AHS-淋巴瘤干细胞移植课件

1、自体造血干细胞移植治疗恶性淋巴瘤应用进展AHS 淋巴瘤干细胞移植AHS 淋巴瘤干细胞移植AHS 淋巴瘤干细胞移植AHS 淋巴瘤干细胞移植AHS 淋巴瘤干细胞移植AHS 淋巴瘤干细胞移植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.pptSlide 8Number of TransplantsAHS 淋巴瘤干细胞移植Indicatio

2、ns for Hematopoietic 1. HL,霍奇金淋巴瘤AHS 淋巴瘤干细胞移植中山大学肿瘤医院2022/10/22022/10/21. HL,霍奇金淋巴瘤AHS 淋巴瘤干细胞移植中山大学肿瘤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： 3460AHS 淋巴瘤干细胞移植HL :ASCT 综合治疗效果复发/耐药 ： AHS 淋巴瘤复发难治HL PET/CT结果与自体移植的疗效关系

3、Haematologica 2012 PET/CT - PET/CT + AHS 淋巴瘤干细胞移植中山大学肿瘤医院2022/10/22022/10/2复发难治HL PET/CT结果与自体移植的疗效关系Haem复发难治HD :不同预处理方案比较AHS 淋巴瘤干细胞移植中山大学肿瘤医院2022/10/22022/10/2复发难治HD :不同预处理方案比较AHS 淋巴瘤干细胞移植中1998-2009100 ptsBuMelTt(busulfan, melphalan,thiotepa): 60ptsOthers:40ptsCBV(21)TBICyE(14)BEAM(4)Melphalan(1)5 y

4、r-OS 73% VS. 44%5 yr-PFS 66% VS. 37%No differences in toxicity and NRMImproved outcome with busulfan, melphalan and thiotepa conditioning in AHSCT for relapsed/refractory HLTarunpreet B. Leukemia & Lymphoma, 2014; 55(3): 583587PFSOSP=0.03P=0.05AHS 淋巴瘤干细胞移植1998-2009Improved outcome with2. NHL, DLBCL弥

5、漫大B淋巴瘤AHS 淋巴瘤干细胞移植中山大学肿瘤医院2022/10/22022/10/22. NHL, DLBCL弥漫大B淋巴瘤AHS 淋巴瘤干细复发NHL:自体移植是标准治疗手段 PARMA 随机对照研究OSPFSAHS 淋巴瘤干细胞移植复发NHL:自体移植是标准治疗手段 PARMA 随机对照研美罗华治疗后复发：AHSCT价值， 2ndAHS 淋巴瘤干细胞移植中山大学肿瘤医院2022/10/22022/10/2美罗华治疗后复发：AHSCT价值， 2ndAHS 淋巴瘤干Rituximab + DHAP and ASCT 复发DLBCLEdo Vellenga et al, blood,2008

6、 111: 537-543DHAP112 73 40 19 9R-DHAP113 76 55 31 14R-DHAPDHAPCumulative percentageOverall survivalAHS 淋巴瘤干细胞移植Rituximab + DHAP and ASCT 复发DCORAL研究： 移植后疗效 EFSFailure from diagnosis = 12 monthsFailure from diagnosis 12 monthsFailure 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 Mar

7、row Transplant.2014 Jan 31.AHS 淋巴瘤干细胞移植AHSCT：复发难治老年DLBCL-日本血液学协会回顾性研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 StudyDai Chihara. Biol BMT. 20 (2014) 684-6891993 to 2010 yearJapan Society for HCT database484 patients median age : 60 yearsAHS 淋巴瘤干细胞移植100d:

8、4.1%复发难治老年弥漫大B淋巴瘤DLBCL: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 ASCTHigh-Dose Chemotherapy with ASCT for Elderly Patients with Relapsed/Refractory DLBCL: A Nationwide Retrospective StudyDai Chihara. Biol BMT. 20

9、 (2014) 684-689AHS 淋巴瘤干细胞移植The cumulative risk of relapse1-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) 684-689High-Dose Chemotherapy with ASCT for Elderly Patients with Relapsed/Refractory DLBCL: A Nationwide Retrospective StudyAHS 淋巴瘤干细胞移植1-yr: 5

