiyesimi, DOMINNESOTAMayo ClinicRochester, MinnesotaMark R. Litzow, MDUniversity of Minnesota Medical Center, Fairview Universityof Minnesota Medical SchoolMinneapolis, Minnesota Erica D. Warlick, MDMISSOURIWashington University School of MedicineSiteman Cancer CenterSt. Louis, MissouriJohn F. DiPersio, MD, PhDNEBRASKAUniversity of Nebraska Medical CenterOmaha, NebraskaLori Maness, MDNEW HAMPSHIREDartmouth-Hitchcock MedicalCenter and Norris Cotton Cancer CenterLebanon, New HampshireKenneth R. Meehan, MD

� Documentation of peer-reviewedpublications in the field

Please contact the Foundation for further information and an application form for your center.The following centers have qualified as MDS Centers of Excellence:

NEW JERSEYThe Cancer Center of Hackensack University Medical CenterHackensack, New JerseyStuart Goldberg, MD

NEW YORKAlbert Einstein Cancer Center/Albert EinsteinCollege of Medicine of Yeshiva UniversityBronx, New YorkAmit Verma, MDColumbia University Medical CenterNew York, New YorkAzra Raza, MDMemorial Sloan-Kettering Cancer CenterNew York, New YorkVirginia M. Klimek, MDMonter Cancer Center/NSLIJ Cancer InstituteLake Success, New YorkSteven L. Allen, MDIcahn School of Medicine at Mount SinaiNew York, New YorkLewis R. Silverman, MDNew York Medical College/Westchester Medical CenterZalmen A. Arlin Cancer CenterValhalla, New YorkKaren Seiter, MDRoswell Park Cancer CenterBuffalo, New YorkElizabeth Griffiths, MD/James E. Thompson, MDUniversity of Rochester Medical CenterRochester, New YorkJane L. Liesveld, MDWeill Medical College of Cornell UniversityNew York Presbyterian HospitalNew York, New YorkGail J. Roboz, MD

NORTH CAROLINADuke University Medical CenterDurham, North CarolinaCarlos M. deCastro, MDWake Forest University School of MedicineComprehensive Cancer CenterWinston-Salem, North CarolinaBayard L. Powell, MD

OHIOCleveland Clinic Foundation Taussig Cancer CenterCleveland, OhioJaroslaw Maciejewski, MD, PhDMikkael Sekeres, MD, MS

MDS CENTERS OF EXCELLENCEWould you like your treatment center to become part of the referral system for MDS patients and be designated as a Center of Excellence?

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The Ohio State ComprehensiveCancer Center, James Cancer Hospital and Solove Research InstituteColumbus, OhioAlison R. Walker, MDPENNSYLVANIAAllegheny Health Network Cancer InstituteWestern Pennsylvania HospitalPittsburgh, PennsylvaniaSalman Fazal, MDFox Chase Cancer CenterPhiladelphia, PennsylvaniaPatricia Kropf, MDUniversity of Pennsylvania Cancer CenterPhiladelphia, PennsylvaniaSelina Luger, MDUPMC Cancer CenterPittsburgh, PennsylvaniaAnastasios Raptis, MD/James M. Rossetti, DO

TENNESSEEVanderbilt University Medical CenterNashville, TennesseeSanjay Mohan, MD/Michael R. Savona, MD

TEXASCancer Care Centers of South TexasSan Antonio, TexasRoger Lyons, MDTexas Oncology, MidtownAustin, TexasRichard Helmer, III, MDUniversity of TexasMD Anderson Cancer CenterHouston, TexasGuillermo Garcia-Manero, MD/Hagop Kantarjian, MDUniversity of TexasSouthwestern Medical CenterDallas, TexasRobert H. Collins, Jr., MD, FACPWASHINGTONFred Hutchinson Cancer Research CenterUniversity of WashingtonSeattle Cancer Care AllianceSeattle, WashingtonJoachim Deeg, MD/Elihu Estey, MDWASHINGTON, DCGeorgetown University HospitalLombardi Comprehensive Cancer CenterWashington, D.C.Catherine Broome, MDGeorge Washington UniversityVA Medical CenterWashington, D.C.Charles S. Hesdorffer, MDWISCONSINAmerican Family Children’s HospitalUniversity of Wisconsin HealthMadison, WisconsinInga Hofmann, MDMedical College of WisconsinBone Marrow Transplant ProgramMilwaukee, WisconsinParameswaran Hari, MDUniversity of WisconsinMadison Medical SchoolMadison, WisconsinMark B. Juckett, MD

Toronto SunnybrookRegional Cancer CentreToronto, Ontario, CanadaRichard A. Wells, MDUniversity of TorontoHospital for Sick ChildrenToronto, Ontario, CanadaYigal Dror, MD

CHINAGuangdong General Hospital &Guangdong Academy of Medical Sciences Guangzhou, ChinaXin Du, MD, PhDInstitute of Hematology and Blood Diseases HospitalChinese Academy of Medical SciencesTianjin, ChinaZhijian Xiao, MDThe First Affiliated Hospital of Soochow University Jiangsu Institute of HematologyJiangsu Province, ChinaSuning Chen, MD, PhDThe Sixth Hospital Affliated toShanghai Jiaotong UniversityShanghai, ChinaXiao Li, MD, PhD

