多发性骨髓瘤的造血干细胞移植78张课件

多发性骨髓瘤的造血干细胞移植31、别人笑我太疯癫，我笑他人看不穿。(名言网)32、我不想听失意者的哭泣，抱怨者的牢骚，这是羊群中的瘟疫，我不能被它传染。我要尽量避免绝望，辛勤耕耘，忍受苦楚。我一试再试，争取每天的成功，避免以失败收常在别人停滞不前时，我继续拼搏。33、如果惧怕前面跌宕的山岩，生命就永远只能是死水一潭。34、当你眼泪忍不住要流出来的时候，睁大眼睛，千万别眨眼!你会看到世界由清晰变模糊的全过程，心会在你泪水落下的那一刻变得清澈明晰。盐。注定要融化的，也许是用眼泪的方式。35、不要以为自己成功一次就可以了，也不要以为过去的光荣可以被永远肯定。多发性骨髓瘤的造血干细胞移植多发性骨髓瘤的造血干细胞移植31、别人笑我太疯癫，我笑他人看不穿。(名言网)32、我不想听失意者的哭泣，抱怨者的牢骚，这是羊群中的瘟疫，我不能被它传染。我要尽量避免绝望，辛勤耕耘，忍受苦楚。我一试再试，争取每天的成功，避免以失败收常在别人停滞不前时，我继续拼搏。33、如果惧怕前面跌宕的山岩，生命就永远只能是死水一潭。34、当你眼泪忍不住要流出来的时候，睁大眼睛，千万别眨眼!你会看到世界由清晰变模糊的全过程，心会在你泪水落下的那一刻变得清澈明晰。盐。注定要融化的，也许是用眼泪的方式。35、不要以为自己成功一次就可以了，也不要以为过去的光荣可以被永远肯定。多发性骨髓瘤的造血干细胞移植

首都医科大学附属北京朝阳医院北京市多发性骨髓瘤医疗研究中心为什么要移植？多发性骨髓瘤的造血干细胞移植31、别人笑我太疯癫，我笑他人看多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细胞移植78张课件BarlogieB,etal.Cancer.2008;113:355–359..持久CR是长生存的最重要因素生存率0123456SUS-CR:获得并维持CR状态NON-CR:从未获得CR状态LOS-CR:获得但失去CR状态年数100%80%60%40%20%0%BarlogieB,etal.Cancer.2008;113:355–359..P-value:avsb<0.0001,bvsc<0.0001,avsc<0.0001abcBarlogieB,etal.Cancer.200以新药为基础的诱导方案的疗效诱导方案以新药为基础的诱导方案的疗效诱导方案ASCT能进一步提高新药诱导后的疗效*Post-transplantdatanotavailableHarousseauetal.ASH/ASCOsymposiumduringASH2008Rajkumaretal.ASCO2008(Abstract8504);ASH2008(jointASH/ASCOsymposium)Lokhorstetal.Haematologica2008;93:124–127Sonneveldetal.ASH2008(Abstract653);IMW(Abstract152)Cavoetal.ASH2008(Abstract158);IMW2009(Abstract451)新药诱导治疗和ASCT的作用是互补的,而不是作为二选一的治疗手段≥VGPR（%）61%49%59%76%*44–50%诱导治疗后移植后VADVDRDRdTADPADVTD*15-16%39%42%24%33%42%62%ASCT能进一步提高新药诱导后的疗效*Post-transp多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细胞移植78张课件以硼替佐米为基础的诱导方案IFM2005-01HOVON-GMMGVDvsVADPADvsVAD患者数223vs218150vs150ASCT前反应，%CR6vs1*5vs0*>VGPR38vs15*33vs12*>PR78.5vs63*80vs64*ASCT后反应，%CR16vs9*15vs4*>VGPR54vs37*59vs47*>PR80vs7792vs77**具有显著性差异*对于IFM2005/01，首次移植后的反应率表示为总体反应率，包含第二次移植反映率。>VGPR的反应率在VD组为68%，VAD组为47%；CR/nCR在VD组为39.5%，VAD组为22.5%。1.HarousseauJL,etal.JCO2010inpress.2.SonneveldP,etal.IMW2009:[abstract152].以硼替佐米为基础的诱导方案IFM2005-01HOVON-G移植的时机目前倾向于作为巩固治疗在疾病早期进行，避免在疾病复发时一般情况差、肾功能不全、年龄增加、过多骨骼破坏以及发生MDS的高风险。

移植的时机目前倾向于作为巩固治疗在疾病早期进行，避免在疾病复病人的年龄多限定在65岁以下，但也有超出该年龄病人的报道。肾功能不全不是移植的禁忌症，一般可将马法兰的剂量调整至140mg/m2;如病人有低蛋白血症，可将马法兰的剂量进一步调整至70-100mg/m2。

