Allogeneic hematopoietic stem cell transplantation (allo-HSCT) with reduced intensity conditioning regimens in children and adolescents with very high risk acute lymphoblastic leukemia (VHR ALL)

Cellular Therapy and Transplantation

Boris V. Afanasyev¹  Natalia E. Ivanova¹  Elena V. Babenko¹  Sergey N. Bondarenko¹  Alexander L. Alyanskiy¹  Elena V. Semenova¹  Natalia V. Stancheva¹  Sergey N. Shiryev¹  Ludmila S. Zubarovskaya¹ 

关键词: reduced intensity conditioning;    acute lymphoblastic leukemia;    children and adolescents.;   

DOI  :  10.3205/ctt-2010-No9-abstract12

学科分类：肿瘤学

来源: Universitaetsklinikum Hamburg - Eppendorf / University Medical Center Hamburg - Eppendorf

【 摘 要 】

Theaim:Tocomparetheefficacyofreducedintensityconditioning(RIC)andmyeloablativeconditioning(MAC)forallo-HSCTinchildrenandadolescentssufferingfromVHRALL.Patientsandmethods:88ALLpatients(pts)withamedianageof12(range,1–21)underwentallo-HSCTbetween12/2000and12/2009.Theindicationforallo-HSCTinchildrenandadolescentswasVHRALL:lateresponderonchemotherapy(inductionfailure),poor-riskcytogenetics(t(9:22),t(4:11)),andMRD(gt;10-2),infantswith11q23rearrangement,shortfirstremission,primaryresistance,orresistantrelapse.RICallo-HSCTwasperformedin24pts(RIC-group):13ptswereinIorIIcompleteremission(CR),and11ptswereinresistantrelapse.TheindicationforRICallo-HSCTwaspoorperformancestatus,organdysfunctionduetoprevioustherapyorinfectioncomplicationatthemomentofallo-HSCT.MACwasusedin64pts(MAC-group):36ptswereinIandIICRatthemomentofHSCT,28ptswereIIIandIVCR,orinresistantrelapse.RICconsistedofFlu150mg/m2/d+Mel(140mg/m2/d)±ATGorFlu150mg/m2/d+Bu8mg/kg±ATG;MACconsistedofBu16mg/kg(orTreo36-48mg/m2)+Cy120mg/kg±ATG.Allo-HSCTfrommatchedrelateddonorswasperformedin22pts(RIC,n=6),andfrommatchedunrelateddonorsin62pts(RIC,n=18).Results(table1,2):IntheRIC-group,thegranulocyteengraftmentgt;=0,5x109/lwasonD+18(inrangesD+13–31).ForptsinIorIICRatRICallo-HSCT9of13arealive.Overall7-yearsurvival(OS)anddisease-freesurvival(DFS)were69%and45%,respectively.Fourptsdiedwithin100days:infection(3),andaGVHD(1).Relapseoccurredin2pts(15%):bothrelapsedptsachievedCRafterchemotherapy+DLIin1stpt,andimmunosuppressionwithdrawalin2ndpt.CRwasachievedin4of11ptsafteralloHSCTatresistantrelapse.But1-yearOSwas0%.Patientsdiedfrominfection(3),aGVHD(1),anddiseaseprogression(7).MAC-group:granulocyteengraftmentgt;=0,5x109/lwasonD+21(inrangesD+10–49).Eighteenof36ptsareinCRafterMACallo-HSCTinIorIICR.Overall7-yearsurvival(OS)andDFSwere47%and39%,respectively.11ptsrelapsedafterMACallo-HSCT(30%),but2ofthemachievedCRafterchetmotherapy+DLI.Nineptsdiedfromrelapse:aGVHD,6;infection,1;transplantrelatedtoxicity,1;andnon-engraftment,1.Fourfrom28ptsafterMACallo-HSCTinrelapseeitherIIIorIVCRareinCR(14–101months;median53months).Otherptsdiedofrelapse(12),infection(8),andaGVHD(4).Conclusion:RICallo-HSCTofVHRALLinCRpts≤21yoiseffectiveandcomparablewithMACallo-HSCT.TheseresultsmakewayfornewapproachesforptsinVHRALLinCR,indicatetheirsensitivitytoimmunoadoptivetherapyandproducethebaseforclinicaltrials.Table1.Outcomesafterallo-HSCTConditionregimeStatusatthemomentofallo-HSCT(n)Relapsen(%)TRMn(%)1year-OS7-OS1-EFS7-EFSRICIorIICR(13)2(15)4(30)69%69%68%45%Relapse(11)7(64)4(36)0000MACIorIICR(36)11(31)9(25)68%47%68%39%Relapse(28)12(43)12(43)20%14%20%1Table2.Complicationafterallo-HSCTRIC(%)MAC(%)AcuteGVHDgrade1–45553ChronicGVHD8854Infection8883Hepatotoxicity5030Neurotoxicity2525Hemorrhagic1333

【 授权许可】

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