非亲缘脐带血干细胞移植治疗CD40配体基因突变引起的高IgM综合征三例并文献复习  

Unrelated umbilical cord blood stem cell transplantation in the treatment of hyper-IgM syndrome caused by CD40 ligand gene mutation:a report of three cases and literature review

作　　者：王苹 钱晓文 王宏胜 江文晋 孙金峤[2] 王晓川[2] 翟晓文 Wang Ping;Qian Xiaowen;Wang Hongsheng;Jiang Wenjin;Sun Jinqiao;Wang Xiaochuan;Zhai Xiaowen(Department of Hematology,Children′s Hospital of Fudan University,National Children′s Medical Center,Shanghai 201102,China;Department of Immunology,Children′s Hospital of Fudan University,National Children′s Medical Center,Shanghai 201102,China)

机构地区：[1]国家儿童医学中心,复旦大学附属儿科医院血液科,上海201102 [2]国家儿童医学中心,复旦大学附属儿科医院免疫科,上海201102

出　　处：《中华儿科杂志》2021年第10期830-835,共6页Chinese Journal of Pediatrics

摘　　要：目的评价减低强度预处理非亲缘脐带血干细胞移植(UCBT)治疗CD40配体基因(CD40LG)突变引起的高IgM综合征(HIGM)的有效性及安全性。方法回顾性分析2018年5月至2019年8月复旦大学附属儿科医院收治的由CD40LG突变引起的3例HIGM患儿的临床特征、实验室资料和UCBT治疗的预后。以“CD40配体基因”“造血干细胞移植”“CD40 ligand deficiency”“hematopoietic stem cell transplantation”为关键词在万方数据库、中国知网、维普数据库及PubMed数据库中检索建库至2021年2月的文献,总结该病的移植供者选择、干细胞来源、预处理方案及预后因素。结果3例男性患儿均以反复呼吸道感染起病,基因检测均为CD40LG突变。3例患儿移植前年龄分别为1.0、1.4及0.5岁,均采用白消安、氟达拉滨及环磷酰胺的减低强度预处理方案。脐带血干细胞与患儿人类白细胞抗原相合度分别为8/10、10/10及9/10。3例患儿在移植后14 d均达到完全供者细胞嵌合,均发生了Ⅰ度皮肤急性移植物抗宿主病,无其他严重并发症发生。截至末次随访,3例患儿分别为移植后33、18及18个月,均无病生存。文献检索到中文文献0篇,英文文献24篇。文献报道共258例CD40LG突变的患儿行造血干细胞移植(HSCT)治疗,供者类型以同胞相合供者[30.6%(79/258)]及非亲缘相合供者[40.3%(104/258)]为主,干细胞来源以骨髓[50.8%(131/258)]为主,预处理方案以清髓性预处理[66.7%(172/258)]为主,移植后总体生存率为70.9%(183/258),移植前存在肺损伤、肝脏并发症是影响患儿预后的不良因素。14例UCBT患儿中2例植入失败、2例混合嵌合、3例移植后死亡。结论UCBT治疗CD40LG突变引起的HIGM安全有效,减低强度预处理方案值得进一步研究。Objective To evaluate the efficacy and safety of unrelated umbilical cord blood stem cell transplantation(UCBT)with reduced-intensity conditioning regimens in the treatment of hyper-IgM syndrome(HIGM)caused by CD40 ligand gene(CD40LG)mutation.Methods Clinical features,laboratory data and treatment prognosis of 3 patients with HIGM caused by CD40LG mutation treated with UCBT in Children′s Hospital of Fudan University from May 2018 to August 2019 were analyzed retrospectively.The literature search was conducted with"CD40 ligand deficiency"and"hematopoietic stem cell transplantation"as keywords at China National Knowledge Infrastructure,Wanfang,Weipu and Pubmed databases(up to February 2021)to summarize donor selection,stem cell source,conditioning regimen and prognostic factors of this disease.Results Three boys with recurrent respiratory tract infection were diagnosed as HIGM with CD40LG mutation.The age of UCBT was 1.0,1.4 and 0.5 years respectively.Reduced-intensity conditioning regimen including busulifan,fludarabine and cyclophosphamide were used in all patients.Human leucocyte antigen matching of patients and umbilical cord blood was 8/10,10/10 and 9/10 respectively.All patients achieved complete donor chimerism 14 days after UCBT.All patient suffered gradeⅠacute skin graft-versus-host disease without other severe complications.Up to the last follow-up,their disease-free survival time were 33,18,18 months after transplantation respectively.No reports were found in Chinese journals,while 24 publications were found in English journals.According to the literature,258 HIGM patients with CD40LG mutation were treated with hematopoietic stem cell transplantation(HSCT).Matched sibling donors(30.6%(79/258))and unrelated donors(40.3%(104/258))were main donor types.Bone marrow(50.8%(131/258))was the main source of grafts,myeloablative conditioning(66.7%(172/258))was the main conditioning regimen,and the overall survival rate after transplantation was 70.9%(183/258).Lung injury and liver complications before transpla

关 键 词：CD40配体 脐血干细胞移植 回顾性研究 

分 类 号：R725.9[医药卫生—儿科] R457.7[医药卫生—临床医学]