1、Brenner et al;Blood 2008;111:2521-2526无无事事件件生生存存率率%总总生生存存率率%Barlogie B,et al.Cancer.2008;113:355359.Barlogie B,et al.Cancer.2008;113:355359.P-value:a vs b0.0001,b vs c 0.0001,a vs c VGPR的反应率在的反应率在VD组为组为68%，VAD组为组为47%；CR/nCR在在VD组为组为39.5%，VAD组为组为22.5%。1.Harousseau JL,et al.JCO 2010 in press.2.Sonnevel
2、d P,et al.IMW 2009:abstract 152.Kumar et al ASH2009(Abstr 956）VRD5Stem CollectionR12mASCT at relapseVRD3复发前和复发后进行复发前和复发后进行ASCTASCT疗效相同疗效相同IFM-DFCL2009Stem CollectionASCTVRD2R12mHigh rate of stem cell mobilization failure after thalidomide and oral cyclophosphamide induction therapy for multiple myel
3、omaHW Auner,L Mazzarella,L Cook,R Szydlo,F Saltarelli,J Pavlu,M Bua,C Giles,JF Apperley and A RahemtullaDepartment of Haematology Hammersmith Hospital Imperial College Healthcare NHS Trust,London,UKBone Marrow Transplantation(2010),14,epubFigure 1 Induction therapy with CY and thalidomide with dexam
4、ethasone(CTD)impairs the stem cell collection yield and increases the number of apheresis procedures required.(a)Bars show the median number of CD34tcells/kg collected overall,on the first apheresis day,and per apheresis procedure.(b)Bars show the percentage of patients undergoing X2 apheresis proce
5、dures.BU and CY as conditioning regimen for autologous transplant in patientswith multiple myelomaG Talamo,DF Claxton,DW Dougherty,CW Ehmann,J Sivik,JJ Drabick and W RybkaBone Marrow Transplant Program,Penn State Milton S Hershey Cancer Institute,Hershey,PA,USABone Marrow Transplantation(2009)44,157
6、161Figure 1 OS of multiple myeloma patients treated with the BU/CY regimen and ASCT(n79),from day 0 of ASCT.Thin lines indicate the 95%confidence interval.Figure 2 PFS of multiple myeloma patients treated with the BU/CY regimen and ASCT(n79),from day 0 of ASCT.Thin lines indicate the 95%confidence i
7、ntervalFigure 3 PFS of multiple myeloma patients treated with oral(n13,continuous line)vs i.v.BU(n66,dotted line),from day 0 of ASCT.Figure 4 OS of multiple myeloma patients treated with the BU/CY regimen and ASCT carried out upfront,that is,in first remission(n62,continuous line),vs ASCT carried ou
8、t as salvage therapy,that is,on disease progression/relapse(n17,dotted line).Survival is calculated from the time of MM diagnosis.移植后的巩固与维持治疗移植后的巩固与维持治疗REGISTRATIONThalidomide+DexT 100-200 mg po days1-21/D 40mg days 1,2,4,5,8,9,11,12q21x3 cyclesBortezomib+t+DB 1.3 mg/days 1,4,8,11,Q21x3 cyclesDouble
9、 ASCTMelphalan 200 mg/TD ConsolidationT 100mg po days 1-35/D320mg per cycle q35x2cyclesVTD ConsolidationB 1.3mg/days 1,8,1522q35/T 100mg po days1-35/D 320mg per cycleQ35,B x 2 cyclesMaintenanceDex9*t(4;14)del(17p)Br J Haematol,2008,140:625634.Mel 干细胞回输 G-CSFV V V V-6 -3 -2 0 +1 +4 +7V=万珂万珂 1.0-1.3mg
10、/m2 Mel=马法兰马法兰 200mg/m2 万珂万珂-马法兰用于马法兰用于ASCT预处理的研究预处理的研究缓解率缓解率CR=31%!，VGPR=46%CR+VGPR=77%（历史对照：常规历史对照：常规HDM预处理，预处理，ASCT后的后的CR+VGPR=4050%）Rousselet al.Hematology 2006;91(suppl.1),p98.EHA 2006,abs 0233#Overall and event-free survival are not improved by the use of myeloablative therapy following intens
11、ified chemotherapy in previously untreated patients with multiple myeloma:a prospective randomized phase 3 studyChristine M.Segeren,Pieter Sonneveld,Bronno van der Holt,et al.Erasmus Medical Center Rotterdam(Erasmus MC)and UniversityMedical Center Utrecht(UMCU)for the Dutch-Belgian Hemato-OncologyCo