CZECH REPUBLICInstitute of Hematology& Blood TransfusionPrague, Czech RepublicJaroslav Cermák, MD, PhD

DENMARKOdense University HospitalThe University of Southern DenmarkOdense, DenmarkGitte Birk Kerndrup, MDRigshospitalet National University HospitalCopenhagen, DenmarkKirsten Grønbaek, MDLars Kjeldsen, MD, PhD

FRANCECentre Henri BecquerelRouen University School of MedicineRouen, FranceAspasia Stamatoullas, MDCentre Hospitalier Universitaire (CHU) de Angers Service des Maladies du SangAngers, FranceNorbert Ifrah, MDCentre Hospitalier Universitaire(CHU) de GrenobleGrenoble, FranceJean-Yves Cahn, MDCentre Hospitalier Universitaire (CHU) de Limoges Hôpital DupuytrenLimoges, FranceDominique Bordessoule, MDCentre Hospitalier Universitaire (CHU) de NancyNancy, FranceAgnés Guerci-Bresler, MD, PhD

Centre Hospitalier Universitaire (CHU) de Tours – BretonneauTours, FranceEmmanuel Gyan, MD, PhDHôpital Avicenne/University Paris XIIIBobigny, FranceCharikleia Kelaidi, MDHôpital Cochin/University Paris VParis, FranceFrancois Dreyfus, MDHôpital Saint Louis/University Paris VIIParis, FrancePierre Fenaux, MD, PhDChristine Chomienne, MD, PhDHôpital Saint-Vincent de Paul (Lille)Lille, FranceChristian Rose, MDInstitut Paoli-CalmettesMarseille, FranceNorbert Vey, MDService des Maladies du SangHôpital Claude HuriezLille, FranceBruno Quesnel, MD

GERMANYGeorg-August-Universität GöttingenGöttingen, GermanyDetlef Haase, MD, PhDHannover Medical SchoolMedizinische Hochschule HannoverHannover, GermanyArnold Ganser, MDHeinrich-Heine Universität DüsseldorfUniversity HospitalDüsseldorf, GermanyUlrich Germing, MDJohann Wolfgang Goethe UniversitätFrankfurt Main, GermanyGesine Bug, MDKlinikum Rechts der IsarTechnical University of MunichMunich, GermanyKatharina Götze, MDMLL Münchner Leukämielabor Munich, GermanyTorsten Haferlach, MDRems-Murr-Klinik WinnendenWinnenden, GermanyStefani Parmentier, MDSt. Johannes HospitalHeinrich-Heine Universität Duisburg, GermanyCarlo Aul, MD, PhDAristotle Giagounidis, MD, PhDUniversity of Heidelberg Medical Center St. Lukas Klinik SolingenSolingen, GermanyUlrich Mahlknecht, MD, PhD

OUTSIDE THE UNITED STATES

ARGENTINASanatorio Sagrado del CorazónBuenos Aires, ArgentinaMarcelo Iastrebner, MD

ARMENIAMuratsan University HospitalComplex of Yerevan State Medical UniversityYerevan, ArmeniaGevorg Tamamyan, MD

AUSTRALIAPeter MacCallum Cancer InstituteUniversity of MelbourneEast Melbourne, AustraliaJohn F. Seymour, MDThe Royal Melbourne HospitalParkville Victoria, AustraliaDavid Ritchie, MDUniversity of TasmaniaRoyal Hobart HospitalHobart, Tasmania, Australia

AUSTRIAHanusch HospitalMedical University of ViennaVienna, AustriaMichael Pfeilstöcker, MDMedical University of ViennaVienna, AustriaPeter Valent, MDUniversity Hospital of InnsbruckInnsbruck, AustriaReinhard Stauder, MD

BELGIUMAZ Sint-Jan AVBrugge, BelgiumDominik Selleslag, MDUniversity Hospital LeuvenLeuven, BelgiumMarielle Beckers, MD, PhDMichel Delforge, MD, PhD

BRAZILAC Camargo Hospital –Cancer CenterSão Paulo, BrazilLuiz Fernando Lopes, MD, PhDHospital das clínicas da Faculdade de Medicina da Universidade de São PauloSão Paulo, Brazil Elvira D. Rodrigues Pereira Velloso, MD, PhDUniversidade Federal de CearáCeará, BrazilSilvia Maria M. Magalhães, MD, PhDUniversidade Federal de São PauloSão Paulo, BrazilMaria de Lourdes Chauffaille, MD, PhD

