AHS淋巴瘤干细胞移植

,自体造血干细胞移植治疗恶性淋巴瘤应用进展,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,Indications for Hematopoietic Stem Cell Transplants in the United States, 2010(Inflation factor: Auto=1.25 (80%), Allo=1.05 (95%), All Transplants),SUM12_28.ppt,Slide 8,Number of Transplants,1. HL,霍奇金淋巴瘤,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,HL :ASCT 综合治疗效果,复发/耐药 ： CR 34-80 % 长期生存率： 25- 50% 早期死亡率 ：421复发/耐药 ：10年生存率：50% 10y PFS： 45% 10y RFS： 23%首次复发：5年PFS 30 52%, 5年生存率： 3460,复发难治HL PET/CT结果与自体移植的疗效关系,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,Haematologica 2012,PET/CT -,PET/CT +,复发难治HD :不同预处理方案比较,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,1998-2009100 ptsBuMelTt(busulfan, melphalan,thiotepa): 60ptsOthers:40ptsCBV(21)TBICyE(14)BEAM(4)Melphalan(1)5 yr-OS 73% VS. 44%5 yr-PFS 66% VS. 37%No differences in toxicity and NRM,Improved outcome with busulfan, melphalan and thiotepa conditioning in AHSCT for relapsed/refractory HL,Tarunpreet B. Leukemia & Lymphoma, 2014; 55(3): 583587,PFS,OS,P=0.03,P=0.05,2. NHL, DLBCL弥漫大B淋巴瘤,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,复发NHL:自体移植是标准治疗手段 PARMA 随机对照研究,OS,PFS,美罗华治疗后复发：AHSCT价值， 2nd,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,Rituximab + DHAP and ASCT 复发DLBCL,Edo Vellenga et al, blood,2008 111: 537-543,DHAP112 73 40 19 9R-DHAP113 76 55 31 14,R-DHAP,DHAP,Cumulative percentage,Overall survival,CORAL研究： 移植后疗效 EFS,Failure from diagnosis = 12 months,Failure from diagnosis 12 months,Failure from diagnosis =70岁，移植相关死亡无差异OS预后因素：70岁，PS 2-4分，移植前未CRBiol Blood Marrow Transplant.2014 Jan 31.,100d: 4.1%1 yr: 5.9%2 yr: 7.7%3 yr: 10.7%,复发难治老年弥漫大B淋巴瘤DLBCL: A Nationwide Retrospective Study,Dai Chihara. Biol BMT. 20 (2014) 684-689,1993 to 2010 yearJapan Society for HCT database484 patients median age : 60 years,The cumulative risk of relapse 1-yr: 38.8% 2-yr: 45.5% 3-yr: 47.7%Multivariate analysis 70y PS 2 to 4 at ASCT not in remission at ASCT,High-Dose Chemotherapy with ASCT for Elderly Patients with Relapsed/Refractory DLBCL: A Nationwide Retrospective Study,Dai Chihara. Biol BMT. 20 (2014) 684-689,1-yr: 55.9%2-yr: 47.7%3-yr: 40.6%,1-yr: 69.7%2-yr: 57.9%3-yr: 49.6%,Dai Chihara. Biol BMT. 20 (2014) 684-689,High-Dose Chemotherapy with ASCT for Elderly Patients with Relapsed/Refractory DLBCL: A Nationwide Retrospective Study,High-Dose Chemotherapy with ASCT for Elderly Patients with Relapsed/Refractory DLBCL: A Nationwide Retrospective Study,2-yr OS 6064 64.6% 6569 50.6% 70y 45.7%,Dai Chihara. Biol BMT. 20 (2014) 684-689,Zevaline + BEAM: DLBCL 1st