单倍体与同胞全相合造血干细胞移植治疗高危急性淋巴细胞白血病疗效观察  

Efficacy of haploid-matched vs sibling-matched allogeneic stem cell transplantation for high risk acute lymphoblastic leukemia

作　　者：颜红菊[1] 唐伦[1] 高蕾[1] 张诚[1] 刘耀[1] 高力[1] 孔佩艳[1] 刘红[1] 张曦[1] 

机构地区：[1]第三军医大学新桥医院全军血液病中心,重庆400037

出　　处：《第三军医大学学报》2016年第12期1340-1346,共7页Journal of Third Military Medical University

基　　金：国家自然科学基金面上项目(81570097);全军后勤科研"十二五"重大子项目(AWS14C0143)~~

摘　　要：目的分析异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation,AlloHSCT）治疗高危急性淋巴细胞白血病（acute lymphoblastic leukemia,ALL）的疗效,并探讨临床预后因素。方法对我院2007年7月至2013年8月进行Allo-HSCT治疗并随访2年以上的69例ALL患者进行临床分析。按移植方式分为单倍体组（n=42）和全相合组（n=27）,对各组患者的临床特征及治疗转归进行回顾性分析,应用Kaplan-Meier法进行生存分析,COX回归模型进行多因素预后分析。结果单倍体组2年总体生存率（overall survival,OS）及2年无白血病生存率（leukemia-free survival,LFS）分别是63.4%、59.4%,而全相合组分别是53.9%、53.7%,两组间差异均无统计学意义（P〉0.05）;两组间2年累积非复发死亡率（cumulative non-relapse mortality,NRM）差异也无统计学意义（P〉0.05）;但2年累积复发率（cumulative relapse rate,RR）单倍体组明显高于全相合组（39.5%vs 19.5%,P=0.014）。造血重建方面,单倍体组中性粒细胞植入时间明显晚于全相合移植组（P=0.002）,两组血小板植入时间无明显差异（P=0.072）。单倍体组Ⅰ~Ⅱ度急性移植物抗宿主病（graft-versus-host disease,GVHD）发生率明显高于全相合组（P=0.008）,两组间Ⅲ~Ⅳ度急性GVHD及慢性GVHD发生率差异无统计学意义（P〉0.05）。单倍体组半年内的感染率明显高于全相合组（P=0.02）。COX多因素分析显示患者移植前的疾病状态（非CR1）为异基因移植患者的危险因素（P=0.001）,其危险度为7.581;而发生局限性慢性GVHD和初诊距离移植时间较短者为预后保护因素（P=0.013和P=0.012）,危险度分别为0.178和0.688。结论在高危组ALL患者的治疗中,单倍体Allo-HSCT与全相合Allo-HSCT的整体疗效相当,因此,单倍体供者可以作为合适的造血干细胞来源。Objective To determine the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation（ allo-HSCT） in the treatment of high risk acute lymphoblastic leukemia（ ALL）.Methods A total of 69 ALL patients treated with allo-HSCT in our center from July 2007 to August 2013 and followed up for more than 2 years after transplantation were enrolled in this study. According to transplantation types,they were divided into haploid-matched group（ n = 42） and sibling-matched group（ n = 27）. Clinical characteristics and efficacy of 2 groups were retrospectively analyzed. Their survival was analyzed by the Kaplan-Meier method and the prognostic factors were analyzed with COX regression model. Results The 2-years overall survival（ OS） and 2-year leukemia-free survival（ LFS） were 63. 4% and 59. 4%,in the haploid-matched group,and 53. 9% and 53. 7%,in the sibling-matched group（ P 0. 05）. There was no significant difference in 2-year non-relapse mortality（ NRM） between the 2 group（ P 0. 05）,but was in 2-year cumulative relapse rate（ RR）,with that of haploid-matched group obviously higher than that of siblingmatched group（ 39. 5% vs 19. 5%,P = 0. 014）. In hematopoietic reconstruction,neutrophils reconstruction was remarkably slower in the haploid-matched group than the sibling-matched group（ P = 0. 002）,but platelet reconstruction was similar（ P = 0. 072）. The incidence of grade Ⅰ ~ Ⅱ acute graft-versus-host disease（ a GVHD） was obviously higher in haploid-matched group than sibling-matched group（ P = 0. 008）,but those of grade Ⅲ ~ Ⅳ a GVHD and c GVHD were similar in the 2 groups（ P 0. 05）. The early infection incidents after HSCT（ within 6 months） was obviously higher in the haploid-matched group than sibling-matched group（ P = 0. 02）. Cox regression analysis showed that disease status before transplantation（ not CR1） was a main risk factor for allo-HSCT（ P = 0. 001）,with a relative risk of 7. 581. The limited chronic GVHD

关 键 词：急性淋巴细胞白血病 异基因造血干细胞移植 移植物抗宿主病 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R617[医药卫生—基础医学]