CANADAPrincess Margaret HospitalToronto, Ontario, CanadaKaren Yee, MD

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Albert-Ludwigs-UniversitätFreiburgFreiburg, GermanyMichael Lübbert, MD, PhDUniversität HamburgHamburg, GermanyNicolaus Kröger, MD, PhDUniversitätsklinikum Carl Gustav CarusDresden, GermanyUwe Platzbecker, MDUniversity Children’s HospitalFreiburg, GermanyCharlotte Niemeyer, MDUniversity of CologneCologne, GermanyKarl-Anton Kreuzer, MDUniversity Hospital MannheimMannheim, GermanyWolf-Karsten Hofmann, MD

GREECEPatras University HospitalPatras, GreeceArgiris Symeonidis, MDUniversity of Athens Laikon HospitalAthens, GreeceNora Viniou, MDUniversity General Hospital AttikonAthens, GreeceVassiliki Pappa, MD

HUNGARYSemmelweis University School of MedicineBudapest, HungaryJudit Várkonyi, MD, PhD

INDIATata Medical Centre Kolkata, IndiaCol (Dr.) Deepak Kumar Mishra, MDTata Memorial HospitalMumbai, IndiaPurvish Parikh, MD

IRELANDAdelaide and Meath HospitalDublin, IrelandHelen Enright, MD

ISRAELTel-Aviv Sourasky Medical CenterTel-Aviv, IsraelMoshe Mittelman, MDChaim Sheba Medical CenterTel Hashomer, IsraelDrorit Grizim Merkel, MD

ITALYCancer Center – IRCCSHumanitas Research HospitalMilan, ItalyMatteo G. Della Porta, MD

Centro di RiferimentoOncologico di Basilicata (CROB)Rionero in Vulture (PZ), ItalyPellegrino Musto, MD Istituto di EmatologiaUniversita’ Cattolica Sacro CuoreRome, ItalyGiuseppe Leone, MDPoliclinico Tor VergataRome, ItalySergio Amadori, MDMaria Teresa Voso, MDS. Eugenio HospitalTor Vergata UniversityRome, ItalyPaolo de Fabritiis, MDPasquale Niscola, MDUniversity of FlorenceAzienda OSP CareggiFlorence, ItalyValeria Santini, MDUniversity of Pavia School of Medicine Fondazione IRCCS Policlinico San MatteoPavia, ItalyMario Cazzola, MD

JAPANKyoto University HospitalKyoto, JapanAkifumi Takaori, MDMetropolitan Research Center for Blood DisordersShin-Yurigaoka General HospitalKanagawa, JapanKiyoyuki Ogata, MD, FACPNagasaki University HospitalSchool of MedicineAtomic Bomb Disease InstituteNagasaki City, JapanYasushi Miyazaki, MDSaitama International Medical CenterSaitama Medical UniversityHidaka, Saitama, JapanAkira Matsuda, MDTokyo Medical CollegeTokyo, JapanKazuma Ohyashiki, MD, PhD

KOREACatholic Blood and Marrow Transplantation CenterThe Catholic University of KoreaSeoul, KoreaYoo-Jin Kim, MDSeoul National University HospitalSeoul National University College of MedicineSeoul, KoreaDong Soon Lee, MD, PhDYonsei Cancer Cetnre, Severance HospitalYonsei University College of MedicineSeoul, KoreaJune-Won Cheong, MD, PhD

THE NETHERLANDSRadboud University Nijmegen Medical CenterNijmegen, The NetherlandsSaskia M.C. Langemeijer, MDVrije Universiteit Medical CenterAmsterdam, The NetherlandsArjan A. van de Loosdrecht, MD, PhD

POLANDJagiellonian University Collegium MedicumKraków, PolandAleksander Skotnicki, MD, PhD

PORTUGALHospital de Santa MariaLisbon, PortugalJoao F. Lacerda, MD

SAUDI ARABIAKing Faisal Specialist Hospital & Research CentreRiyadh, Saudi ArabiaAmr Hanbali, MDKing Khaled University HospitalKing Saud UniversityRiyadh, Saudi ArabiaAk Almomen, MD

SINGAPORESingapore General HospitalSingaporeAloysius Ho, MD

SOUTH AFRICAUniversity of Cape TownGroote Schuur HospitalCape Town, South AfricaNicolas Novitzky, MD, PhD

SPAINHospital Universitario de SalamancaSalamanca, SpainConsuelo del Cañizo, MD, PhDHospital Universitario La FeValencia, SpainMiguel A. Sanz, MD, PhDHospital Universitario Vall d’HebronLaboratorio del Citologia-CitogéneticaBarcelona, SpainMaria Teresa Vallespi-Sole, MD, PhD

SWEDENKarolinska Institute atKarolinska University Hospital HuddingeStockholm, SwedenEva Hellström-Lindberg, MD, PhD

SWITZERLANDBasel University HospitalBasel, SwitzerlandJakob R. Passweg, MD, MSBern University Hospital and University of BernBern, SwitzerlandNicolas Bonadies, MD

University Hospital ZurichZurich, SwitzerlandMarkus G. Manz, MDStefan Balabanov, MD

TAIWANChang Gung Memorial HospitalChang Gung UniversityTaoyuan, TaiwanLee-Yung Shih, MDNational Taiwan University HospitalTaipei, TaiwanHwei-Fang Tien, MD, PhD

