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Blood andMarrowTransplant

KylieLepicMD,FRCPCMcMasterUniversity/HamiltonHealth

Sciences

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Ø KeyNewsThisYearØ KeyNewsoutofASH2017

• Sessions• Abstracts

AGENDA

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HotTopicsinBloodandMarrowTransplant• Choosingthebestdonor• Haploidentical transplantation• Survivorshipmodels• NeweragentsforthetreatmentofGVHD• CART-Cells

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Haploidentical T-Repleted StemCellTransplantation(SCT)HasComparableSurvivalto10/10and9/10UnrelatedSCTin

Poor-CytogeneticsRiskAcuteMyeloidLeukemiainFirstCompleteRemission:AStudyonBehalfoftheAcute

LeukemiaWorkingParty(ALWP)oftheEuropeanSocietyforBloodandMarrowTransplantation(EBMT)

FrancescaLorentino,MD

OralAbstract852Session:732.ClinicalAllogeneicTransplantation:Results:

DonorSelectionintheHaplo TransplantEraMonday,December11,2017:5:45PM

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Lorentino etal.• RetrospectivelycomparedtheoutcomesofpoorriskAMLpatientsinCR1

receiving:– T-cellrepletehaploSCT (74)– 10/10matchedunrelateddonor(MUD)SCT(433)– 9/10HLA-matchedUDSCT(123)

• PoorriskAMLwasdefinedasthepresenceof:– complexkaryotype– monosomal karyotype– inv(3)/t(3;3)– -5ordel(5q)– -7orabn(7q)– t(v;11)(v;q23)– abn(17p)– t(6;9)– t(9;22)

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Results:• LFSandOSat2yearswerenotsignificantlydifferentbetweenhaploSCT,

10/10UDSCTand9/10UDSCT(53±12%and59±12%,43±5%and50±6%,44±9%and50±9%,respectively,p=0.5andp=0.5,respectively)

• 100-daycumulativeincidence(CI)ofgrade≥2aGvHD wassimilar (33±11%forhaplo,30±4%for10/10UDand34±9%for9/10UD,p=0.6)

• 2-yCIofcGvHD wassimilar (35±12%forHaploSCT,36±4%for10/10UD,36±9%for9/10UD,p=0.8)

• The2-yCIofNRMwasnotsignificantlydifferent19±8%afterhaploSCT,18±4%after10/10UDSCTand18±6%after9/10UDSCT(p=0.9)

• Relapseincidencewasnotsignificantlydifferent,witha2-yCIof27±9%forhaploSCT,39±5%for10/10UDSCTand37±9%for9/10UDSCT(p=0.3)

Conclusions:• haploSCT recipientsexperiencedcomparableoutcomeswithrespectto

10/10and9/10HLA-matchedUDforpoorriskAML

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TakeHomeMessage:• HaploSCT outcomesaresimilartoconventionaldonoroutcomesforpoorriskAMLwhichisconsistentwithotherliteraturefordifferentdiseasegroups

• ShouldweconsiderusinghaploSCT insteadofconventionaldonorstogetthishighriskpopulationtotransplantfaster?

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ComparisonofChronicGraft-Versus-HostDiseaseSeverityandFunctionalStatusafterCordBlood,HaploidenticalRelatedand1-AlleleMismatchedUnrelatedDonor

HematopoieticCellTransplantationGiancarloFatobene etal

OralAbstract73Session:722.ClinicalAllogeneicTransplantation:Acuteand

ChronicGVHD,ImmuneReconstitution:PathobiologySaturday,December9,2017:7:45AM

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Fatobene etal.• RetrospectivelyanalyzedtheincidenceofcGVHD and

manifestationsassociatedwithseveremorbidityandpoorfunctionaloutcomesamongrecipientswithalternativeHCTdonors

• Donorsincluded4-6/6-HLA-matchedsingleordoublecordbloodunits(UCB),TcellrepleteHLA-haploidenticalmarroworstemcells,1-allelemismatching(1-mMUD)stemcellsforanydiagnosisbetween2006- 2015

• 129ofthe396alternativedonorHCTrecipientsdevelopedcGVHD,andwereincludedinthestudy

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Results:• cGVHD developedin18%ofUCBrecipients,24%R-HAPLO

recipientsand55%1-mMUDrecipients• TheCIofanymanifestationofseveremorbidityat3yearsaftera

cGVHD diagnosiswassignificantlylowerinUCB(14%)andR-HAPLO(23%)comparedtothe1-mMUDgroup(58%)[HR0.13(95%CI0.1-0.4),p=<0.0001,andHR0.31(0.1-0.7),p=0.007,respectively]

• Comparedtothe1-mMUDgroup,morerecipientsofUCB(68%vs.35%)returnedtowork/schoolat3yearsaftercGVHD [HR2.54(1.1-5.7),p=0.02],andasimilartrendwasobservedinR-HAPLO(62%vs.35%[HR2.38(1.0-5.9),p=0.06)]

• TheCIofdiscontinuedsystemicimmunosuppressionat3yearswassignificantlylowerinthe1-mMUD(15%)comparedtotheUCB(45%)andR-HAPLO(50%)groups[HR3.96(1.9-8.4),p=0.0003,andHR4.93(2.2-11.1),p=0.0001,respectively]

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Conclusions:• Comparedto1-mMUDgroup,UCBandR-HAPLOHCTrecipientswerelesslikelytodevelopcGVHD

• AmongthosewithcGVHD,UCBandR-HAPLOHCTrecipientswerelesslikelytodevelopmanifestationsofseveremorbidity,hadashorterdurationofsystemictreatment,andhigherlikelihoodofresumingworkorschool,suggestingbetterQoL comparedto1-mMUDHCTrecipients

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TakeHomeMessage:• cGVHD andassociatedmorbidityareimportantoutcomespostbmt andhigherratesinsinglemismatchedUDtransplantsmakethisdonortypelessideal

• Shouldwenolongerusesinglemismatchedunrelateddonors?