10、5.9%1-yr: 69.7%Dai ChihHigh-Dose Chemotherapy with ASCT for Elderly Patients with Relapsed/Refractory DLBCL: A Nationwide Retrospective Study2-yr OS 6064 64.6% 6569 50.6% 70y 45.7%Dai Chihara. Biol BMT. 20 (2014) 684-689AHS 淋巴瘤干细胞移植High-Dose Chemotherapy with ASZevaline + BEAM: DLBCL 1st line 2011 l

11、ugano 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.AHS 淋巴瘤干细胞移植Zevaline + BEAM: DLBCL 1st linZevalin +BEAM vs BEAM AHSCT for Aggressive Lymphoma 43 CD20+ pts 中位年龄5

12、5岁 病理类型 - DLBCL - transformed FLZevalin+BEAM N=22BEAM N=21RAHSCTZ-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 -1Cancer.2012 Oct 1;118(19):4706-14AHS 淋巴瘤干细胞移植Zevalin +BE

13、AM vs BEAM AHSCT f2y-OS:91% VS 62%(P=0.05)Zevalin +BEAM vs BEAM AHSCT for Aggressive Lymphoma2y-PFS: 59% VS 37%(P=0.2)Cancer.2012 Oct 1;118(19):4706-14AHS 淋巴瘤干细胞移植2y-OS:91% VS 62%(P=0.05)Zevali23 ptswithout CR to salvage chemotherapy6 pts RIT combined with HD-chemotherapy8 pts received a sequential

14、HD- chemotherapy with a second ASCTMyeloablative Anti-CD20 RIT High-Dose Chemotherapy Followed by ASCT for Relapsed/Refractory B-Cell Lymphoma Results in Excellent Long-Term SurvivalWagner JY. Oncotarget, June, Vol.4, No 6AHS 淋巴瘤干细胞移植23 ptsMyeloablative Anti-CD20 The ORR 87% CR: 64%Median PFS 47.5mM

15、edian OS 101.5 monthsMyeloablative Anti-CD20 RIT High-Dose Chemotherapy Followed by ASCT for Relapsed/Refractory B-Cell Lymphoma Results in Excellent Long-Term SurvivalWagner JY. Oncotarget, June, Vol.4, No 6AHS 淋巴瘤干细胞移植Myeloablative Anti-CD20 RIT H(A) OS according to treatment modality(B) PFS accor

16、ding 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 SurvivalWagner JY. Oncotarget, June, Vol.4, No 6AHS 淋巴瘤干细胞

17、移植(A) OS according to treatment Philippe A. J Clin Oncol 31:4199-4206. PD-1 Blockade Pidilizumab + AHSCT DLBCL an International Phase II Trial66例30 centers in USA化疗敏感复发 ，Chemotherapy sensitive66pts Pidilizumab(PD-1) 1.5 mg/kg3, Q42d 30 to 90d from AHSCTAHSCTRestagedat 30, 44, and 69 wAHS 淋巴瘤干细胞移植Phi

18、lippe A. J Clin Oncol 31:41OS (16m): 85%PFS(16m): 72%Disabling Immune Tolerance by PD-1 Blockade With Pidilizumab After AHSCT for DLBCL:Results of an International Phase II TrialPFS and OS of all eligible patientsPFS and OS of the 24 eligible patients who PET(+) after salvage therapyPFS(16m): 70%(PE

19、T+) 72%(PET-)Philippe A. J Clin Oncol 31:4199-4206.AHS 淋巴瘤干细胞移植OS (16m): 85%Disabling Immune3. PTCL-U 外周非特异性AHS 淋巴瘤干细胞移植中山大学肿瘤医院2022/10/22022/10/23. PTCL-U 外周非特异性AHS 淋巴瘤干细胞移植中复发耐药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AHS 淋巴瘤干细胞移植复发耐药T-NHL长期随访结果，常规化疗 ASCT 治疗外周T淋巴瘤：一线AHS 淋巴瘤干细胞移植中山大学肿瘤医院2022/10/2202