THAILANDKing Chulalongkorn Memorial HospitalPathumwan, Bangkok, ThailandTanin Intragumtornchai, MD

TUNISIAHospital Aziza OthmanaTunis, TunisiaBalkis Meddeb, MD

TURKEYAnkara University School of Medicine HospitalAnkara, TurkeyOsman Ilhan, MD

UKRAINEResearch Center for Radiation MedicineKiev, UkraineDimitry Bazyka, MD

UNITED KINGDOMAberdeen Royal InfirmaryAberdeen University School of MedicineForesterhill, Aberdeen, ScotlandDominic Culligan, MDChristie NHS Foundation TrustManchester, United KingdomMike Dennis, MDKing’s College London &King’s College HospitalLondon, United KingdomGhulam J. Mufti, DM, FRCP, FRCPathQueen Elizabeth HospitalUniversity Hospital Birmingham NHS TrustBirmingham, United KingdomManoj Raghavan, MDRadcliffe Hospitals and University of OxfordOxford, United KingdomParesh Vyas, MD Royal Bournemouth HospitalBournemouth, United KingdomSally Killick, MDSt. James’s University HospitalSt. James’s Institute of OncologyLeeds, United KingdomDavid T. Bowen, MDUniversity Hospital of WalesCardiff, WalesJonathan Kell, MD

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Thinking of joining the MDS Foundation as a Professional Member? Our Professional Members are recognized on our MDS Foundation website as well as in our printed newsletters. Professional members

also enjoy discounted registration rates at our biennial International Symposia, as well as a discounted subscription rate to LeukemiaResearch. In addition, membership fees help to support educational programs, events, research and advocacy efforts.

To join the MDS Foundation and help us fulfill our mission of moving closer to a cure for MDS, please visit our website athttp://www.mds-foundation.org/professional-annual-membership-application.

Camille Abboud, MDSophia Adamia, PhDCalum Adams, ANPAref Al-Kali, MDSteven L. Allen, MD,Hanan Alwazzan, MDErica Andersen, MDMartha Arellano, MDChristopher Arthur, MDAnita Atema, MScMaria R. Baer, MDGabriela Baerlocher, MDHaiyan Bao, MDAsad Bashey, MDMarielle Beckers, MDKatharine Bee, PhDRafael Bejar, MD, PhDMonika Belicková, MDJohn M. Bennett, MDHarriet A. Bering, MDMassimo Bernardi, MDEmmanuel C. Besa, MDNicolas Bonadies, MDDominique Bordessoule, MDDavid T. Bowen, MDRandy A. Brown, MDAndrew M. Brunner, MDRena Buckstein, MD, FRCPCGesine Bug, MDThomas W. Butler, MDHuojun Cao, MDJheremy Enrique Reyes Castellanos, MDHugo Castro-Malaspina, MDJaroslav Čermák, MD, PhDMustafa Cetiner, MDVictor Chang, MD, FACPLynette Chee, MDLimei Chen, MDQiusheng Chen, MD

Suning Chen, MD, PhDJason X. Cheng, MD, PhDJune-Won Cheong, MDLaura Yolanda Chialanza Garcia, MDJonathan K. Cho, MDChristopher R. Cogle, MDRobert H. Collins, Jr., MD, FACPSeth J. Corey, MDRachel Cotter, RNLarry Cripe, MDPeter T. Curtin, MDLucy CussansCarlos M. de Castro, MDFabio Pires De Souza Santos, MDTheo J.M. de Witte, MD, PhDConsuelo del Cañizo, MD, PhDH. Joachim Deeg, MDMichel Delforge, MD, PhDMatteo G. Della Porta, MDMike Dennis, MDAmy E. DeZern, MD, MHSBruce Dezube, MDRishi Dhawan, MDJohn F. DiPersio, MD, PhDMinghui Duan, MDTheofanis Economopoulos, MDM. Tarek Elghetany, MDSarah England, PA-CSalman Fazal, MDLenn Fechter, RN, BSNDonald I. Feinstein, MD, MACPSandor Fekete, MDJosè Maria Ferro, MDMaria E. Figueroa, MDKalman Filanovsky, MDJames M. Foran, MD, FRCPArnold Ganser, MDAlejandro Garcia-Hernandez, MDGuillermo Garcia-Manero, MD

Michelle Geddes, MDAaron T. Gerds, MD, MSUlrich Germing, MDGudrun Goehring, MDStuart L. Goldberg, MDCarlos Vigil Gonzales, MDSteven D. Gore, MDKatharina Götze, MDMarie Pierre Gourin, MDTimothy Graubert, MDPeter L. Greenberg, MDElizabeth A. Griffiths, MDKirsten Grønbaek, MDEmmanuel Gyan, MD, PhDDetlef Haase, MD, PhDTorsten Haferlach, MDStephanie Halene, MDAmr Hanbali, MDCurtis A. Hanson, MDRobert Hast, MDBrenda HawkesGuangsheng He, MDEva Hellström-Lindberg, MD, PhDCharles Hesdorffer, MDAndreas Himmelmann, MDMichel Hoessly, MDInga Hofmann, MD,Gang Huang, PhDClaudio Marcelo Iastrebner, MDIshmael Jaiyesimi, DOBrian A. Jonas, MD, PhDMark Juckett, MDHagop M. Kantarjian, MDSuresh B. Katakkar, MD, FRCPCJonathan Kell, MDPeter Keller, MDMelita Kenealy, MDWolfgang Kern, MDLeslie Kerns, RN

