急性淋巴细胞白血病患者异基因造血干细胞移植结果与早期细胞免疫重建的相关性  

Clinical outcomes and early immune reconstitution in patients with acute lymphoblastic leukemia underwent alloge⁃neic hematopoietic stem cell transplantation

作　　者：李慧宇 崔彤 李诗佳 周士源[1] 朱文娟[1] 李静[1] 马骁[1] 吴小津[1] LI Huiyu;CUI Tong;LI Shijia;ZHOU Shiyuan;ZHU Wenjuan;LI Jing;MA Xiao;WU Xiaojin(National Clinical Research Center for Hematologic Disease,the First Affiliated Hospital of Soochow U-niversity,Jiangsu Institute of Hematology,NHC Key Laboratory of Thrombosis and Hemostasis,Suzhou 215006,China.)

机构地区：[1]国家血液系统疾病临床医学研究中心苏州大学附属第一医院江苏省血液研究所国家卫生健康委员会血栓与止血重点实验室,江苏苏州215006

出　　处：《中国输血杂志》2023年第9期777-781,共5页Chinese Journal of Blood Transfusion

基　　金：国家自然科学基金(82171159,81974001,82170222);江苏省自然科学基金(BK2021107);苏州市卫生健康委科研项目(LCZX202101);国家科技重大专项课题(2017ZX09304021);国家重点研发计划(2019YFC0840604,2017YFA0104500);江苏省临床医学中心建设(YXZXA2016002)。

摘　　要：目的 探讨接受异基因造血干细胞移植(allo-HSCT)的急性淋巴细胞白血病患者(ALL)早期免疫重建情况与移植结果的相关性。方法 收集2018年12月至2022年2月本院接受allo-HSCT的99名ALL患者的完整基本信息及治疗情况,采用流式细胞技术分别检测移植前,移植后30 d、60 d、90 d CD3+T, CD3+CD4+T, CD3+CD8+T及CD3-CD16+CD56+NK细胞比例,分析早期淋巴细胞免疫重建与粒系植入,血小板植入,感染以及急慢性移植物抗宿主病的相关性。结果 99名ALL患者粒系中位植入时间11(范围,8~28)d,巨核系中位植入时间14(范围,10~120)d。血流感染(BSI)累积发生率为11.10%,移植后100 d内巨细胞病毒(CMV)累积发生率为40.40%。100 d内EBV累积发生率为7.10%。急性移植物抗宿主病(aGVHD)累积发生率22.30%。移植后1年内发生广泛慢性移植物抗宿主病(cGVHD)累积发生率16.20%。1年累积复发率13.84%。所有患者1年累积无病生存率(DFS)为80.60%,1年总生存率(OS)为90.30%。移植后30 d, CD4+/CD8+比值与aGVHD的发生正相关(OR 1.21,95CI 1.01~1.45,P<0.05)。移植前及移植后30 d,无BSI发生组CD16+CD56+NK细胞绝对计数高于BSI组,差异具有统计学意义(P<0.05)。移植后60 d和90 d, CMV感染组CD4+T细胞绝对计数均低于无CMV感染组,差异有统计学意义(P<0.05),多因素分析提示移植后60 d较高水平的CD4+T细胞是发生100 d内CMV感染的保护性因素(HR 0.91, 95CI 0.84~0.99,P<0.05)。结论 ALL患者接受allo-HSCT后早期淋巴细胞亚群重建跟aGVHD,CMV和BSI等临床事件存在一定相关性。Objective To investigate the correlation between early immune reconstitution and clinical outcomes in pa⁃tients with acute lymphoblastic leukemia(ALL)underwent allogeneic hematopoietic stem cell transplantation(allo⁃HSCT).Methods The basic information and treatment data of 99 patients with ALL undering allo⁃HSCT from December 2018 to February 2022 were collected.The proportions of CD3+T,CD3+CD4+T,CD3+CD8+T and CD3-CD16+CD56+NK cells were detected before and 30,60 and 90 days after transplantation using flow cytometry.The correlation between early cellular immune reconstitution and neutrophil engraftment,platelet engraftment,infection,and acute and chronic graft⁃versus⁃host disease(GVHD)was analyzed.Results Among 99 ALL patients,the median time of neutrophil engraftment was day+11(range,8-28),and the median time of platelet engraftment was day+14(range,10-120).The cumulative incidence of blood stream infection(BSI)was 11.10%and the cumulative incidence of CMV within 100 days of transplantation was 40.40%.The cumulative incidence of EBV within 100 days was 7.10%.The cumulative incidence of acute graft⁃versus⁃host disease(aGVHD)was 22.30%.The cumulative incidence of chronic graft⁃versus⁃host disease(cGVHD)within 1 year of transplantation was 16.20%.1⁃year cumulative relapse rate was 13.84%.The 1⁃year cumulative disease⁃free survival(DFS)for all patients was 80.60%and the 1⁃year overall survival(OS)was 90.30%.The CD4+/CD8+ratio was positively associated with the development of aGVHD at 30 days post⁃transplant(OR 1.21,95CI 1.01-1.45,P<0.05).The proportion of CD16+CD56+NK cell were higher in the group without BSI than that in the BSI group before and 30 days after transplantation(P<0.05). The proportion of CD4+ T⁃cell were lower in the CMV infection group than that in the group without CMV infection at60 and 90 days post⁃transplant(P<0.05). The higher level of CD4+ T⁃cells at 60 days post⁃transplant was a protective factorfor CMV infection within 100 days (HR 0.91, 95CI 0.84-0.99, P<

关 键 词：异基因造血干细胞移植 急性淋巴细胞白血病 免疫重建 血流感染 CMV感染 

分 类 号：R733.71[医药卫生—肿瘤]