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Analysisof10,4628/8HLA- MatchedUnrelatedDonorTransplantsCouldNot

IdentifyaDonorSelectionScore,AsYoungerAgeIstheOnlySignificantDonor

CharacteristicAssociatedwithSurvivalBronwen E.Shawetal.

OralAbstract848Session:732.ClinicalAllogeneicTransplantation:Results:

DonorSelectionintheHaplo TransplantEraMonday,December11,2017:4:45PM

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Shawetal.• Purposewastodevelopandvalidateadonorselectionscorethatprioritizesdonor

characteristicsassociatedwithbettersurvivalin8/8HLA-matchedURDtransplantation• Studied2largeCIBMTRpatientdatasets:HCTfrom1999-2011(n=5952)and2012-2014

(n=4510)• Patientswereadults(>18),transplantedforacutemyelogenous leukemia(AML),acute

lymphocyticleukemia(ALL),chronicmyelogenous leukemia(CML),ormyelodysplasticsyndrome(MDS)

• twoindependentmodelswerebuiltandtestedwithdonorcharacteristics:– HLA-DQB1matching,HLA-DPB1matching(usingtheT-cellepitopematching

categorization)– Age– Sexmatching– Parity– CMVmatching– ABOmatching– racematching

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Results:• Significantnegativeassociationswithsurvivalforthreedonorriskfactors:

– non-permissiveDPB1matching(HR1.13;95%CI1.01,1.26;p-value=0.032)– olderdonorage(asalineareffect,HR1.07perdecadeincreaseinage;95%CI1.02,

1.12,p-value=0.004),– CMVmismatchingforCMV+recipients(HR1.14;95%CI1.02,1.27;p-value=0.022)

• Basedontheseresultsadonorriskscorewasconstructed,howeverthisscorewasnotvalidatedinthefirsttestingsetandnoneoftheindividualcomponentdonorfactorswassignificantlyassociatedwithworseoverallsurvival

• Inthesecondtestingsetonlydonoragewassignificantlyassociatedwithworsesurvival,andwasvalidated

• Quantifiedtheimpactofdonorageinthevalidationsetofthesecondcohortandfoundthatchoosingadonor2,5,10or20yearsolderwasassociatedwitha1%,2%,3%or7%decreasein2yearOS,adjustedforpatientcharacteristics

Conclusion:• Inthestudyofover10,000URDtransplantstheonlydonorcharacteristicassociatedwith

bettersurvivalwasyoungerage,with2-yearsurvivalbeing3%betterwhenadonoris10yearsyounger

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TakeHomeMessage:• Manydonorfactorsareconsideredduringselectionhoweverageremainstheonlyfactorconsistentlyshowntoimpactsurvivalinlargeregistrystudies

• Shouldthisimpactdonorrecruitment?

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Busulfan Fludarabine (BU-FLU)ComparedtoThiotepaBusulfan Fludarabine (TBF)forAllogeneicTransplantsin

AcuteMyeloidLeukemia(AML)orRefractoryAnemiawithExcessBlasts(RAEB)inRemission

FedericaSoraMDetal.

OralPresentation909Session:721.ClinicalAllogeneicTransplantation:

ConditioningRegimens,Engraftment,andAcuteTransplantToxicities:PreparativeRegimens

Monday,December11,2017:6:45PM

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Sora etal.• ComparedconditioningwithBusulfan andFludarabine (Bu-

FLU)vs.Thiotepa,Busulfan andFludarabine (TBF)inpatientswithAMLorMDSRAEBtransplantedbetween2008- 2017

• 78patientsreceivedtheBU-FLUregimen(busulfan 3.2mg/kg/dayx4;andfludarabine 40mg/m2/dayx4)

• 127receivedTBF(thiotepa 5mg/kgx2,busulfan 3.2mg/kg/dayx3,fludarabine 50mg/m2x3)

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Results:• 5-yearcumulativeincidenceofTRMwas25%and9%forBU-FLU

andTBF(p=0.007)• 5-yearcumulativeincidenceofleukemiarelapserelateddeaths

(RRD)was33%and9%(P=0.008)• 5-yearactuarialsurvivalwas41%(26-56%)forBU-FLUand82%(74-

90%)(p=0.000)forTBF• InamultivariateCoxanalysistheuseofTBFreducedtheriskof

deathascomparedtoBU-FLU(RR0.3,range0.10-0.89,p=0.01)aswellasTRM(RR0.17forTBFvsBU-FLU,p=0.02)

Conclusions:• PatientsreceivingconditioningTBFhadsuperiorsurvivalcompared

toBU-FLUduetoacombinationofreducedtoxicityandreducedrelapse

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TakeHomeMessage:• IdealconditioningregimenshavelowregimenrelatedtoxicityandtreatmentrelatedmortalitybutstillhavediseaseactivityandTBFshowspromiseinreachingthosecriteria

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Thankyou!

EnjoyAtlanta,GAandASH2017