20、2/10/2ASCT 治疗外周T淋巴瘤：一线AHS 淋巴瘤干细胞移植中山ASCT 外周T淋巴瘤：复发AHS 淋巴瘤干细胞移植中山大学肿瘤医院2022/10/22022/10/2ASCT 外周T淋巴瘤：复发AHS 淋巴瘤干细胞移植中山大学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AHS 淋巴瘤干细胞移植T-NHL自体干细胞移植随访结果35 例,中山大学肿瘤医院内ASHCT 治疗T-NHL

21、(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 AHS 淋巴瘤干细胞移植ASHCT 治疗T-NHL(一线/复发) 2011 lugaAutoHSCT vs alloHSCT T-NHL: CIBMTR analysis (19962006)自体，autoHCT (n=115) more in ALCL (53% v

22、s. 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 6

23、89. AHS 淋巴瘤干细胞移植AutoHSCT vs alloHSCT T-NHL:Hematopoietic Cell Transplantation for Systemic MatureT-Cell Non-Hodgkin LymphomaNRM :non relapse mortalitySonali 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=115P

24、rimary outcomesPFSNRMOS alloHCT N=126AHS 淋巴瘤干细胞移植Hematopoietic Cell TransplantaOSPFSNRMNRMPFSOSSonali M. J Clin Oncol 31:3100-3109.Hematopoietic Cell Transplantation for Systemic MatureT-Cell Non-Hodgkin LymphomaAHS 淋巴瘤干细胞移植OSPFSNRMNRMPFSOSSonali M. J ClPFSOSNRMPFSOSHematopoietic Cell Transplantatio

25、n for Systemic MatureT-Cell Non-Hodgkin LymphomaSonali M. J Clin Oncol 31:3100-3109.AHS 淋巴瘤干细胞移植PFSOSNRMPFSOSHematopoietic CelP Corradini. Leukemia (2014), 17Intensified 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-

26、Ara-C 2 g/m2 Q12h d1-3AHS 淋巴瘤干细胞移植P Corradini. Leukemia (2014), 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 PTCLAHS 淋巴瘤干细胞移植P Corradini. Leukemia (2014), P Corradini. Leukemia (2014), 17 Clin B study

27、- 4 yr OS 32% - 4 yr PFS 26% - 4 yr DFS 44%Intensified chemo-immunotherapy SCT in newly diagnosed PTCLAHS 淋巴瘤干细胞移植P Corradini. Leukemia (2014), 晚期、复发NK/T 淋巴瘤AHS 淋巴瘤干细胞移植中山大学肿瘤医院2022/10/22022/10/2晚期、复发NK/T 淋巴瘤AHS 淋巴瘤干细胞移植中山大学肿，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 Tran

28、splant. 2006)AHS 淋巴瘤干细胞移植，自体外周血造血干细胞移植: NKT淋巴瘤，1st获益患者自体移植: III/IV 期和复发难治 NK/T Promising3-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AHS 淋巴瘤干细胞移植自体移植: III/IV 期和复发难治 NK/T PromYDM, 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，C

29、R ASCT 后12个月 CCRAHS 淋巴瘤干细胞移植YDM, 女，24岁，IVB NK/T 腹部巨大肿块，PS= Upfront Autologuos Stem-Cell Transplantation in Peripheral T-Cell Lymphoma: NLG-T-015y-OS 51%5y-PFS 41%J Clin Oncol.2013 May 1;31(13):1624-30.AHS 淋巴瘤干细胞移植 Upfront Autologuos Stem-4 . FL， 滤泡型淋巴瘤AHS 淋巴瘤干细胞移植中山大学肿瘤医院2022/10/22022/10/24 . FL， 滤泡

30、型淋巴瘤AHS 淋巴瘤干细胞移植中山大学Randomized Trials of Upfront Autologous Transplantation for FLTrialMeasureTransplant, %Control, %P ValueGOELAMS19-yr PFS6439.004GLSG25-yr PFS6236 .0001GELA37-yr EFS3828.11GITMO/IIL44-yr EFS6128 .0011. Gyan E, et al. Blood. 2009;113:995-1001. 2. Lenz G, et al. Blood. 2004;104:2667

31、-2674. 3. Sebban C, et al. Blood. 2006;108:2540-2544. 4. Ladetto M, et al. Blood. 2008;111:4004-4013.TrialOSTransplant, %Control, %P ValueGOELAMS19 yrs7680.55GLSG2-GELA37 yrs7671.53GITMO/IIL44 yrs8180.96AHS 淋巴瘤干细胞移植Randomized Trials of Upfront A Long term outcome of AHSCT 复发滤泡型248 pts, age 47 (20-67

