造血干细胞移植治疗重型β-地中海贫血合并难治性自身免疫性溶血性贫血一例报告并文献复习  

Hematopoietic stem cell transplantation in the treatment ofβ-thalassemia major complicated by refractory autoimmune hemolytic anemia:A case report and literature review

作　　者：吴小燕 张相梅 潘洪鑫 黄佩 谭梅 杜作晨 何志旭 陈艳 Wu Xiaoyan;Zhang Xiangmei;Pan Hongxin;Huang Pei;Tan Mei;Du Zuochen;He Zhixu;Chen Yan(Department of Pediatrics,Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou 563099,China;Collaborative Innovation Center for Tissue Injury Repair and Regenerative Medicine Guizhou Children′s Hospital,Zunyi Guizhou 563099,China)

机构地区：[1]贵州省儿童医院,遵义医科大学附属医院小儿内科,贵州遵义563099 [2]遵义医科大学组织损伤修复与再生医学省部共建协同创新中心,贵州遵义563099

出　　处：《遵义医科大学学报》2023年第1期88-92,共5页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:82260036);省部共建协同创新中心项目(NO:教科技厅函[2020]39);贵州省科技计划项目(NO:黔科合平台人才-CXTD[2021]010)。

摘　　要：目的探讨造血干细胞移植治疗重型β-地中海贫血合并难治性自身免疫性溶血性贫血治疗效果。方法回顾2020年12月28日贵州省儿童医院1例重型β-地中海贫血(β41-42纯合突变)合并难治性自身免疫性溶血性贫血患儿行亲缘性HLA全相合造血干细胞移植的案例,分析其临床特征,并通过检索“难治性自身免疫性溶血/refractory autoimmune hemolytic anemia”、“造血干细胞移植/hematopoietic stem cell transplantation”为关键词检索维普数据库、万方数据库、中国知网数据库及PubMed、Web of Science数据库自建库至2022年6月收录的文献,分析治疗效果。结果8岁女患,7年前因面色苍白起病,就诊于海南某三甲医院完善地贫基因,提示β41-42纯合突变,明确诊断重型β-地中海贫血;2年前患儿因反复出现皮肤巩膜黄染、浓茶色尿,查血红蛋白最低至22 g/L,网织红细胞6.3%,直接抗人球蛋白实验阳性,故诊断自身免疫性溶血性贫血。2020年12月28日,经家属知情同意后,行亲缘性HLA全相合造血干细胞移植(HSCs),供者为其同胞哥哥。患儿HLA-Ⅰ、Ⅱ类混合抗体强阳性,本次入院前已予血浆置换清除抗体治疗。移植预处理方案:氟达拉滨、白消安、环磷酰胺及抗人胸腺细胞免疫球蛋白;预防移植物抗宿主病方案:环孢素、甲氨蝶呤及吗替麦考酚酯,排除造血干细胞移植禁忌;经右侧颈内静脉输注供者外周血干细胞(MNC 6.19×10^(8)/kg,CD34^(+)6.85×10^(6)/kg)输注,14 d后患儿造血及免疫功能重建。外送嵌合检查提示:外周血中供者细胞占比99.55%;移植后随访患儿血常规未见异常,脱离输血。结论异基因造血干细胞移植可以同时治愈儿童重型地中海贫血和合并的难治性自身免疫性溶血性贫血。Objective To investigate the efficacy of hematopoietic stem cell transplantation(HSCT)forβ-thalassemia major complicated with refractory autoimmune hemolytic anemia.Methods A case ofβ-thalassemia major(β41-42 homozygous mutation)complicated by refractory autoimmune hemolytic anemia treated by HSCT in Guizhou Children′s Hospital on December 282020 was retrospectively analyzed.The clinical characteristics were summarized,and literature searched by key words of"refractory autoimmune hemolytic anemia and hematopoietic stem cell transplantation"in VIP database,Wanfang database,CNKI database,PubMed and Web of Science from the day they were founded to June 2022.Results The 8-year-old female patient,who was hospitalized to a tertiary hospital in Hainan province for pale complexion 7 years ago,and diagnosed withβ-thalassemia major due to a homozygous mutation ofβ41-42 by gene test.Two years ago,the patient was further diagnosed with autoimmune hemolytic anemia with repeated yellowing of the skin and sclera,thick brown urine,low hemoglobin level(22 g/L),high reticulocyte ratio(6.3%),and positive direct antiglobulin test.On December 282020,after taking informed consent,the patient was treated with allogeneic HLA HSCT with her older sibling donor's HLA-identical peripheral blood hematopoietic stem cells(HSCs).Because of the mixed HLA-Ⅰ and Ⅱ antibody test of the patient was strongly positive,plasma exchange was performed before HSCT.The regimens used for pre-treatment are fludarabine,busulfan,cyclophosphamide and anti-thymocyte globulin.The regimens used for prophylaxis Graft-Versus-Host-Disease are cyclosporin,methotrexate,and mycophenolate mofetil.The donor′s peripheral blood stem cells(MNC 6.19×10^(8)/kg,CD34^(+)6.85×10^(6)/kg)were infused via the right jugular vein,14 days after,the patient’s hematopoietic and immune function were reconstructed,and the implantation rate reached 99.55%in peripheral blood.After transplantation,the children did not need blood transfusion any more,and no obvious abnormality

关 键 词：难治性自身免疫性溶血性贫血 重型Β-地中海贫血 造血干细胞移植 

分 类 号：R725.5[医药卫生—儿科]