line,2011 lugano abs 256, GELA ,法国 75 DLBDL, R-CHOP/ R-ABVCP IPI 1 1;IPI 2 27; IPI 3-5 47 F/U 23m, 2y EFS 74%, 2y OS 80.5% PET +/- before AHSCT: same 1 toxic death promising with acceptable toxicity.,Zevalin +BEAM vs BEAM AHSCT for Aggressive Lymphoma,43 CD20+ pts 中位年龄55岁 病理类型 - DLBCL - transformed FL,Zevalin+BEAM N=22,BEAM N=21,R,AHSCT,Z-BEAM - Rituximab 250 mg/m2 - Zevalin 0.4 mCi/kg d -14 - Carmustine 300 mg/m2 d -6 - Etoposide 200 mg/m2 d -5 - -2 - Cytarabine 200 mg/m2 Q12h d -5 - -2 - Melphalan 140 mg/m2 d -1,Cancer.2012 Oct 1;118(19):4706-14,2y-OS:91% VS 62%(P=0.05),Zevalin +BEAM vs BEAM AHSCT for Aggressive Lymphoma,2y-PFS: 59% VS 37%(P=0.2),Cancer.2012 Oct 1;118(19):4706-14,23 ptswithout CR to salvage chemotherapy6 pts RIT combined with HD-chemotherapy8 pts received a sequential HD- chemotherapy with a second ASCT,Myeloablative Anti-CD20 RIT High-Dose Chemotherapy Followed by ASCT for Relapsed/Refractory B-Cell Lymphoma Results in Excellent Long-Term Survival,Wagner JY. Oncotarget, June, Vol.4, No 6,The ORR 87% CR: 64%Median PFS 47.5mMedian OS 101.5 months,Myeloablative Anti-CD20 RIT High-Dose Chemotherapy Followed by ASCT for Relapsed/Refractory B-Cell Lymphoma Results in Excellent Long-Term Survival,Wagner JY. Oncotarget, June, Vol.4, No 6,(A) OS according to treatment modality(B) PFS according to treatment modality,(C) OS RIT VS. RIT/HD-CTX or RIT/BEAM (D) PFS RIT VS. RIT/HD-CTX or RIT/BEAM,Myeloablative Anti-CD20 RIT High-Dose Chemotherapy Followed by ASCT for Relapsed/Refractory B-Cell Lymphoma Results in Excellent Long-Term Survival,Wagner JY. Oncotarget, June, Vol.4, No 6,Philippe A. J Clin Oncol 31:4199-4206.,PD-1 Blockade Pidilizumab + AHSCT DLBCL an International Phase II Trial,66例30 centers in USA化疗敏感复发 ，Chemotherapy sensitive,66pts,Pidilizumab(PD-1) 1.5 mg/kg3, Q42d 30 to 90d from AHSCT,AHSCT,Restagedat 30, 44, and 69 w,OS (16m): 85%PFS(16m): 72%,Disabling Immune Tolerance by PD-1 Blockade With Pidilizumab After AHSCT for DLBCL:Results of an International Phase II Trial,PFS and OS of all eligible patients,PFS and OS of the 24 eligible patients who PET(+) after salvage therapy,PFS(16m): 70%(PET+) 72%(PET-),Philippe A. J Clin Oncol 31:4199-4206.,3. PTCL-U 外周非特异性,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,复发耐药T-NHL长期随访结果，常规化疗,N=45, 总生存曲线,黄慧强等，2007 癌症,ASCT 治疗外周T淋巴瘤：一线,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,ASCT 外周T淋巴瘤：复发,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,T-NHL自体干细胞移植随访结果,35 例,中位随访23个月，预计中位总生存54个月，PTCL-U 17.1%，LBL 42.9%，ALCL20%，NK/T 14.33%，皮下脂膜炎样T 