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