异基因造血干细胞移植挽救性治疗复发难治淋巴瘤临床研究

摘要

目的:探讨异基因造血干细胞移植(allo-HSCT)挽救性治疗复发难治淋巴瘤的疗效及其相关影响因素与安全性.方法:2004年3月至2015年2月应用allo-HSCT挽救性治疗复发难治淋巴瘤31例,采用的预处理方案包括以BEAM为基础的预处理(12例)、以改良的Bu/Cy为基础的预处理(11例)、以Cy/TBI为基础的预处理(6例)及Bu/Cy预处理(1例).对GVHD预防采用在CsA联合短程MTX的经典方案基础上加用MMF.输注的HSC包括全相合亲缘供者HSC(11例)、半相合亲缘供者HSC(13例)及非亲缘相合供者HSC(6例).输注骨髓联合外周血HSC的21例,仅输注外周血HSC的9例.31例中男18例,女13例,中位年龄31(13-52)岁.其中霍奇金淋巴瘤(HL)4例,非霍奇金淋巴瘤(NHL) 27例.移植前全部病例处于疾病未缓解或进展状态.结果:经allo-HSCT后27例患者获得造血重建,白细胞(WBC)植活中位时间12(10-20)d,血小板(Plt)植活中位时间13(9-34)d.Ⅱ-Ⅳ度急性GVHD (aGVHD)9例,慢性GVHD(cGVHD)3例.移植后未缓解5例,缓解后再复发6例.至2015年9月,中位随访时间11.5(0-141)月,存活15例,2年总生存率46.1％±9.5％.单因素分析显示,年龄(P＜0.05),移植前疾病状态(P＜0.05)和移植后是否缓解(P＜0.01)是影响患者生存的因素.多因素分析显示,移植前疾病状态(P＜0.05)和年龄(P＜0.05)是a11o-HSCT治疗难治复发淋巴瘤的独立预后因素.结论:allo-HSCT治疗复发难治淋巴瘤安全有效,可以作为挽救性治疗的关键措施广泛应用于临床.%Objective:To assess the safety and efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in treating patients with relapsed and refractory lymphoma.Methods:Thirty-one consecutive patients with relapsed or refractory lymphoma received allo-HSCT.Used conditioning regimens included conditioning based on BEAM regimen(12 cases),conditioning based on modified Btt/Cy regimen(11 cases),conditioning based on Cy/TBI regemen (6 cases) and conditioning of Bu/Cy regimen(1 case).For provention of GVHD,the MMF was used on the basis of classcal protocol consisting of CsA combined with MTX.The infused HSC included the HLA-matched related HSC (11 cases),HLA nonidentical related HSC (13 cases) and HLA-matched unrelated HSC (6 cases).The bone marrow plus peripheral blood HSC were infused in 21 cases,while only peripheral blood HSC were infused in 9 cases.Among the 31 cases of relapse/refractory lymphoma,18 patients were male and 13 were female,4 cases were Hodgkin's lymphoma and 27 cases were non-Hodgkin's lymphoma.ALL of the 31 patients were qualified,as they were not in complete remission (CR) or in advanced stage at the time of transplantation.Results:Twenty-seven evaluable patients showed the engraftment of both neutrophil and platelet at a median of 12 days (range 10-20) and 13 days (range 9-34) respectively,9 cases developed Ⅱ-Ⅳ aGVHD,and cGVHD was observed in 3 patients,5 patients can not achieve CR at 3 months after transplantation,and 6 patients relapsed after CR,the median follow-up of all the 31 patients after transplantation was 11.5 months (ranged,0-141 months),and the 2-year OS was 46.1％-±9.5％ with median survival of 40 (9-141)months in the 15 survivors.The age (P ＜ 0.05),disease status before transplantation (P =0.020) and remission after transplantation(P =0.000) were significantly related with survival.Cox's proportional hazards regression model analysis showed that the age (P =0.041) and disease statue (P =0.020) before allo-HSCT were independent predictive factors for survival.Conclusion:Allo-HSCT is an optimal treatment strategy for the patients with relapsed and refractory lymphoma who failed to most,if not all,available options.