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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