多发性骨髓瘤移植首都医科大学附属北京朝阳医院精品课件陈文明

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 陈文明陈文明 首都医科大学附属北京朝阳医院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北京市多发性骨髓瘤医疗研究中心 为什么要移植？ 不同时间段内多发性骨髓瘤 主要年龄组患者的10年生存率 Brenner et al;Blood 2008;111:2521-2526 PVGPR 38 vs 15*33 vs 12* PR 78.5 vs 63*80 vs 64* ASCT后反应应，% CR16 vs 9*15 vs 4* VGPR 54 vs 37*59 vs 47* PR 80 vs 7792 vs 77* *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.Harousseau JL, et al. JCO 2010 in press. 2. Sonneveld P, et al. IMW 2009:abstract 152. n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。 n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。 n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。 Kumar et al ASH2009 (Abstr 956） VRD5 Stem Collection R12m ASCT at relapse VRD3 复发前和复发后进行ASCT疗效相同 IFM-DFCL2009 ASCT 在复发前还是在复发后进行？ nVRD3 Stem Collection ASCT VRD2 R12m 小结 n患者的生存与缓解程度有关 n化疗可以提高缓解率及缓解程度 n二次移植优于单次移植 n新药的应用可以进一步提高疗效 n早期与晚期移植的疗效相似 干细胞动员的问题 High rate of stem cell mobilization failure after thalidomide and oral cyclophosphamide induction therapy for multiple myeloma HW Auner, L Mazzarella, L Cook, R Szydlo, F Saltarelli, J Pavlu, M Bua, C Giles, JF Apperley and A Rahemtulla Department of Haematology Hammersmith Hospital Imperial College Healthcare NHS Trust, London, UK Bone Marrow Transplantation (2010), 14,epub 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 CD34tcells/kg collected overall, on the first apheresis day, and per apheresis procedure. (b) Bars show the percentage of patients undergoing X2 apheresis procedures. 预 处 理 How to improve the efficacy of condition regimens nMelphalan 200mg/m2the gold standard nMelphalan+Busulphan.may be superior nMelphalan+Bortezomib70%VGPR(35%CR) (1mg/m2 D-6 -3 +1 +4) nMelphalan+Bortezomib53%VGPR (1.3mg/m2 D-1 or +1) BU and CY as conditioning regimen for autologous transplant in patients with multiple myeloma G Talamo, DF Claxton, DW Dougherty, CW Ehmann, J Sivik, JJ Drabick and W Rybka Bone Marrow Transplant Program, Penn State Milton S Hershey Cancer Institute, Hershey, PA, USA Bone Marrow Transplantation (2009) 44, 157161 Figure 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 interval Figure 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 out 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 2009 ASH Abstract 351 A Phase Study of Double Autotransplantation Incorporating Bortezomib- Thalidomide- Dexamethasone (VTD) or Thalidomide- Dexamethasone (TD) for Multiple Myeloma: Superior Clinical Outcomes with VTD Compared to TD Michele Cabvo, Paola Tacchetti, Francesca Patriarca, et al. sergnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy Italian Myeloma Network GIMEMA, Italy Study Design . REGISTRATION Thalidomide +Dex T 100-200 mg po days 1-21/D 40mg days 1,2,4, 5,8,9,11,12q21x3 cycles Bortezomib + t + D B 1.3 mg/ days 1,4,8,11, Q21x3 cycles Double ASCT Melphalan 200 mg/ TD Consolidation T 100mg po days 1-35/D 320mg per cycle q35x2 cycles VTD Consolidation B 1.3mg/ days 1,8,15 22q35/T 100mg po days 1-35/D 320mg per cycle Q35, B x 2 cycles Maintenance Dex Patient Characteristics . VTD(n=241)TD(n=239) Age (years)56.336.8855.867.41 Stage ISS(%) + 107(44) 134(56) 107(45) 132(55) 2-MG (mg/L)3.812.483.832.14 Albumin (g/dL)3.830.644.173.97 Creatinine (mg/dL)1.010.301.010.31 Hb (g/dL)11.101.9111.241.96 Plts (X10 /L)243.6989.06235.8678.04 BMPC meanSD(%)52.4223.1952.7824.15 Genetic abnormalities(by FISH in 93% of pts) Del(13q) pos (%) del(13q) alone t(4:14) pos (%) del (17p) pos (%) 4730 18 7 4626 20 8 9 Best Response . VTD(%)TD(%)P CR57.2031.070.0001 CR+ nCR 69.9151.23 20%40% Age cGVHD: 35%70% 356:1110-20. Non-myeloablative Transplantation AuthorConditioning regimen GVHD regimenN (URD) Prior Auto TRM % CR % Gr 2-4 aGVHD % Chronic GVHD % OS % (yrs) KrogerMel100/Flu/ATGCSA/MTX17 (8(2) 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- Simon Mel/FluCSA/MTX29 (NR)102128415160 (2) Auto-allo RIC vs Tandem Auto n3 studies(IFM, PETHEMA, HOVON)No benefit n2 studies(GIMEMA, EBMT)significant benefit (EFS, OS) #Differences in patients characteristics, GVHD prophylaxis, 95(5):804-9 Primary plasma cell leukemia(PCL): less than 5% of malignant PCD. It has a poor 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. mSMART2.0: Classification of Active MM 3 years 5 years 7-10 years FISH Del 17P t(14:16) t(14:20) GEP High risk signature FISH t(4:14) Cytogenetic deletion 13 or hypodiploid PCLI3% All others including: Hyperdiploid t(11:14) t(6:14) High-Risk Intermediate-Risk Standard-Risk mSMART2.0: Trea