多发性骨髓瘤的造血干细胞移植PPT学习教案

1、会计学1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第1页/共76页Brenner et al;Blood 2008;111:2521-2526第2页/共76页无无事事件件生生存存率率%总总生生存存率率%第3页/共76页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 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

2、22.5%。1.Harousseau JL, et al. JCO 2010 in press. 2. Sonneveld P, et al. IMW 2009:abstract 152.第9页/共76页第10页/共76页第11页/共76页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 CollectionASCTVRD2R12m第12页/共76页第13页/共76页第14页/共76页High

3、rate of stem cell mobilization failure after thalidomide and oral cyclophosphamide induction therapy for multiple myelomaHW 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 Health

4、care NHS Trust, London, UKBone Marrow Transplantation (2010), 14,epub第15页/共76页第16页/共76页Figure 1 Induction therapy with CY and thalidomide with dexamethasone (CTD) impairs the stem cell collection yield and increases the number of apheresis procedures required. (a) Bars show the median number of CD34

5、tcells/kg collected overall, on the first apheresis day, and per apheresis procedure. (b) Bars show the percentage of patients undergoing X2 apheresis procedures.第17页/共76页第18页/共76页第19页/共76页第20页/共76页BU and CY as conditioning regimen for autologous transplant in patientswith multiple myelomaG Talamo,

6、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, 157161第21页/共76页第22页/共76页Figure 1 OS of multiple myeloma patients treated with the BU/CY regimen and

7、 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 intervalFigure 3 PFS of multiple myeloma patients treated with oral (n1

8、3, continuous line) vs . 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 out as salvage therapy, that is, on disease progression/relapse

9、 (n17, dotted line). Survival is calculated from the time of MM diagnosis.第23页/共76页移植后的巩固与维持治疗移植后的巩固与维持治疗第24页/共76页第25页/共76页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 ASCTMelphalan 200 mg/T

10、D 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 cyclesMaintenanceDex第26页/共76页9第27页/共76页第28页/共76页*t (4;14) del (17p)第29页/共76页Br J Haematol,2008,140:625634.第30页/共76页第31页/共76页第32页/共76页第33页/共76页 Me

11、l 干细胞回输 G-CSFV V V V-6 -3 -2 0 +1 +4 +7V= 万珂万珂 2 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#第34页/共76页第35页/共76页第36页/共76页第37页/共76页Overall

12、and event-free survival are not improved by the use of myeloablative therapy following intensified 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 Rott

13、erdam (Erasmus MC) and UniversityMedical Center Utrecht (UMCU) for the Dutch-Belgian Hemato-OncologyCooperative Study Group (HOVON), The NetherlandsBLOOD, 2003 , 101( 6):2144-51第38页/共76页第39页/共76页第40页/共76页TTPOS第41页/共76页第42页/共76页第43页/共76页第44页/共76页Overall SurvivalYearsProportion024681012AllogeneicAutol

14、ogous2yrs5 yrsAutologous74%33%Allogeneic51%39%第45页/共76页AutologousN=76AllogeneicN=42Relapse55 (71%)19 (45%)Infection6 (8%)10 (24%)GVHDNA3 (7%)InterstitialPneumonitis4 (5%)3(7%)VOD01 (2%)MDS3 (4%)0EBV LPD02 (5%)Cardiac01 (2%)Other8 (10%)4 (9%)第46页/共76页Cumulative Incidence of Relapse YearsCumulative In

15、cidence024681012AutologousAllogeneic第47页/共76页High mortality with conventional allohas favored the Reduced Intensity Conditioning regimens (RIC) But the TRM is still 10%20%; cGVHD: 35%70% & more relapses (extramedullary) to overcome relapses: “Tandem Auto-Allo” program第48页/共76页第49页/共76页Allogenic

16、Hematopoietic Stem-cell Transplantation With Reduced-intensity Conditioning in Patients With Refractory and Recurrent Multiple MyelomaLong-Term Follow-UpAvichai Shimoni, Izhar Hardan, Francis Ayuk, Georgia Schilling, Djorde Atanackovic, Wolfgang Zeller, Ronit Yerushalmi, Axel Rolf Zander, Nicolaus K

17、roger, and Arnon NaglerDepartment of Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, IsraelDepartment of Bone Marrow Transplantation,University Hospital Hamburg, Hamburg, GermanyCancer,2010,epub第50页/共76页osPFS第51页/共76页第52页/共76页第53页/共76页第54页/共76页A Comparison of Allografting with

18、 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.第55页/共76页第56页/共76页第57页/共76页第58页/共76页第59页/共76页第60页/共76页第61页/共76页第62页/共76页第63页/共76页第64页/共76页Pre DLI Maximal Response

19、Current status9-persistent or 6 CR 5 CR-1 RelapseProgressive disease 3 PR 2 relapse3-CR - 2 CR-1 relapse第65页/共76页第66页/共76页Primary 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 p

20、oor prognosis, median survival of 8-12 months. Autologous stem 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. 第67页/共76页第68页/

21、共76页第69页/共76页第70页/共76页第71页/共76页mSMART2.0: Classification of Active MM 3 years 5 years 7-10 yearsFISH Del 17P t(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-Risk第72页/共76页mSMART2.0: Treatment of Active MMHigh-Risk Intermediate-Risk Standard-RiskNovel appr