57例急性淋巴细胞白血病异基因造血干细胞移植后抗宿主病的发生及影响因素分析  

Graft-versus-host disease secondary to allogeneic hematopoietic stem cell transplantation in 57 patients with acute lymphoblastic leukemia

作　　者：孙菲菲[1] 房孝生[1] 姜玉杰[1] 隋潇徽[1] 刘新[1] 王相华[1] 李英[1] 张凌岩[1] 许洪志[1] 王欣[1] SUN Feifei;FANG Xiaosheng;JIANG Yujie;SUI Xiaohui;LIU Xin;WANG Xianghua;LI Ying;ZHANG Lingyan;XU Hongzhi;WANG Xin(Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong University,Jinan 250021,Shandong,China)

机构地区：[1]山东大学附属省立医院血液科

出　　处：《山东大学学报（医学版）》2019年第7期61-66,共6页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81270598,81473486,81770210);山东省重大科技创新工程(2018CXGC1213);山东省重点研发计划(2017GSF1819,2016GSF201029);济南市科技发展计划(201705008)

摘　　要：目的探讨急性淋巴细胞白血病(ALL)异基因造血干细胞移植(allo-HSCT)后移植物抗宿主病(GVHD)的发生率,对预后的影响及其危险因素。方法收集2010年10月1日至2018年10月1日山东省立医院血液内科接受allo-HSCT的ALL患者57例,统计原发病基本情况、造血干细胞移植情况、移植物抗宿主病、复发生存等情况,分析移植物抗宿主病的发生率、严重程度以及危险因素。结果人类白细胞抗原(HLA)不全相合移植37例,HLA全相合移植20例,2例非血缘全相合移植。供受者血型相合24例,血型不相合33例;同性别移植30例,非同性别移植27例。巨核系中位植入时间13 d(9~47 d),粒系中位植入时间12 d(6~20 d)。急性移植物抗宿主病(aGVHD)累积发生率53.4%,其中Ⅰ~Ⅱ度为42.8%,Ⅲ~Ⅳ度为10.8%。慢性移植物抗宿主病(cGVHD)累积发生率20.3%,其中广泛型cGVHD为5.3%,局限型cGVHD为15.1%。生存分析显示Ⅲ~Ⅳ度aGVHD患者3年生存(OS)率、无白血病生存(LFS)率较无aGVHD及Ⅰ~Ⅱ度aGVHD患者减低(20%vs 69.8%、66.7%,χ~2=17.243,P<0.001;20%vs 60.8%、71%,χ~2=9.463,P=0.009),且复发率(RR)及非复发死亡(NRM)升高(60%vs 33.7%、23.9%,χ~2=1.788,P=0.409;50%vs 0.71%、0.59%,χ~2=21.344,P<0.001)。cGVHD较无cGVHD患者3年OS、LFS减低,差异无统计学意义(44.4%vs 67.6%,χ~2=0.142,P=0.706;50%vs 62.4%,χ~2=0.236,P=0.627)。多因素分析显示,HLA配型不合为aGVHD发生的独立危险因素,HLA不全相合较HLA全相合移植aGVHD发生率增加。供受者性别不同为cGVHD的边缘性独立影响因素,非同性别移植较同性别移植cGVHD发生率增加。结论 GVHD是ALL患者行allo-HSCT的重要并发症,Ⅲ~Ⅳ度aGVHD预后不良,HLA配型不合为发生aGVHD的独立危险因素。Objective To explore the incidence and risk factors of graft-versus-host disease(GVHD) secondary to allogeneic hematopoietic stem cell transplantation(allo-HSCT) in patients with acute lymphoblastic leukemia(ALL). Methods The clinical data of 57 ALL patients who received allo-HSCT in our hospital during Oct. 2010 and Oct. 2018 were retrospectively analyzed. The information primary diseases, HSCT, overall survival(OS), leukemia-free survival(LFS), relapse rate(RR) and non-relapse mortality(NRM) was collected. The incidence, severity and risk factors of GVHD were analyzed. Results The donors were human leukocyte antigen(HLA)-allele mismatched for 37 cases, and matched for 20 cases(2 of which were unrelated). The donors for 24 cases had the identical blood type as the recipients, while donors for 37 cases had incompatible blood type. The donors for 30 cases were the same gender as the recipients, while donors for 27 cases were different gender. Median day of neutrophil and platelet engraftment was 12 d(range: 6-20 d) and 13 d(range: 9-47 d), respectively. Accumulative incidence of acute GVHD(aGVHD) was 53.4%(grade Ⅰ-Ⅱ: 42.8%;grade Ⅲ-Ⅳ: 10.8%). The cumulative incidence of chronic GVHD(cGVHD) was 20.3%, of which 5.3% was extensive and 15.1% was limited. Survival analysis showed that the 3-year OS and LFS of patients with grade Ⅲ-Ⅳ aGVHD were significantly lower than those without or with grade Ⅰ-Ⅱ aGVHD(20% vs 69.8%, 66.7%, χ^2=17.243, P<0.001;20% vs 60.8%, 71%, χ^2=9.463, P=0.009), with RR and NRM increased(60% vs 33.7%, 23.9%, χ^2=1.788, P=0.409;50% vs 0.71%, 0.59%, χ^2=21.344, P<0.001). The 3-year OS and LFS of patients with cGVHD were lower than those without cGVHD by no significant difference(44.4% vs 67.6%, χ^2=0.142, P=0.706;50% vs 62.4%, χ^2=0.236, P=0.627). Multivariate analysis showed that HLA mismatch was a significantly independent risk factor for aGVHD. Gender difference between donors and recipients was an marginally significant independent factor of cGVHD. Conclusion GVHD is an imp

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 供受者性别 人类白细胞抗原 

分 类 号：R733.71[医药卫生—肿瘤]