NEW MDSF PROFESSIONAL MEMBERSHIP2014 RARE DISEASE DAYJOIN THE MDS FOUNDATION

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Sally Killick, MDLars Kjeldsen, MD, PhDJeffery Klco, MDVirginia M. Klimek, MDH. Phillip Koeffler, MDRami Komrokji, MDJanusz Krawczyk, MDRavi Krishnadasan, MD, FACPNicolaus Kröger, MD, PhDRajat Kumar, MDYueyun Lai, MDWendy Lam, MDSaskia Langemeijer, MDAmelia Langston, MDRichard A. Larson, MDLaszlo Leb, MDJohanna B. Leonowicz, MDBing Li, MDXiao Li, MD, PhDJane L. Liesveld, MDAlan F. List, MDMark R. Litzow, MDJohannes Loferer, MDSelina Luger, MDRoger M. Lyons, MDUlrich Mahlknecht, MD, PhDGabriel N. Mannis, MDMarkus G. Manz, MDKatherine Marsden, MDYvonne Matienko, LPNAkira Matsuda, MDPhilip L. McCarthy, MDRichard McMasters, MDKenneth R. Meehan, MDRaul R. Mena, MDDrorit Grizim Merkel, MDIsrael Wolfgang Meyer, MDMoshe Mittelman, MDYasushi Miyazaki, MDSanjay Mohan, MDJoseph O. Moore, MDAlvaro Moreno-Aspitia, MDLynn Moscinski, MDGhulam J. Mufti, DM, FRCP, FRCPathSuneel D. Mundle, PhDTracy Murphy, MD

Han Myint, MD, PhDPhuong L. Nguyen, MDCharlotte Niemeyer, MDStephen D. Nimer, MDBenet Nomdedeu, MDNicolas Novitzky, MDNolyn Nyatanga, MDCasey L. O’Connell, MDMargaret O’Donnell, MDKiyoyuki Ogata, MD, FACPSeishi Ogawa, MDKazuma Ohyashiki, MD, PhDHoward S. Oster, MD, PhDRose Ann Padua, PhDVassiliki Pappa, MDStefani Parmentier, MDJakob R. Passweg, MDMichael Petrone, MDMichael Pfeilstöcker, MDUwe Platzbecker, MDVicki Plumb, RNDaniel Pollyea, MD, MSJulio Pose Cabarcos, MDBayard L. Powell, MDGabrielle T. Prince, MDBruno Quesnel, MDFernando Ramos, MD, PhD, MPHAzra Raza, MDShannon Reilly, NPGail Roboz, MDElvira Rodrigues Pereira Velloso MD, PhDInga Mandac Rogulj, MDChristian Rose, MDAlicia Rovo, MDGrazia Sanpaolo, MDMichael R. Savona, MD, FACPHamid Sayar, MD, MSAleksandar Savic, MDMary Lynn Savoie, MDGary J. Schiller, MDJason R. Schwartz, MDKaren Seiter, MDDominik Selleslag, MDJohn F. Seymour, MDRichard K. Shadduck, MDJamile M. Shammo, MD

Lee-Yung Shih, MDLewis R. Silverman, MDScott E. Smith, MD, PhD, FACPQiang Song, MDYuanbin Song, MDEduardo Sotomayor, MDKellie Sprague, MDAspasia Stamatoullas, MDMargarete Stampfl-Mattersberger, MDHarry Staszewski, MDReinhard Stauder, MDDavid P. Steensma, MDGalia Stemer, MDArgiris S. Symeonidis, MDAkifumi Takaori, MDGevorg Tamamyan, MDJames E. Thompson, MDRaoul Tibes, MDHwei-Fiang Tien, MDMasao Tomonaga, MDHongyan Tong, MDZuzana Tothova, MD, PhDArjan van de Loosdrecht, MD, PhDAmit Verma, MDCarolina Villegas Da Ros, MDAthina Nora Viniou, MDAlison R. Walker, MDXiaomin Wang, MDXin Wang, MDZhen Wang, MDRichard A. Wells, MDJohn P. Whitecar, Jr., MDGail Wilmot, RNLeah Wolfe, R.Ph.Anthony Woods, MDDepei Wu, MDZhijian Xiao, MDYumi Yamamoto, BAKaren Yee, MDYataro Yoshida, MDJ. Dudley Youman, MDLinda Young, RNWenjuan Yu, MDLing Zhang, MDNancy Zhu, MD

2014 RARE DISEASE DAYJOIN THE MDS FOUNDATION

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CONTRIBUTIONS TO THE MDS FOUNDATION