病人的年龄多限定在65岁以下，但也有超出该年龄病人的报道。KumaretalASH2009(Abstr956）VRD×5StemCollectionR×12mASCTatrelapseVRD×3复发前和复发后进行ASCT疗效相同IFM-DFCL2009ASCT在复发前还是在复发后进行？

VRD×3StemCollectionASCTVRD×2R×12mKumaretalASH2009(Abstr956小结患者的生存与缓解程度有关化疗可以提高缓解率及缓解程度二次移植优于单次移植新药的应用可以进一步提高疗效早期与晚期移植的疗效相似小结患者的生存与缓解程度有关干细胞动员的问题干细胞动员的问题HighrateofstemcellmobilizationfailureafterthalidomideandoralcyclophosphamideinductiontherapyformultiplemyelomaHWAuner,LMazzarella,LCook,RSzydlo,FSaltarelli,JPavlu,MBua,CGiles,JFApperleyandARahemtullaDepartmentofHaematologyHammersmithHospitalImperialCollegeHealthcareNHSTrust,London,UKBoneMarrowTransplantation(2010),1–4,epubHighrateofstemcellmobiliz多发性骨髓瘤的造血干细胞移植78张课件Figure1InductiontherapywithCYandthalidomidewithdexamethasone(CTD)impairsthestemcellcollectionyieldandincreasesthenumberofapheresisproceduresrequired.(a)BarsshowthemediannumberofCD34tcells/kgcollectedoverall,onthefirstapheresisday,andperapheresisprocedure.(b)BarsshowthepercentageofpatientsundergoingX2apheresisprocedures.Figure1Inductiontherapywit多发性骨髓瘤的造血干细胞移植78张课件预处理预处理HowtoimprovetheefficacyofconditionregimensMelphalan200mg/m2…..thegoldstandardMelphalan+Busulphan….maybesuperiorMelphalan+Bortezomib…70%≧VGPR(35%CR)(1mg/m2D-6-3+1+4)Melphalan+Bortezomib…53%≧VGPR(1.3mg/m2D-1or+1)HowtoimprovetheefficacyofBUandCYasconditioningregimenforautologoustransplantinpatientswithmultiplemyelomaGTalamo,DFClaxton,DWDougherty,CWEhmann,JSivik,JJDrabickandWRybkaBoneMarrowTransplantProgram,PennStateMiltonSHersheyCancerInstitute,Hershey,PA,USABoneMarrowTransplantation(2009)44,157–161BUandCYasconditioningregi多发性骨髓瘤的造血干细胞移植78张课件Figure1OSofmultiplemyelomapatientstreatedwiththeBU/CYregimenandASCT(n79),fromday0ofASCT.Thinlinesindicatethe95%confidenceinterval.Figure2PFSofmultiplemyelomapatientstreatedwiththeBU/CYregimenandASCT(n79),fromday0ofASCT.Thinlinesindicatethe95%confidenceintervalFigure3PFSofmultiplemyelomapatientstreatedwithoral(n13,continuousline)vsi.v.BU(n66,dottedline),fromday0ofASCT.Figure4OSofmultiplemyelomapatientstreatedwiththeBU/CYregimenandASCTcarriedout‘upfront’,thatis,infirstremission(n62,continuousline),vsASCTcarriedoutas‘salvagetherapy’,thatis,ondiseaseprogression/relapse(n17,dottedline).SurvivaliscalculatedfromthetimeofMMdiagnosis.Figure1OSofmultiplemyelom移植后的巩固与维持治疗移植后的巩固与维持治疗2009ASHAbstract351APhaseⅢStudyofDoubleAutotransplantationIncorporatingBortezomib-Thalidomide-Dexamethasone(VTD)orThalidomide-Dexamethasone(TD)forMultipleMyeloma:SuperiorClinicalOutcomeswithVTDComparedtoTDMicheleCabvo,PaolaTacchetti,FrancescaPatriarca,etal.sergnoliInstituteofHematology,BolognaUniversitySchoolofMedicine,Bologna,ItalyItalianMyelomaNetworkGIMEMA,Italy2009ASHAbstract351APhaseⅢStudyDesign.REGISTRATIONThalidomide+DexT100-200mgpodays1-21/D40mgdays1,2,4,5,8,9,11,12q21x3cyclesBortezomib+t+DB1.3mg/㎡days1,4,8,11,Q21x3cyclesDoubleASCTMelphalan200mg/㎡TDConsolidationT100mgpodays1-35/D320mgpercycleq35x2cyclesVTDConsolidationB1.3mg/㎡days1,8,1522q35/T100mgpodays1-35/D320mgpercycleQ35,Bx2cyclesMaintenanceDexStudyDesign.REGISTRATIONThaliPatientCharacteristics.VTD(n=241)TD(n=239)Age(years)56.33±6.8855.86±7.41StageISS(%)ⅠⅡ+Ⅲ107(44)134(56)107(45)132(55)Β2-MG(mg/L)3.81±2.483.83±2.14Albumin(g/dL)3.83±0.644.17±3.97Creatinine(mg/dL)1.01±0.301.01±0.31Hb(g/dL)11.10±1.9111.24±1.96Plts(X10/L)243.69±89.06235.86±78.04BMPCmean±SD(%)52.42±23.1952.78±24.15Geneticabnormalities(byFISHin93%ofpts)Del(13q)pos(%)del(13q)alonet(4:14)pos(%)del(17p)pos(%)47[30]18746[26]2089PatientCharacteristics.VTD(n=BestResponse.VTD(%)TD(%)PCR57.2031.070.0001CR+nCR69.9151.23<0.0001≧VGPR87.7172.26<0.0001≧PR94.9188.650.01BestResponse.VTD(%)TD(%)PCR57PFSinHigh-riskCytogenetics*TDVTDPositiveNegativePositiveNegative%events3620.322.712.1%PFSat24mos53777383%PFSat30mos42596067Pvalue0.020.16*t(4;14)±del(17p)PFSinHigh-riskCytogenetics*BrJHaematol,2008,140:625–634.BrJHaematol,2008,140:625–634多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细胞移植78张课件

