重型地中海贫血患儿异基因造血干细胞移植后淋巴增殖性疾病的危险因素分析  

Risk factors for lymphoproliferative disorders after allogeneic hematopoietic stem cell transplantation in children with thalassemia major

作　　者：罗小娟[1] 董春苗 曹科[1] 黄涛 王春静[3] 李越[3] 杨春兰[3] 任振敏 付笑迎[1] 陈运生[1] Luo Xiaojuan;Dong Chunmiao;Cao Ke;Huang Tao;Wang Chunjing;Li Yue;Yang Chunlan;Ren Zhenmin;Fu Xiaoying;Chen Yunsheng(Department of Clinical Laboratory,Shenzhen Children′s Hospital,Shenzhen 518038,China;Medical College of Jiaying University,Meizhou 514031,China;Department of Hematology and Oncology,Shenzhen Children′s Hospital,Shenzhen 518038,China)

机构地区：[1]深圳市儿童医院检验科,深圳518038 [2]嘉应学院医学院,梅州514031 [3]深圳市儿童医院血液肿瘤科,深圳518038

出　　处：《中华实用儿科临床杂志》2024年第12期917-921,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：广东省基础与应用基础研究基金企业联合基金(2021A1515220072,2022A1515220033,2023A1515220156);广东省高水平医院建设专项经费资助;深圳市科技创新委员会基础研究面上项目(JCYJ20220530155811025,JCYJ20230807093820041)。

摘　　要：目的探讨重型地中海贫血(TM)患儿异基因造血干细胞移植(allo-HSCT)术后并发淋巴增殖性疾病(PTLD)的危险因素。方法回顾性病例对照研究。以2020年1月至2022年12月在深圳市儿童医院行allo-HSCT的482例TM患儿为研究对象,根据是否发生PTLD分为PTLD组和非PTLD组,分析TM患儿allo-HSCT术后并发PTLD的危险因素,并通过受试者工作特征(ROC)曲线分析相关危险因素预测PTLD的效能。结果482例患儿中25例发生PTLD,发生率为5.2%(25/482),发生时间为移植后114.0(54.0~271.0)d,其中12例(12/25,48.0%)发生在术后100 d内,22例(22/25,88.0%)发生在术后1年内。单因素分析显示,2组间性别构成、移植供者类型、术后30 d外周血自然杀伤和B细胞数、血浆EB病毒核酸(EBV-DNA)阳性率和急性移植物抗宿主病(aGVHD)发生率比较差异均有统计学意义(均P<0.05)。多因素Logistic回归分析显示,患儿性别为女性(OR=3.196,95%CI:1.144~8.929)、血浆EBV-DNA阳性(OR=17.523,95%CI:5.449~56.344)和发生aGVHD(OR=3.156,95%CI:1.161~8.575)是TM患儿allo-HSCT后并发PTLD的独立危险因素(均P<0.05)。ROC曲线分析显示,血浆EBV-DNA阳性预测allo-HSCT后发生PTLD具有较高的准确性(灵敏度0.796,特异度0.800,曲线下面积0.803),联合aGVHD和性别指标,曲线下面积提高至0.831。结论性别为女性、血浆EBV-DNA阳性和发生aGVHD是TM患儿allo-HSCT术后并发PTLD的独立危险因素,对PTLD的早期预测和预防有一定预警作用。ObjectiveTo explore the risk factors for lymphoproliferative disorders(PTLD)in children with thalassemia major(TM)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).MethodsThis was a retrospective case-control study.A total of 482 children with TM who underwent allo-HSCT at Shenzhen Children′s Hospital between January 2020 and December 2022 were selected and classified into the PTLD and non-PTLD groups according to the occurrence of PTLD.The risk factors for PTLD after allo-HSCT in children with TM were analyzed,and the diagnostic efficiency of relevant risk factors for PTLD was analyzed by receiver operating characteristic(ROC)curve.ResultsA total of 25 out of 482 patients(5.2%,25/482)developed PTLD about 114(54-271)days after allo-HSCT.Among them,12 cases(12/25,48.0%)occurred within 100 days,and 22 cases(22/25,88.0%)occurred within 1 year after allo-HSCT.Univariate analysis showed that there were significant differences in gender composition,type of transplant donor,number of natural killer cells and B lymphocytes in peripheral blood at 30 days after allo-HSCT,positive rate of plasma Epstein-Barr virus deoxyribonucleic acid(EBV-DNA)and incidence rate of acute graft-versus-host disease(aGVHD)between the 2 groups(all P<0.05).Multivariate Logistic regression analysis showed that female(OR=3.196,95%CI:1.144-8.929),positive plasma EBV-DNA(OR=17.523,95%CI:5.449-56.344)and aGVHD(OR=3.156,95%CI:1.161-8.575)were independent risk factors for PTLD after allo-HSCT in TM children(all P<0.05).The ROC curve analysis showed that positive plasma EBV-DNA had an excellent accuracy in predicting the occurrence of PTLD after allo-HSCT(sensitivity was 0.796,specificity was 0.800,area under the curve was 0.803).If combined with aGVHD and gender,the area under the curve for the prediction of PTLD increased to 0.831.ConclusionsFemale,positive plasma EBV-DNA and aGVHD are independent risk factors for PTLD after allo-HSCT in children with TM.It provides useful early warnings for the prediction and prevention of PTLD.

关 键 词：地中海贫血 造血干细胞移植 移植后淋巴增殖性疾病 危险因素 

分 类 号：R725.5[医药卫生—儿科]