Doctor Stuart Goldberg • Nativite Miller• David and Shirley Fenner • Linda Day• Ralph and Salome Hamaker • AbbieC. Carter • Alison Walker • CyndaSolberg • Melissa Kong • Cindy Newell• Virginia Watson • Martina Wiedmayer• Pamela Mroczkowski • BrendaHeymann • Connie Smith • MatthewGonzales • George and Claudette Latsko• Ronald and Carol Solberg • Warrenand Dorothy Hawkins • GeorgeGaluschak • Patricia Seyller • NicholasPeters • Karen Clapp • The Arthur J.Gallagher Foundation • John and CarolBennett • Karen J. Clapp, • Claire-Elizabeth Sloan • Sue Patrick • Ronaldand Helen Vanskiver • Janann Anderson• Julie Harris • Harry Klapper • Kevinand Maudeen Dinan • Steven andMaxine Balaban • Kevin Lawlor • MarlaLondon • Joseph G. Lerario • LindseyBrown • Jennifer McCann • RandallWong • Alice Healy • Joseph and DonnaGill • Ralph S. Blumenstock • Greggand Dona Joly • Lynn Bressman • DanFritz • Jerry W. Pike • Carl and PhyllisStaplin • Thomas B. Snodgrass • SallyHanna • Edwin Rozendal • W.C. Hall •Pat Thompson • Renee Conrad • CynthiaHill • Sharon Stone • Rita Labella •Charles Balstad • Judy Danko • MarcyDart • Leonard McAdams • David Meier

• Joanne Kubiak • Mary Roberts •Leonard Yool • Darryl Hilton • CarolPomeroy • Mary Jane Klements • YvetteVine • Timothy Morris • Marcie Vanderlee• Gerard and Benita Berman • WilliamFrost • Dennis and Shirley Schiffler •Raymond L. Kuehl • Rita Paul • PaulKurtis • James Dowd • Doris Gray •Dorothy M. Hale • John Demkowski •Patricia Milton Koury • Diana McClureRussell • David Hintzke • Nancy Killion• H. Howard Stephenson • James andDebra Phillips • Gus Tulloss • Don andShirley Raines • Thomas Fisher • DebraLauer • Dennis and Randy Belluzzo •Raul and Yolanda Schcolnick • MeredithR. Bruce • Daniel and Andrea Reese •Edward and Linda Kotkiewicz • DeRolfDevelopment • William Boehnen •Mary Bartella • Zita Sulzberger •Richard and Susan Hilser • EleanorTurner • Janet B. Warfield • James andJosephine Diedrich • Pam Whitmore •Rose Staikos • Sarah Whitehead •Konnie Miller • Sally Ferguson •Marguerite Drasler • William andSuzanne Gross • Joan Obrien • LindaMarie • Sanford Donsky • Annie G.Roberts • Carmen Garcia • SusanYnosencio • Jeanette Allen • Helena A.Miley • Virginia Colatruglio • RichardDoughty • Ronald and Mary Herndon •

The MDS Foundation relies on gifts to further its work. We would like to acknowledge the generosity of the following individuals and organizations that have recently provided gifts to the Foundation:

GIFTS TO THE FOUNDATION

THANKYOU...Irving Silverstein • Lori Meyerer • JudeWiggins • Charles H. Welch • Elisa Evans• Jennifer Thrash • Karin Schmeiss •William Haas • Barbara A. Liddell •Jane Springer • Linda Desch • Johnnyand Serafima Glass • Barbara Rynders •JoAnn Scimanico • Frances Applebaum• Ellen Propp • Joan Hayes • VaskenKelerchian • Charles Bicht • Charles B.Vogt • Joe Rash • Renee Conrad •ASMC-Buckeye Chapter • RogerKloepping • Frederic and KathleenLeverenz • Sherri Kincaid • MargaretMorgan • Michael H. O’Neal •Raymond P. Daniels • Ruth Horsfall •Mary K. Miyawaki • Sagar C. Sharma •Joyce Printz • Pam Finer • The Henry &Marilyn Taub Foundation • PeterMariniello • Merritt Blake