Mel干细胞回输

G-CSFV V V V-6-3-20+1 +4 +7V=万珂1.0-1.3mg/m2Mel=马法兰

200mg/m2

万珂-马法兰用于ASCT预处理的研究缓解率CR=31%!，VGPR=46%CR+VGPR=77%（历史对照：常规HDM预处理，ASCT后的CR+VGPR=40~50%）Rousseletal.Hematology2006;91(suppl.1),p98.EHA2006,abs0233# Mel干细胞回输 ConsolidationwithBortezomib+Thalidomide+DexPatients(n=40)withCRorVGPRfollowingASCTTreatments:4consolidationcyclesofBtz-Thal-DexResults:

--36%convertedfromVGPRtoCR

--Sixpatients(15%)achievedMolecularRemission

ConsolidationwithBortezomib+多发性骨髓瘤的造血干细胞移植78张课件清髓性异基因移植清髓性异基因移植Overallandevent-freesurvivalarenotimprovedbytheuseofmyeloablativetherapyfollowingintensifiedchemotherapyinpreviouslyuntreatedpatientswithmultiplemyeloma:aprospectiverandomizedphase3studyChristineM.Segeren,PieterSonneveld,BronnovanderHolt,etal.ErasmusMedicalCenterRotterdam(ErasmusMC)andUniversityMedicalCenterUtrecht(UMCU)fortheDutch-BelgianHemato-OncologyCooperativeStudyGroup(HOVON),TheNetherlandsBLOOD,2003,101(6):2144-51Overallandevent-freesurviva多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细胞移植78张课件TTPOSTTPOS多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细胞移植78张课件MyeloablativeBMTAuthorN(%chemo-refractory)TRMCROS(f/uyears)PFS(f/uyears)Gahrton162(46)41%44%28%(7)55%(5)Bensinger80(71)43%36%24%(4.5)20%(4.5)Gahrton334(27)BM’83-‘93356(24)BM’94-‘98133(26)PBSC’94-‘9846%30%37%60%60%54%35%(3)55%(3)57%(3)40%(3)55%(3)NRMyeloablativeBMTAuthorN(%chOverallSurvivalYearsProportion0246810120.00.20.40.60.81.0AllogeneicAutologousp=0.006OverallSurvivalYearsProportioCausesofTreatmentFailureCausesofTreatmentFailureCumulativeIncidenceofRelapse