5.7%1，3，5年OS为71%，59%，46%,中山大学肿瘤医院内科,ASHCT 治疗T-NHL(一线/复发),2011 lugano ICML, abs 100 MDACC 美国126例， 49（18-75），初治33， 预处理：BEAM 4年 OS PFS CR1 87 67 敏感复发 39 36 难治 24 15 PTCLU 42 48 ALCL 47 37 NK/T 6 67 LBL 14 AHSCT 考虑一线应用,AutoHSCT vs alloHSCT T-NHL: CIBMTR analysis (19962006),自体，autoHCT (n=115) more in ALCL (53% vs. 40%, p=0.04) less advanced: CR1(35% vs. 14%, p=0.001),chemosensitive disease (86% vs. 60%, p0.0001)2 lines prior therapy (65% vs. 44%, p0.001)异基因，alloHCT (n=126, 76 matched siblings),100 d TRM 1yr OS 3yr OS 复发死亡 autoHCT 2% 62% 53% 73% alloHCT 17% 52% 41% 44%,Sonali Smith,et al. ASH2010, Abstract 689.,Hematopoietic Cell Transplantation for Systemic MatureT-Cell Non-Hodgkin Lymphoma,NRM :non relapse mortality,Sonali M. J Clin Oncol 31:3100-3109.,241pts - ALCL (112) - PTCL-U(102) - AITL(27) 60 yr Lines prior to transplantation - 3(164) - 3(73),autoHCT N=115,Primary outcomesPFSNRMOS,alloHCT N=126,OS,PFS,NRM,NRM,PFS,OS,Sonali M. J Clin Oncol 31:3100-3109.,Hematopoietic Cell Transplantation for Systemic MatureT-Cell Non-Hodgkin Lymphoma,PFS,OS,NRM,PFS,OS,Hematopoietic Cell Transplantation for Systemic MatureT-Cell Non-Hodgkin Lymphoma,Sonali M. J Clin Oncol 31:3100-3109.,P Corradini. Leukemia (2014), 17,Intensified chemo-immunotherapy SCT in newly diagnosed PTCL,AL: alemtuzumab HyperCHidam: - HD-MTX 1.6 g/m2 d1, - CTX 300 mg/m2 Q12h d1-3 - HD-Ara-C 2 g/m2 Q12h d1-3,P Corradini. Leukemia (2014), 17,Clin A study - 4 yr OS 49% - 4 yr PFS 44% - 4 yr DFS 65%,Intensified chemo-immunotherapy SCT in newly diagnosed PTCL,P Corradini. Leukemia (2014), 17,Clin B study - 4 yr OS 32% - 4 yr PFS 26% - 4 yr DFS 44%,Intensified chemo-immunotherapy SCT in newly diagnosed PTCL,晚期、复发NK/T 淋巴瘤,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,，自体外周血造血干细胞移植: NKT淋巴瘤，1st,获益患者CR、III-IV期预后不良,（kim HJ,et al. Bone Marrow Transplant. 2006),自体移植: III/IV 期和复发难治 NK/T Promising,3-y OS 78.6%13.9%3-y PFS 63.6% 14.5%,Huang hui-qiang, et al in press,中山大学肿瘤医院 SYSUCC,P-Gemox CR/PR自体移植,YDM, 女，24岁，IVB NK/T,腹部巨大肿块，PS=2 腹腔肠道广泛受累 1疗程后肠穿孔，人工肛， PEG-Gemox 6疗程，CR ASCT 后12个月 CCR,Upfront Autologuos Stem-Cell Transplantation in Peripheral T-Cell Lymphoma: NLG-T-01,5y-OS 51%,5y-PFS 41%,J Clin Oncol.2013 May 1;31(13):1624-30.,4 . FL， 滤泡型淋巴瘤,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,Randomized Trials of Upfront Autologous Transplantation for FL,1. Gyan E, et al. Blood. 2009;113:995-1001. 2. Lenz G, et al. Blood. 2004;104:2667-2674. 3. Sebban C, et al. Blood. 2006;108:2540-2544. 4. Ladetto M, et al. Blood. 