32、) 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 centerAHS 淋巴瘤干细胞移植 Long term outcome of AHSCT CUP trial: PFS,1.00.80.60.40.20012 24 36 48 60 72

33、84MonthsProportion progression-freeEventsTotalChemotherapy2024Unpurged 922Purged1124Schouten H, et al. J Clin Oncol 2003;21:391827AHS 淋巴瘤干细胞移植CUP trial: PFS,1.0012 2Tandem Transplant for，双移植 Follicular NHL 3 线随访39 月, OS 96%3年PFS 96% AHS 淋巴瘤干细胞移植中山大学肿瘤医院2022/10/22022/10/2双移植 auto-allo transplant 复发难治

34、滤5 .套细胞淋巴瘤MCL,AHS 淋巴瘤干细胞移植5 .套细胞淋巴瘤MCL,AHS 淋巴瘤干细胞移植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 AHS 淋巴瘤干细胞移植1.套细胞淋巴瘤2008，2009R-CHOP + AHS年轻一线：MCL1 vs MCL 2AHS 淋巴瘤干细胞移植年轻一线：MCL1 vs MCL 2AHS 淋巴瘤干细胞移植套细胞淋巴瘤长期随访：MCL2方案AHS 淋巴瘤干细胞移植套细胞淋巴瘤长期随访：MCL2方案AHS

35、淋巴瘤干细胞移植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, 2014AHS 淋巴瘤干细胞移植360 例患者一项EBMT关于套细胞淋巴瘤移植后复发的预后因Median OS: 19mRelapesd 12mS. 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AHS 淋巴瘤干细胞移植Me

36、dian OS: 19mRelapesd 12m vsFirst line vs. salvage SCTOS after ASCT failure by timing of first ASCTOS after ASCT failure by refractory diseaseSensitive vs. refractoryS. 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AHS 淋巴瘤干细胞移植First line vs. salvage SCTOS a2000-2003

37、年 vs.2004-2007年OS after ASCT failure by calendar yearof relapseOS from 3 months landmark after ASCT failure by response to first-salvage regimen given for relapseCR vs.PR vs. SD/PDS. 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AHS 淋巴瘤干细胞移植2000-2003年 vs.2004-2007年

38、OS aftNordic 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-CRESP O NDINGCRCRu/PR Zevalin1 1w before ASCT Rituximab 250mg/m2 1 w before and just prior to Zevalin AHSCT BEAM/BEACAHS 淋巴瘤干细胞

39、移植Nordic MCL3 研究:Arne K. Blood. EFS OS PFSSurvival curves for MCL2 and MCL3Nordic 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: 2953-2959AHS 淋巴瘤干细胞移植EFS OS 移植前基于PET/CT扫描结果的生存曲线PFSOSNordic 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. B

40、lood. 2014 123: 2953-2959AHS 淋巴瘤干细胞移植移植前基于PET/CT扫描结果的生存曲线PFSOSNordi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: 2953-2959AHS 淋巴瘤干细胞移植基于微小病灶残留检测的PFS曲线移植前移植后Nordic M移植前获得CR和Cru/PR患者的DOR曲线Arne K. Blood. 2014 123: 2953-2959Nordic MCL

41、3 研究:90Y-ibritumomab-tiuxetanadded 联合BEAM/C 治疗移植前未CR的套细胞淋巴瘤AHS 淋巴瘤干细胞移植移植前获得CR和Cru/PR患者的DOR曲线Arne K. 6. Allo-HSCT 和其他AHS 淋巴瘤干细胞移植6. Allo-HSCT 和其他AHS 淋巴瘤干细胞移植Improved supportive therapy and outcome after auto vs. alloHSCT?Allogeneic SCT over timeAutologous SCT over timeBut:- retrospective study with heterogenous patient population- TBI conditioning regimen significantly lower relapse rate (p=0.02)- no specific prognostic factors after autologous/allogeneic transplantationvan Besnien et al. Blood 2003AHS 淋巴瘤干细胞移植Improved supportive therapy anZevaline + allo-