THANK YOU TO OUR SPONSORS FOR THEIR SUPPORT

ROBERT JAY WEINBERG MEMORIAL

DonationsHave BeenMade By:RochelleOstroff-WeinbergWynnewood, PA

The MDS Foundation’s Work Helps Keep Memories Alive

Janice L. Allen • Guido J. Arquilla • Palma Azzariti • Neil Baker • Kathleen B. Baniewicz • Rochelle Bank• William J. Bauzan • Jennifer L. Bell • John Bena • Wayne Bender • Barbara Bennett • Juliette G. Bisson• Walter Bitz • Andrea Bonnevie • Lorraine Bordonaro • William J. Bouzan • Joe Boyd • Michael Brecker• Chuck Brune • David Hammond Burke • Francis Stuart Carson • Dolores Cellini • Joseph J. Cerrone •Victor Clementoni • Dorothy Cook • Billy Gene Cooper • Rodger Crager • John George (Jack) Crider• Charles “Chuck” Davis • Alessandro Degl’ Innocenti • Rebecca Lynn Reed Demori • Nancy Dindorf •William Doherty • Irwin Dubin • Donald Elliott, Sr. • Ramon A. Evangelista • James Felty, Sr. • Luis F.Figueroa • Rosemary Fortinash • Nancy C. Fox • Joel Fried • Sam Friedman • Valerie A. Geib • John C.Gessner • Erna Gross • Sven “Gus” Gustafson • Karen Mae Haigh • James Hartl • Gloria Harrida • NancyHarwell • Robert Lee Hayes • George M. Herrmann • Erna Herzog • Chuck Highbaugh • Rita Hisrich •Diane Horwitz • Don Humphrey • Patricia Janevic • Major G. Johnson • Robert R. Johnson • Lee Kaasa• Francis D. Kalakowski • Terry Katz • Donna Kauffman • Claudette Marie Latsko • Daniel T. Lewis • PaulB. Maasen • Victoria Mannes • Jean M. Marchesi • Jean C. Martin • Grant Arden McAllister • Georgia KayMcKinnon • Ralph Mehan • Bruce Miyawaki • Patricia Monte • Richard F. Morvay • Margaret Muirhead• Alison White Muschinsky • Michael “Leo” Myers • Douglas Brown Nelson • Beverly Kay O’Connor •Arlene O’Donnell • Alfred Ottolino • Bruce E. Packham • Ashley Panei • William Robert Park • Richard“Rick” Parker • Gilbert Pedersen • Stephen John Pehar • Shuyan Peng • Susan Peterson • William V.Pfefferle • Kieran Pillion • Lawrence Powell • Hedy Raimundo • Marcia E. Resnik • Jon Reuscher •Georgeana Rippner • William C. Roberts • William “Bill” Thomas Roberts, III • Marianna Romanowski• Herbert Russ • Thomas R. Sharp • Sylvia Sheldon • Nicole M. Shoemaker • Kenneth R. Silk • Ted Simon• Leon A. Soltyslak, Jr. • Michael Sortino • Charles E. Speights • Richard Walter Spigel • Branch Sternal •Daniel Stevens • Nathaniel Stevenson, Jr. • James R. Stewart, Sr. • Patricia Davey Struck • ElizabethSullivan • John A. Taylor • Louis Thomas • Deborah Ann Thompson • William J. Toole • Joseph G. Trimboli• Rita B. Voit • Andrew Blight Walker, Sr. • Timothy Walsh • Stuart Weinstein • Neal Wingfield • MarshallBen Willis, Sr. • Gary Wilson • Ruth E. Zager

MEMORIAL FUNDS

Honor or memorialize your loved one at: www.mds.foundation.org/donate orcontact us at 800-MDS-0839 (within US), 609-298-1035 (Outside US).

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MEMORIAL DONATIONS HAVE BEEN RECEIVED IN THE NAME OF:

LIVING ENDOWMENTS

Living Endowment Donations Have Been Made in Honor of:

Steve BechtelSubmitted by: Robert De Rienzo

Jonathan Cohn Submitted by:

Dr. Robert & Ruth CohnFamily Foundation

Palm Beach Gardens, FLDr. Amy DeZern

Submitted by:Dr. Laurence & Ann Brody Cove

Bethesda, MD

John (Jack) Lawlor Submitted by:Kevin Lawlor

Samira MolabecirovicSubmitted by:

Sanibel/Captiva Trust CompanySanibel Island, FL

Bonnie Reed Submitted by:

J.P. and Roslyn CarneyAlexander, NC

Sagar SharmaSubmitted by:

Gouri Shanker, Clemmons¸ NCRonald Solberg

Submitted by: Ronda Solberg Dr. Richard Stone

Submitted by:Beverly R. Bobroske, Bristol, CT

Carol’s SisterSubmitted by:

James and Carol Chappell, Dewey, AZ

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NEW CLINICAL STUDY IN MDS PEVONEDISTAT-2001

Azacitidine Versus Single-Agent Azacitidine in Patients with Higher-Risk Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), and Low-Blast Acute Myelogenous Leukemia (AML).

Takeda Pharmaceuticals International Co. is currently enrolling patients for a Phase 2 clinical trial of the

chronic myelomonocytic leukemia and low-blast acute myelogeneous leukemia.

The study will enroll approximately 117 participants. Once enrolled, participants will be randomly assigned

• Pevonedistat 20 mg/m2 and azacitidine 75 mg/m2 combination• Single-agent azacitidine 75 mg/m2

• 18 years of age or older• Patients have intermediate, high, or very high-risk MDS based on the Revised International Prognostic Scoring System (IPSS-R), a standard prognostic tool, or have CMML•

In order to refer a patient with MDS, CMML, or low-blast AML for enrollment to this study and review eligibility criteria, physicians/health care providers should visit www.clinicaltrials.gov (NCT02610777)

Contact: 1-877-674-3784; [email protected]

Pevonedistat is an investigational agent and is not approved by the FDA or other regulatory agencies worldwide as a treatment for any indication.

