AHS淋巴瘤干细胞移植.ppt
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1、,自体造血干细胞移植治疗恶性淋巴瘤应用进展,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:
2、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,thiotep
3、a):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 55(3):583587,PFS,OS,P=0.03,P=0.05,2.NHL,DLBCL弥漫大B
4、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
5、,Overall survival,CORAL研究:移植后疗效 EFS,Failure from diagnosis=12 months,Failure from diagnosis 12 months,Failure from diagnosis=12 months,Standard salvage regimen does not overcome poor prognosis of early relapse,Rituximab-化疗复发:自体移植的疗效,Br J Haematol.2014 Mar;164(5):668-74.有研究提示,美罗华化疗后复发患者自体移植效果差?移植后 5年
6、 R+vs R-PFS 63%48%OS 72%61%美罗华治疗后不会影响移植效果,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,弥漫大B淋巴瘤:一线,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,美罗华之前:ASHCT DLBCL 1st,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,Advances in Hematology,2012 意大利,DLBCL一线治疗:HDCT试验的荟萃分析,Greb et al.,2007,Cancer Treat Rev,美罗
7、华时代:自体移植疗效,1st,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,Advances in Hematology,2012 意大利,自体移植+/-rituximab 治疗初治高危弥漫大BNHL,III期随机对照,OS,EFS,Annals of Oncology Advance Access published May 5,2010,Dose-dense and high-dose chemotherapy plus rituximab+ASHSCT for primary treatment of DLBCLwith a poor prog
8、nosis:a phase II multicenter study,R-HDC,HDC,R-HDC,HDC,haematologica|2009;94(9),R-HDC,HDC,HDC,R-HDC,SWOG-9704 研究设计,Stiff P,et al.N Engl J Med 2013;369(18):1681-1690.,SWOG-9704 显示:移植组较对照组显著延长2年PFS,但是OS上无差别,Stiff P,et al.N Engl J Med 2013;369(18):1681-1690.,SWOG-9704亚组分析显示:移植组在aaIPI为3分的患者中可以较对照组明显延长患者
9、PFS,Stiff P,et al.N Engl J Med 2013;369(18):1681-1690.,SWOG-9704亚组分析显示:移植组在aaIPI为3分的患者中可以较对照组明显延长患者OS,Stiff P,et al.N Engl J Med 2013;369(18):1681-1690.,原发中枢淋巴瘤:自体移植价值HD AraC+VP16(CYVE)+HDCT(TT-BU-CY)as salvage for relapse/resistant PCNSL,2011 updateN=60,median FU 5yOS chemosensitive 97 m chemoresis
10、tant 18 m ICML 2011 Abstr.035,Resp+HDCT,No Resp+HDCT,Resp no HDCT,NO resp no HDCT,中山大学肿瘤医院SUN YAT-SEN UNIVERSITY CANCER CENTER,继发中枢淋巴瘤移植效果好!,化疗敏感 62%vs 不敏感36.2%,Thiotepa,busulfan and cyclophosphamide+AHSCT,复发难治原发中枢淋巴瘤,5yOS,CR 56.4%vs 未CR 31.1%,Haematologica.2012 Nov;97(11):1751-6.,AHSCT前CR/PR,移植后CR患
11、者(5y-OS 62%)AHSCT前SD/PD,移植后CR患者(5y-OS 38.9%)移植后未获得CR患者(5y-OS 31.1%),Thiotepa,busulfan and CTX+AHSCT for relapsed or refractory PCNSL/PLOT,Haematologica.2012 Nov;97(11):1751-6.,2000 至2010 年27例中位年龄:59岁中位 ECOG评分:276%DLBCL中位OS 7月1年OS:62%,自体移植治疗淋巴瘤继发中枢侵犯 an International Primary CNSL Study Group project,
12、ASCT:DLBCL临床资料,70例,中山大学肿瘤医院男性41例,女性29例中位年龄43岁(21-76岁)中位随访时间35.5月(月)因肿瘤死亡29例,DLBCL OS 生存曲线 中山大学肿瘤医院,1年OS 91.0%,3年OS 77.7%,5年OS 56.9%,AHSCT:复发难治老年DLBCL-日本血液学协会回顾性研究,2013ASH,1993-2010年484pts中位64岁(60-78)中位随访26.5月移植相关死亡-4.1%(100天)-5.9%(1年)-10.7%3年)2年 PFS 48%,OS 58%60-64,65-69,70岁,移植相关死亡无差异OS预后因素:70岁,PS 2
13、-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%
14、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:
15、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%656
16、9 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 Ag
17、gressive 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
18、%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-
19、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
20、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
21、 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,Pidilizuma
22、b(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
23、 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-SE
24、N 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
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- AHS 淋巴瘤 干细胞 移植
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