HLA单倍体相合与全相合allo-HSCT治疗难治复发NHL的疗效和安全性对比  

Haploidentical hematopoietic stem cell transplantationversus HLA-matched stem cell transplantation for refractory or relapsed aggressive non-Hodgkin lymphoma

作　　者：朱倩[1] 黄海雯[1] 肖小芳 张丽红 刘硕 陈晓晨[1] 金正明[1] 吴德沛[1] Zhu Qian;Huang Haiwen;Xiao Xiaofang;Zhang Lihong;Liu Shuo;Chen Xiaochen;Jin Zhengming;Wu Depei(Department of Hematology,First Affiliated Hospital,Soochow University,Jiangsu Provincial Institute of Hematology,Key Laboratory of Thrombosis&Hemostasis under Ministry of Health,Suzhou 215006,China)

机构地区：[1]苏州大学附属第一医院血液科江苏省血液研究所卫生部血栓与止血重点实验室,215006

出　　处：《中华器官移植杂志》2021年第10期604-609,共6页Chinese Journal of Organ Transplantation

基　　金：国家血液病临床医学研究中心转换研究开发课题基金(2020ZKMB02)。

摘　　要：目的探讨人类白细胞抗原(HLA)单倍体相合与全相合异基因造血干细胞移植(allo-HSCT)治疗难治复发非霍奇金淋巴瘤(NHL)的临床疗效。方法回顾性分析苏州大学附属第一医院血液科2006年1月至2018年12月期间151例行allo-HSCT治疗的难治复发NHL患者的临床资料,其中HLA单倍体相合81例,全相合70例。随访观察至2019年5月31日,对比两组在造血重建、总存活率、无进展生存率、移植物抗宿主反应(GVHD)发生率、非复发死亡率、复发率等方面的差异,并对预后因素进行分析。结果146例受者成功植入。单倍体组粒系重建中位时间为12 d(9~27 d),巨核系重建中位时间为15 d(9~63 d),全相合组分别为12 d(9~25 d)和15 d(10~71 d),两组之间差异无统计学意义(P=0.42,P=0.30)。中位随访时间为19个月(1~145个月),生存分析显示在单倍体组和全相合组中,2年无进展存活率为49.4%和50.5%(P=0.577),2年总体存活率为56.7%和57.4%(P=0.963),2年累积复发率为36.6%和37.7%(P=0.836),2年非复发死亡率为22.0%和24.7%(P=0.530),Ⅲ~Ⅳ度急性GVHD(aGVHD)的累积发生率为25.9%和17.1%(P=0.208),2年慢性GVHD(cGVHD)的累及发生率为42.3%和39.6%(P=0.46),差异均无统计学意义。单因素预后分析结果提示Ⅲ~Ⅳ度aGVHD、移植前处于未缓解状态、预处理前乳酸脱氢酶高水平是预后不良因素,而发生cGVHD则可改善预后。多因素分析提示移植前状态及发生cGVHD均为独立预后因素。结论单倍体造血干细胞移植在治疗难治复发NHL中可取得与全相合相似的疗效及安全性,是难治复发NHL患者无全相合供者的合适替代选择。Objective To examine the efficacy of haploidentical stem-cell transplantation(haplo-SCT)for patients with refractory relapsed(R/R)non-Hodgkin lymphoma(NHL)by comparing with those contemporaneously undergoing HLA-matched SCT in myeloablative conditioning settings.Methods Between January 2006 and December 2018,a total of 151 patients undergoing haplo-SCT(n=81)or HLA-matched SCT(n=70,sibling or unrelated)were enrolled.Median age of alloSCT was 30(5-59)years.And 150 patients received myeloablative conditioning(MAC)consisting of total body irradiation(12 Gy)plus cyclophosphamide or busulfan plus cyclophosphamide.Only one case had reduced intensity conditioning(RIC)with R-FBA(fludarabine,busulfan&cytarabina).It was followed by an infusion of granulocyte-colony stimulating factor-primed bone marrow(G-BM)and/or peripheral blood stem cells without in vitro T cell depletion.In haplo-SCT and HLA-matched unrelated donor for SCT,GVHD prophylaxis consisted of antithymocyte globulin,cyclosporine A,mycophenolate mofetil and a short course of methotrexate.Clinical efficacy,hematopoietic reconstitution and transplant-related complications were retrospectively analyzed.Results Among them,146(96%)patients engrafted with a median time to neutrophil and platelet recovery of 12 and 15 days respectively.During a median follow-up period of 19 months,66 of them survived(43.7%)and 67(44.4%)died(39 disease recurrence,27 transplantation-related mortality).Between haplo-SCT and HLA-matched SCT groups,progression-free survival(PFS)rate was 49.4%and 50.5%(P=0.577);overall survival(OS)rate 56.7%and 57.4%respectively(P=0.963).The cumulative incidences of relapse(CIR)were 36.6%and 37.7%(P=0.836)and those of cumulative incidences of non-relapse mortality(NRM)22.0%and 24.7%(P=0.530).And the cumulative incidences of chronic GVHD were 42.3%and 39.6%(P=0.46)respectively.Conclusions No inter-group difference exists in each major HSCT endpoint.Multivariate analysis reveals that occurrence of gradeⅢ-ⅣaGVHD has a significantly worse prognosis.And prima

关 键 词：造血干细胞移植 非霍奇金淋巴瘤 人类白细胞抗原 

分 类 号：R733.1[医药卫生—肿瘤]