YearsCumulativeIncidence0246810120.00.20.40.60.81.0AutologousAllogeneicp=0.02CumulativeIncidenceofRelapsAllogeneicSCTAdvangtagesStemcellsNon-contaminatedNodamageGVMeffectDisadvantagesTrxrelatedmortality>20%~40%Age&Donoravailablity10%candidatesHighmortalitywithconventionalallo…hasfavoredtheReducedIntensityConditioningregimens(RIC)…ButtheTRMisstill10%~20%;cGVHD:35%~70%&morerelapses(extramedullary)…toovercomerelapses:“TandemAuto-Allo”programAllogeneicSCTAdvang序贯自体-非清髓移植序贯自体-非清髓移植AllogenicHematopoieticStem-cellTransplantationWithReduced-intensityConditioninginPatientsWithRefractoryandRecurrentMultipleMyelomaLong-TermFollow-UpAvichaiShimoni,IzharHardan,FrancisAyuk,GeorgiaSchilling,DjordeAtanackovic,WolfgangZeller,RonitYerushalmi,AxelRolfZander,NicolausKroger,andArnonNaglerDepartmentofBoneMarrowTransplantation,ChaimShebaMedicalCenter,Tel-Hashomer,IsraelDepartmentofBoneMarrowTransplantation,UniversityHospitalHamburg,Hamburg,GermanyCancer,2010,epubAllogenicHematopoieticStem-cosPFSosPFS多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细胞移植78张课件AComparisonofAllograftingwithAutograftingforNewlyDiagnosedMyelomaBrunoB,RottaM,PatriarcaF,etal.SanGiovanniBattistaHospitalUniversityofTurintUniversityofUdine,UdineNEnglJMed2007;356:1110-20.AComparisonofAllograftingw多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细胞移植78张课件Non-myeloablativeTransplantationAuthorConditioningregimenGVHDregimenN(URD)PriorAutoTRM%CR%Gr2-4aGVHD%ChronicGVHD%OS%(yrs)KrogerMel100/Flu/ATGCSA/MTX17(82)KrogerMel100-140/Flu/ATGCSA/MTX21(21)92440381274(2)MohtyBu/Flu/ATGCSAMTX41(NR)01724364162(2)PeggsTBI/Flu/AlemtuzumabCSA/MMF20(8)0151025NR71(2)MaloneyTBI-2Gy/FluCSA/MMF54(0)542257456069(4)GerullTBI-2Gy/FluCSA/MMF52(20)01727377041(1.5)HoepfnerTBI-2Gy/FluCSA/MMF19(6)032NR37NR50(2)MaTBI-3Gy/FluCSA/MMF10(0)00306040100(1)GalimbertiTBI-2Gy/Flu;Flu/CyCSA/MMF20(0)202035253058(2)EinseleTBI-2Gy/Flu/CyCSA/MMF/ATG22(15)02327383226(2)LeeTBI-2Gy/Flu/Mel100CSA45(12)123864581336(3)GiraltMel/FluFK/MTX22(9)04132462730(2)Perez-SimonMel/FluCSA/MTX29(NR)102128415160(2)Non-myeloablativeTransplantatAuto-alloRICvsTandemAuto3studies(IFM,PETHEMA,HOVON)......Nobenefit2studies(GIMEMA,EBMT)…significantbenefit(EFS,OS)#Differencesinpatientscharacteristics,GVHDprophylaxis,&conditioningregimensmayexplainthesediscrepantresults.Auto-alloRICvsTandemAuto3异基因移植的优势异基因移植的优势AllogeneicBoneMarrowTransplantationforMultipleMyelomaAssociatedwithhighcompleteresponseratesDurablemolecularremissionsarenotedinsomepatientsTwoadvantageswhichmayreducetheriskofrelapseafterallogeneictransplantcomparedwithautologoustransplantare:infusionofatumorfreestemcellproductgraftversusmyelomaeffectHighdoseconventionalallogeneictransplantationisassociatedwithahightreatmentrelatedmortality,upto50%insomestudiesAllogeneicBoneMarrowTransplEvidencefora

GraftversusMyeloma(GVM)EffectDelayeddisappearanceofresidualdiseaseafterallogeneicBMTinsomepatientsDecreasedrateofrelapseafterallogeneicBMTcomparedwithautologousBMT40%-80%overallresponserateinpatientswithrelapsedmultiplemyelomaafterdonorlymphocyteinfusionEvidencefora

GraftversusMResponsetoCD4+DLI

N=12PreDLIMaximalResponseCurrentstatus9-persistentor6CR5CR-1RelapseProgressivedisease3PR2relapse3-CR-2CR-1relapseResponsetoCD4+DLI

N=12PreD浆细胞白细胞的移植浆细胞白细胞的移植Primaryplasmacellleukemiaandautologousstemcelltransplantationhaematologica|2010;95(5):804-9Primaryplasmacellleukemia(PCL):lessthan5%ofmalignantPCD.Ithasapoorprognosis,mediansurvivalof8-12months.Autologousstemcelltransplantationmayimprovesurvival.Aretrospectiveanalysis(EuropeanGroupforBloodandMarrowTransplantation):272patientsPCLand20844withMMundergoingfirstautologoustransplantationbetween1980and2006.Primaryplasmacellleukemiaa多发性骨髓瘤的造血干细胞移植78张课件多发性骨髓瘤的造血干细