多发性骨髓瘤的造血干细胞移植课件.ppt
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1、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,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多发性骨髓瘤的造血干细胞移植,为什么要移植?,多发性骨髓瘤的造血干细胞移植,为什么要移植?多发性骨髓瘤的造血干细胞移植,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,多发性骨髓瘤的造血干细胞移植,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Bre,P10 -5 P=0.07,EFS CR vs nCR or PR nCR vs PR,OS CR vs nC
2、R CR vs PR nCR vs PR,P=0.01 P10 -6 P=0.04,Lahuerta et al. JCO 2008;26:5775-5782,缓解程度与长生存密切相关,无事件生存率%,总生存率%,多发性骨髓瘤的造血干细胞移植,P10 -5 EFS OS P=0.01,Barlogie B, et al. Cancer. 2008;113:355359. .,持久CR是长生存的最重要因素,0 1 2 3 4 5 6,SUS-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%,Barlog
3、ie B, et al. Cancer. 2008;113:355359. .,P-value: a vs b0.0001, b vs c 0.0001, a vs c 0.0001,a,b,c,多发性骨髓瘤的造血干细胞移植,Barlogie B, et al. Cancer. 200,以新药为基础的诱导方案的疗效,诱导方案,多发性骨髓瘤的造血干细胞移植,以新药为基础的诱导方案的疗效诱导方案多发性骨髓瘤的造血干细胞,ASCT能进一步提高新药诱导后的疗效,*Post-transplant data not available,Harousseau et al. ASH/ASCO symposiu
4、m during ASH 2008Rajkumar et al. ASCO 2008 (Abstract 8504); ASH 2008 (joint ASH/ASCO symposium),Lokhorst et al. Haematologica 2008;93:124127Sonneveld et al. ASH 2008 (Abstract 653); IMW (Abstract 152) Cavo et al. ASH 2008 (Abstract 158); IMW 2009 (Abstract 451),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,多发性骨
5、髓瘤的造血干细胞移植,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,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,多发性骨髓瘤的造血干细胞移植,以硼替佐米为基础的诱导方案,*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:ab
6、stract 152.,多发性骨髓瘤的造血干细胞移植,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。,多发性骨髓瘤的造血干细胞移植,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。,多发性骨髓瘤的造血干细胞移植,病人的年龄多限定在65
7、岁以下,但也有超出该年龄病人的报道。多,Kumar et al ASH2009 (Abstr 956),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?,VRD3,Stem Collection,ASCT,VRD2,R12m,多发性骨髓瘤的造血干细胞移植,Kumar et al ASH2009 (Abstr 956,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,多发性骨髓瘤的造血干细胞移植,小结患者的生存与缓解程度有关多发性骨髓瘤的造血干细胞移植,干细胞动员的
8、问题,多发性骨髓瘤的造血干细胞移植,干细胞动员的问题多发性骨髓瘤的造血干细胞移植,High 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 Haematolog
9、y Hammersmith Hospital Imperial College Healthcare NHS Trust, London, UK,Bone Marrow Transplantation (2010), 14,epub,多发性骨髓瘤的造血干细胞移植,High rate of stem cell mobiliz,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,Figure 1 Induction therapy with CY and thalidomide with dexamethasone (CTD) impairs the stem cell collectio
10、n 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.,多发性骨髓瘤的造血干细胞移植,Figure 1 Inducti
11、on therapy wit,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,预 处 理,多发性骨髓瘤的造血干细胞移植,预 处 理多发性骨髓瘤的造血干细胞移植,How to improve the efficacy of condition regimens,Melphalan 200mg/m2.the gold standardMelphalan+Busulphan.may be superiorMelphalan+Bortezomib70%VGPR(35%CR) (1mg/m2 D-6 -3 +1 +4)Melphalan+Bortezomib53%VGPR (1.3mg/m2
12、 D-1 or +1),多发性骨髓瘤的造血干细胞移植,How to improve the efficacy of,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 Insti
13、tute, Hershey, PA, USA,Bone Marrow Transplantation (2009) 44, 157161,多发性骨髓瘤的造血干细胞移植,BU and CY as conditioning regi,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,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
14、.,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
15、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.
16、,多发性骨髓瘤的造血干细胞移植,Figure 1 OS of multiple myelom,移植后的巩固与维持治疗,多发性骨髓瘤的造血干细胞移植,移植后的巩固与维持治疗多发性骨髓瘤的造血干细胞移植,2009 ASH Abstract 351,A Phase Study of Double Autotransplantation Incorporating Bortezomib- Thalidomide- Dexamethasone (VTD) or Thalidomide- Dexamethasone (TD) for Multiple Myeloma: Superior Clinical
17、Outcomes with VTD Compared to TDMichele Cabvo, Paola Tacchetti, Francesca Patriarca, et al.sergnoli Institute of Hematology, Bologna University School of Medicine, Bologna, ItalyItalian Myeloma Network GIMEMA, Italy,多发性骨髓瘤的造血干细胞移植,2009 ASH Abstract 351A Phase ,Study Design,.,REGISTRATION,Thalidomide
18、 +DexT 100-200 mg po days1-21/D 40mg days 1,2,4,5,8,9,11,12q21x3 cycles,Bortezomib + t + DB 1.3 mg/ days 1,4,8,11,Q21x3 cycles,Double ASCTMelphalan 200 mg/,TD ConsolidationT 100mg po days 1-35/D320mg per cycle q35x2cycles,VTD ConsolidationB 1.3mg/ days 1,8,1522q35/T 100mg po days1-35/D 320mg per cyc
19、leQ35, B x 2 cycles,MaintenanceDex,多发性骨髓瘤的造血干细胞移植,Study Design.REGISTRATIONThali,Patient Characteristics,.,9,多发性骨髓瘤的造血干细胞移植,Patient Characteristics.VTD(n=,Best Response,.,多发性骨髓瘤的造血干细胞移植,Best Response.VTD(%)TD(%)PCR57,PFS in High-risk Cytogenetics*,*t (4;14) del (17p),多发性骨髓瘤的造血干细胞移植,PFS in High-risk
20、Cytogenetics*,Br J Haematol,2008,140:625634.,多发性骨髓瘤的造血干细胞移植,Br J Haematol,2008,140:625634,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,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,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,Mel 干细胞回输 G-CSFV V V V,-6 -3 -2 0 +1 +4 +7,V= 万珂 1.0-1.3mg/m2 Mel = 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 =
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