AHS 淋巴瘤干细胞移植

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,CLICK TO EDIT MASTER TITLE STYLE,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,New Slide,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,CLICK TO EDIT MASTER TITLE STYLE,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,New Slide,*,CLICK TO EDIT MASTER TITLE STYLE,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,New Slide,*,CLICK TO EDIT MASTER TITLE STYLE,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,New Slide,*,CLICK TO EDIT MASTER TITLE STYLE,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,New Slide,*,CLICK TO EDIT MASTER TITLE STYLE,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,New Slide,*,CLICK TO EDIT MASTER TITLE STYLE,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,New Slide,*,CLICK TO EDIT MASTER TITLE STYLE,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,New Slide,*,CLICK TO EDIT MASTER TITLE STYLE,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,New Slide,*,CLICK TO EDIT MASTER TITLE STYLE,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,New Slide,*,CLICK TO EDIT MASTER TITLE STYLE,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,New Slide,*,CLICK TO EDIT MASTER TITLE STYLE,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,New Slide,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,*,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),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 ：,4,21,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：,34,60,复发难治,HL PET/CT,结果与自体移植的疗效关系,Haematologica 2012,PET/CT -,PET/CT +,中山大学肿瘤医院,SUN YAT-SEN UNIVERSITY CANCER CENTER,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,1998-2009,100 pts,BuMelTt,(busulfan, melphalan,thiotepa): 60pts,Others:40pts,CBV(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 55(3): 583587,PFS,OS,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 73,40,19,9,R-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,CR,Biol 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 year,Japan Society for HCT database,484 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 1,st,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/m,2,- Zevalin 0.4 mCi/kg d -14,- Carmustine 300 mg/m,2,d -6,- Etoposide 200 mg/m,2,d -5 - -2,- Cytarabine 200 mg/m,2,Q12h d -5 - -2,- Melphalan 140 mg/m,2,d -1,Cancer.,2012 Oct 1;118(19):4706-14,),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 pts,without CR to salvage chemotherapy,6 pts RIT combined with HD-chemotherapy,8 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 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,Restaged,at 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 Mature,T-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 outcomes,PFS,NRM,OS,alloHCT,N=126,OS,PFS,NRM,NRM,PFS,OS,Sonali M. J Clin Oncol 31:3100-3109,.,Hematopoietic Cell Transplantation for Systemic Mature,T-Cell Non-Hodgkin Lymphoma,PFS,OS,NRM,PFS,OS,Hematopoietic Cell Transplantation for Systemic Mature,T-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,Trial,Measure,Transplant, %,Control, %,P,Value,GOELAMS,1,9-yr PFS,64,39,.004,GLSG,2,5-yr PFS,62,36, .0001,GELA,3,7-yr EFS,38,28,.11,GITMO/IIL,4,4-yr EFS,61,28, .001,1. 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.,Trial,OS,Transplant, %,Control, %,P,Value,GOELAMS,1,9 yrs,76,80,.55,GLSG,2,-,-,-,GELA,3,7 yrs,76,71,.53,GITMO/IIL,4,4 yrs,81,80,.96,Long term outcome of AHSCT,复发滤泡型,248 pts, age 47 (20-67) y,Median prior chemotherapies 2, 110 pts AHSCT only,Median F/U,6 years,( 1-16 ) y,47% progression,13% died without NHL,44% 5Y EFS,63% 5y OS,2005 ASCO ,abstract 6567,J Vose et al University of Nebraska medical center,CUP trial: PFS,0,012 24 36 48 60 72 84,Months,Proportion progression-free,EventsTotal,Chemotherapy2024,Unpurged 922,Purged1124,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,年年,OS after ASCT failure by calendar year,of 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,:,90,Y-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,R,E,S,P O N,D,I,N,G,CR,CRu/PR,Zevalin1,1w before ASCT,Rituximab 250mg/m,2,1 w before and just,prior to Zevalin,AHSCT,BEAM/BEAC,EFS OS PFS,Survival curves for MCL2 and MCL3,Nordic MCL3,研究,:,90,Y-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,:,90,Y-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,:,90,Y-ibritu