Takeda Oncology is a trademark of Takeda Pharmaceutical Company Limited. Millennium Pharmaceuticals, Inc. is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. ©2016 Millennium Pharmaceuticals, Inc.

www.onconova.com

INSPIRE Phase 3 Trial

INternational Study of Phase III Intravenous RigosErtib

A Phase III, International, Randomized, Controlled Study of Rigosertib versus Physician’s Choice of Treatment in Patients with Myelodysplastic Syndrome after

Failure of a Hypomethylating Agent

Primary Endpoint: Overall survival

in the intention-to-treat population, or in the subgroup with very high risk per the Revised International

Prognosis Scoring System (VHR-IPSS-R)

International Trial: More than 100 trial sites

For additional information on this study, please call the INSPIRE help line at

1-267-759-3676 or visit www.clinicaltrials.gov, identifier: NCT02562443

Rigosertib is an investigational agent and is not approved by the FDA or other regulatory agencies worldwide as a treatment for any indication.

Rigosertib prior clinical data: Garcia-Manero G, et al. Lancet Oncology. 2016;17(4):496-508.

Rigosertib mechanism of action: Athuluri-Divakar et al., Cell. 2016;165,643–655

For MDS Patients

After HMA failure

Eligibility:

MDS subtypes RAEB-1, RAEB-2, or RAEB-t Progression or failure

to respond to HMA HMA treatment

< 82 years of age

Primary Endpoint:

Overall Survival Physician’s Choice of

Treatment + best supportive care

N = 75

2:1 R A N D O M I Z A T I O N

Rigosertib + best supportive care

N = 150

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WillWeexhaust all possibilities.

Celgene Patient Support® provides free and personalized assistance with patients’ access and reimbursement needs.

With continual communication and consistent follow-through, your dedicated Celgene Patient Support® Specialist will streamline access to Celgene products by helping you and your patients with:

Benefits investigation

Prior authorization

Appeal support

Medicare

Co-pay assistance – Celgene Commercial Co-pay Program – Co-pay assistance through third-party organizations

Prescription status

Celgene free medication program

Celgene products and restricted distribution programs

To Contact Celgene Patient Support®:

Call: 1-800-931-8691

E-mail: [email protected]

Fax: 1-800-822-2496

Visit: www.CelgenePatientSupport.com

Monday through Friday, 8:00 AM to 7:00 PM ET

4 out of 5 patients who requested assistance from Celgene Patient Support ® received their medication.

Celgene Patient Support® is a registered trademark of Celgene Corporation.© 2013 Celgene Corporation 09/13 US-CELG110059(1)

We will…because patients are our priority.

WillWeexhaust all possibilities.

Celgene Patient Support® provides free and personalized assistance with patients’ access and reimbursement needs.

With continual communication and consistent follow-through, your dedicated Celgene Patient Support® Specialist will streamline access to Celgene products by helping you and your patients with:

Benefits investigation

Prior authorization

Appeal support

Medicare

Co-pay assistance – Celgene Commercial Co-pay Program – Co-pay assistance through third-party organizations

Prescription status

Celgene free medication program

Celgene products and restricted distribution programs

To Contact Celgene Patient Support®:

Call: 1-800-931-8691

E-mail: [email protected]

Fax: 1-800-822-2496

Visit: www.CelgenePatientSupport.com

Monday through Friday, 8:00 AM to 7:00 PM ET

4 out of 5 patients who requested assistance from Celgene Patient Support ® received their medication.

Celgene Patient Support® is a registered trademark of Celgene Corporation.© 2013 Celgene Corporation 09/13 US-CELG110059(1)

We will…because patients are our priority.

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NEW CLINICAL STUDY: IMerge Lower-Risk MDSCurrent Status: Part 1 recruitment complete; Part 2 is not yet open for recruitment. For

additional details, refer to the Geron press release (12Sep2016) at

http://ir.geron.com/phoenix.zhtml?c=67323&p=irol-newsArticle&ID=2201055.

Janssen Research & Development, LLC is conducting a Phase 2/3 clinical study referred to as

“IMerge”, with the study drug Imetelstat, which is a first-in-class telomerase inhibitor. With its

novel mechanism of action, Imetelstat may provide clinical benefit to MDS patients. In this study,

Imetelstat is administered as a 2-hour intravenous infusion every 28 days.

IMerge is a study for people with MDS who need blood transfusions due to anemia (low red

blood cell counts). People with low or intermediate-1 risk MDS that has relapsed or is refractory

to Erythropoiesis-Stimulating Agents (ESAs) treatment are enrolled in the study. This study is

being conducted at multiple hospitals and institutions around the world, in approximately 80

sites globally.

For more information about this clinical study, please visit

www.clinicaltrials.gov (NCT02598661)

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2017MAY 3-6Valencia, Spain

ADVANCING RESEARCH & PATIENT CARE


MDS 2017 Symposium Secretariat: c/o Kenes InternationalEmail: [email protected] MDS Foundation Contact: US number: 1-800-MDS-0839 Outside the US: 1-609-298-1035


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