12、operative Study Group(HOVON),The NetherlandsBLOOD,2003,101(6):2144-51TTPOSOverall SurvivalYearsProportion0246810120.0 0.2 0.4 0.6 0.8 1.0AllogeneicAutologous2yrs5 yrsAutologous74%33%Allogeneic51%39%p=0.006AutologousN=76AllogeneicN=42Relapse55(71%)19(45%)Infection6(8%)10(24%)GVHDNA3(7%)InterstitialPn
13、eumonitis4(5%)3(7%)VOD01(2%)MDS3(4%)0EBV LPD02(5%)Cardiac01(2%)Other8(10%)4(9%)Cumulative Incidence of Relapse YearsCumulative Incidence0246810120.00.20.40.60.81.0AutologousAllogeneicp=0.02High mortality with conventional allohas favored the Reduced Intensity Conditioning regimens(RIC)But the TRM is
14、 still 10%20%;cGVHD:35%70%&more relapses(extramedullary)to overcome relapses:“Tandem Auto-Allo”programAllogenic Hematopoietic Stem-cell Transplantation With Reduced-intensity Conditioning in Patients With Refractory and Recurrent Multiple MyelomaLong-Term Follow-UpAvichai Shimoni,Izhar Hardan,Franci
15、s Ayuk,Georgia Schilling,Djorde Atanackovic,Wolfgang Zeller,Ronit Yerushalmi,Axel Rolf Zander,Nicolaus Kroger,and Arnon NaglerDepartment of Bone Marrow Transplantation,Chaim Sheba Medical Center,Tel-Hashomer,IsraelDepartment of Bone Marrow Transplantation,University Hospital Hamburg,Hamburg,GermanyC
16、ancer,2010,epubosPFSA Comparison of Allografting with Autografting for Newly Diagnosed MyelomaBruno B,Rotta M,Patriarca F,et al.San Giovanni Battista HospitalUniversity of Turin tUniversity of Udine,UdineN Engl J Med 2007;356:1110-20.Mel100Pre DLI Maximal Response Current status9-persistent or 6 CR
17、5 CR-1 RelapseProgressive disease 3 PR 2 relapse3-CR -2 CR-1 relapsePrimary plasma cell leukemia and autologous stem cell transplantationhaematologica|2010;95(5):804-9Primary plasma cell leukemia(PCL):less than 5%of malignant PCD.It has a poor prognosis,median survival of 8-12 months.Autologous stem
18、 cell transplantation may improve survival.A retrospective analysis(European Group for Blood and Marrow Transplantation):272 patients PCL and 20844 with MM undergoing first autologous transplantation between 1980 and 2006.mSMART2.0:Classification of Active MM 3 years 5 years 7-10 yearsFISH Del 17P t
19、(14:16)t(14:20)GEP High risk signatureFISH t(4:14)Cytogenetic deletion 13 or hypodiploidPCLI3%All others including:Hyperdiploid t(11:14)t(6:14)High-Risk Intermediate-Risk Standard-RiskmSMART2.0:Treatment of Active MMHigh-Risk Intermediate-Risk Standard-RiskNovel approachesNew drugs”TT3 like”approach
20、for p53 deletion?Bortezomib based combinationHDM+/-consolidationLenalidomide maintenanceTargeted therapyRegimen whichprovides a high ORRand which minimizes early toxicity HDM could be delayed in patients achieving CRLenalidomide maintenance硼替佐米硼替佐米Vel+DexPADVCD雷利度胺雷利度胺RDRdRAD沙利度胺沙利度胺Thal+DexTADCTD常规
21、常规VADIDCY+DexVTDRVD干细胞采集干细胞采集高剂量的美法仑高剂量的美法仑干细胞回输干细胞回输CY=环磷酰胺；Rd=来那度胺+低剂量地塞米松；RD=雷利度胺+标准剂量地塞米松结结 论论1 造血干细胞移植是治疗造血干细胞移植是治疗MM有效手段之一；有效手段之一；2 移植优于单纯化疗；二次移植优于单次移植；移植优于单纯化疗；二次移植优于单次移植；3 诱导治疗中加入新药，大部分病人可能不需要诱导治疗中加入新药，大部分病人可能不需要二次移植；二次移植；4 清髓性移植有可能清除微小残留病；但移植相清髓性移植有可能清除微小残留病；但移植相关死亡率高；关死亡率高；5 NST可降低可降低TRM,但疗效有限；但疗效有限；6 移植后用新药维持治疗，可能提高疗效。移植后用新药维持治疗，可能提高疗效。