2008;111:4004-4013.,Long term outcome of AHSCT 复发滤泡型,248 pts, age 47 (20-67) yMedian prior chemotherapies 2, 110 pts AHSCT onlyMedian F/U 6 years ( 1-16 ) y47% progression13% died without NHL44% 5Y EFS 63% 5y OS2005 ASCO ,abstract 6567J Vose et al University of Nebraska medical center,CUP trial: PFS,1.00.80.60.40.20,012 24 36 48 60 72 84,Months,Proportion progression-free,EventsTotalChemotherapy2024Unpurged 922Purged1124,Schouten H, et al. J Clin Oncol 2003;21:391827,Tandem Transplant for，双移植 Follicular NHL 3 线随访39 月, OS 96%3年PFS 96%,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,5 .套细胞淋巴瘤MCL,1.套细胞淋巴瘤2008，2009R-CHOP + AHSCT : R-CHOP+ IFN,PFS R-CHOP + AHSCT VS IFN,PFS， R-CHOP + AHSCT VS 其他,年轻一线：MCL1 vs MCL 2,套细胞淋巴瘤长期随访：MCL2方案,360 例患者2000-2009年18岁 Multivariate analysis,一项EBMT关于套细胞淋巴瘤移植后复发的预后因素和生存研究的回顾性分析,S. Dietrich. Annals of Oncology25: 10531058, 2014,Median OS: 19m,Relapesd 12m,S. Dietrich. Annals of Oncology25: 10531058, 2014,一项EBMT关于套细胞淋巴瘤移植后复发的预后因素和生存研究的回顾性分析,First line vs. salvage SCT,OS after ASCT failure by timing of first ASCT,OS after ASCT failure by refractory disease,Sensitive vs. refractory,S. Dietrich. Annals of Oncology25: 10531058, 2014,一项EBMT关于套细胞淋巴瘤移植后复发的预后因素和生存研究的回顾性分析,2000-2003年 vs.2004-2007年,OS after ASCT failure by calendar yearof relapse,OS from 3 months landmark after ASCT failure by response to first-salvage regimen given for relapse,CR vs.PR vs. SD/PD,S. Dietrich. Annals of Oncology25: 10531058, 2014,一项EBMT关于套细胞淋巴瘤移植后复发的预后因素和生存研究的回顾性分析,Nordic MCL3 研究:90Y-ibritumomab-tiuxetanadded 联合BEAM/C 治疗移植前未CR的套细胞淋巴瘤,Arne K. Blood. 2014 123: 2953-2959,160pts Untreated Stage II-IV 66 yr,MCL2 6 R-maxi-CHOP R-HD-Ara-C,RESP O NDING,CR,CRu/PR Zevalin1 1w before ASCT Rituximab 250mg/m2 1 w before and just prior to Zevalin,AHSCT BEAM/BEAC,EFS OS PFS,Survival curves for MCL2 and MCL3,Nordic MCL3 研究:90Y-ibritumomab-tiuxetanadded 联合BEAM/C 治疗移植前未CR的套细胞淋巴瘤,Arne K. Blood. 2014 123: 2953-2959,移植前基于PET/CT扫描结果的生存曲线,PFS,OS,Nordic MCL3 研究:90Y-ibritumomab-tiuxetanadded 联合BEAM/C 治疗移植前未CR的套细胞淋巴瘤,Arne K. Blood. 2014 123: 2953-2959,基于微小病灶残留检测的PFS曲线,移植前,移植后,Nordic MCL3 研究:90Y-ibritumomab-tiuxetanadded 联合BEAM/C 治疗移植前未CR的套细胞淋巴瘤,Arne K. Blood. 2014 123: 2953-2959,移植前获得CR和Cru/PR患者的DOR曲线,Arne K. Blood. 2014 123: 2953-2959,Nordic MCL3 研究:90Y-ibritumomab-tiuxetanadded 联合BEAM/C 治疗移植前未CR的套细胞淋巴瘤,6. Allo-HSCT 和其他,Improved supportive therapy and outcome after auto vs. alloHSCT?,Allogeneic SCT over time,Autologous SCT over time,But:- retrospective study with heterogenous patient population- TBI conditioning regimen significantly lower relapse rate (p=0.02