人类白细胞抗原相合同胞新鲜脐血移植治疗儿童β重型地中海贫血  

Human leukocyte antigen matched sibling fresh cord blood transplantation for beta-thalassaemia major in children

作　　者：温建芸[1] 陈丽白[1] 何岳林[1] 冯晓勤[1] 刘璇[1] 徐肖肖 李秀 刘秋君[1] 吴学东[1] Wen Jianyun;Chen Libai;He Yuelin;Feng Xiaoqin;Liu Xuan;Xu Xiaoxiao;Li Xiu;Liu Qiujun;Wu Xuedong(Department of Pediatrics,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong Province,China)

机构地区：[1]南方医科大学南方医院儿科,广东省广州市510515

出　　处：《中国组织工程研究》2025年第23期4899-4906,共8页Chinese Journal of Tissue Engineering Research

基　　金：广东省基础与应用基础研究基金企业联合基金项目(2022A1515220153),项目名称:基于三代测序平台的地中海贫血全面诊断体系的研发与应用,项目负责人:吴学东。

摘　　要：背景:异基因造血干细胞移植是目前根治重型地中海贫血最有效的方法,然而仅有不到一半的患者能找到相合的骨髓或外周血干细胞。同胞来源脐血干细胞与骨髓和外周血干细胞具有不同的特征,是重型地中海贫血患者移植治疗的一种潜在造血干细胞替代来源。目的:探讨应用人类白细胞抗原相合同胞新鲜脐血移植治疗儿童β重型地中海贫血的疗效。方法:选择2010年6月至2020年6月南方医科大学南方医院收治的β重型地中海贫血患儿48例,男28例,女20例,中位年龄4岁,均接受人类白细胞抗原相合同胞新鲜脐血移植治疗,脐血移植前均采用清髓性不含抗胸腺细胞球蛋白的预处理方案,脐血移植后均采用环孢素A+吗替麦考酚酯+/-短程甲氨蝶呤预防移植物抗宿主病。结果与结论:(1)48例患儿输注的总有核细胞中位数为8.17×10^(7)/kg,输注的CD34^(+)细胞中位数为2.40×10^(5)/kg,脐血移植后中位随访时间98个月,44例植入成功,粒细胞和血小板植入中位时间分别为28 d和31 d,其中37例移植后植入证据检测为供者型完全嵌合,7例移植后早期检测为供受者稳定混合嵌合;(2)44例植入成功患儿中,4例发生急性移植物抗宿主病,分别为Ⅰ级(n=2)和Ⅱ级(n=2),受累器官均为皮肤,均未发生慢性移植物抗宿主病;(3)脐血移植后,48例患儿中5例发生巨细胞病毒感染及激活,12例发生败血症,3例发生侵袭性真菌病,21例发生口腔炎,8例发生出血性膀胱炎,1例发生肝静脉闭塞;(4)48例患儿中,47例存活,1例在移植后28 d因重症肺炎合并急性心力衰竭死亡,43例无病存活,3例发生原发性植入失败,1例发生移植后全血细胞减少,5年总生存率和无病生存率分别为98%和89%,1年时移植相关死亡的累计发病率为2.1%;(5)结果显示,人类白细胞抗原相合同胞新鲜脐血移植治疗儿童β重型地中海贫血的效果良好,移植物抗宿主病的发生风险低。BACKGROUND:Allogeneic hematopoietic stem cell transplantation is currently the most effective method for the radical treatment of thalassemia major,but only half of patients can find compatible bone marrow or peripheral blood stem cells.Sib-derived umbilical cord blood stem cells have different characteristics from bone marrow and peripheral blood stem cells,and are a potential alternative source of hematopoietic stem cells for transplantation in patients with thalassemia major.OBJECTIVE:To investigate the therapeutic effect of human leukocyte antigen matched sibling fresh umbilical cord blood transplantation in the treatment ofβ-thalassemia major in children.METHODS:Forty-eight children withβ-thalassemia major,including 28 males and 20 females,with a median age of 4 years old,were selected from Nanfang Hospital of Southern Medical University from June 2010 to June 2020.All of them received fresh cord blood transplantation from human leukocyte antigen matched sibling.Transplantation conditioning adopted a myeloablative regiment without anti-thymocyte globulin.A combination of cyclosporine A and mycophenolate mofetil with or without short-range methotrexate was administered for graft-versus-host disease.RESULTS AND CONCLUSION:(1)The median infused doses of total nucleated cells and CD34^(+)cells were 8.17×10^(7)/kg and 2.40×10^(5)/kg,respectively in 48 children.The median follow-up time after cord blood transplantation was 98 months,and 44 cases were successfully engrafted.The median time to neutrophil and platelet engraftment was 28 and 31 days,respectively.Among them,37 cases were found to be donor-type complete chimerism detected as evidence of implantation after transplantation,7 cases were found to be stable mixed chimerism.(2)Among the 44 children with successful implantation,four patients developed acute graft-versus-host disease,and were scored as grade I(n=2)and grade II(n=2).All the affected organs were skin,and no chronic graft-versus-host disease occurred.(3)After umbilical cord blood transplantati

关 键 词：异基因造血干细胞移植 新鲜脐血移植 β重型地中海贫血 移植物抗宿主病 儿童 

分 类 号：R457.1[医药卫生—治疗学] R319[医药卫生—临床医学] R725.5