BoneMarrowTransplantforMDSPatients
LoriMufflyMDMSAssistantProfessorofMedicine
DivisionofBloodandMarrowTransplantationStanfordUniversity
• BMT:Thebasics
• BMTforMDS:Theevidence
• InnovativeapproachestoBMTforMDS
WhatisBoneMarrow?
WhatisanAllogeneicBMT?• BMT=bonemarrow(orstemcell)transplant
• Allogeneic=fromaDonor– Someone“immunologically”compatible
• Transplant=Replacerecipient(patient’s)bonemarrowwiththedonor’sbonemarrow– ReplaceRBC,platelets,WBC
HowDoWePerformAllogeneicBMT?
• Medicaltransplant=NOSURGERY
• Howdowecollectdonorstemcells?– BonemarrowharvestinOR– Usestemcellboosterandcollectviaperipheralveins
STEP1:Conditioning/Prep:PreparesBodyto
AcceptDonorStemCells
STEP2:Infusionof
DonorStemCells
STEP3:StemCells“Engraft”
STEP4:Preventsideeffects&re-evaluatemarrowtoensureNOMDS
7-14daysAnhour14-21daysManymonths
WhyDoWePerformAllogeneicBMT?
• Transplant=Replacerecipient(patient’s)bonemarrowwiththedonor’sbonemarrow– ReplaceRBC,platelets,WBC
• New(donor)immunesystemcanbeverypowerfulatcontrollingbloodcancercellsCUREMDS
NewImmuneSystem
NumberofallogeneicBMTs/yr inUShasdoubledinrecentyears
TrendsinAllogeneicBMTUtilizationforAdults≥70Years,byDisease
AbsoluteNo.HCTs≥
70Years
0
20
40
60
80
100
120
140
160
AML MDS/MPS Non-Hodgkinlymphoma Others
MufflyetalBlood2017
• Historically,patients65andolderwithMedicaredidnothavecoverageforBMTforMDS.
• OnAugust4th 2010,theCentersforMedicareandMedicaidservices(CMS)establishedcoverageforBMTforMDSthroughcoveragewithevidencedevelopment(CED).
• ACenterforInternationalBoneMarrowTransplantResearch(CIBMTR)studycomparingoutcomesofpatients55-64vs.65andolderwasapprovedinDecember2010.
WhyisAllogeneicBMTforMDSontheRise?
Atallah etalBlood2017
• Thestudycomparedtheoutcomesof:– 688patientsaged65andolderand– 592patientsaged55-64– whounderwentallogeneicBMTforMDSfrom2010-2014
• Survivalat100daysandattwoyearsfollowingBMTforMDSpatientsaged65andolderiscomparabletopatientsaged55to64.
• AgealoneshouldnotbeadeterminantwhenconsideringBMTforpatientswithMDS.
MedicareCoveragewithEvidenceDevelopmentMDSBMTStudy
Atallah etalBlood2017
HowDoWeDetermineWhichMDSPatienttoTransplant?
DeWitteetalBlood2017
HowDoWeDetermineWhichMDSPatienttoTransplant?
DeWitteetalBlood2017
WhatAreOutcomesafterBMTforMDS?
• Ingeneral….
– 30-40%ofintermediate/highriskMDSpatientswillbecuredfollowingallogeneicBMT
BUT– Somepatientswillhaveseriousmorbidity/mortalityfromthetransplantprocessandsomepatientswillhaverecurrenceofprogressionofMDSafterBMT
HowCanWeImproveAllogeneicBMTforMDS?
STEP1:Conditioning/Prep:PreparesBodyto
AcceptDonorStemCells
STEP2:Infusionof
DonorStemCells
STEP3:StemCells“Engraft”
STEP4:Preventsideeffects&re-evaluatemarrowtoensureNOMDS
AlterthepreptotargetMDScells
Engineeroroptimizedonor
stemcells
1)ReducetoxicityofallogeneicBMT2)AdditionalMDStargetingpost-
BMT
PhaseI/IIClinicalTrialofanMDSStemCellTargetingAntibodyPlusLowIntensityConditioningfor
PatientswithMDSundergoingAllogeneicBMT
ReducingBMTComplications
• PhaseIIIclinicaltrialconductedacrosstheUSaimingtoimprovepost-BMToutcomesforpatientswithMDSandacuteleukemiabyreducingtransplanttoxicity.
Conclusions
• AllogeneicBMTisanimmunotherapythatoffersapotentialforcureforintermediate/highriskMDSpatients
• TheuseofallogeneicBMTforMDS(andforolderadults)isrising
• NewandinnovativeapproachestoBMTareneededtofurtherimproveoutcomes
