异基因造血干细胞移植治疗X-连锁肾上腺脑白质营养不良患儿的临床研究  

Clinical study of allogeneic hematopoietic stem cell transplantation for children with X-linked adrenoleukodystrophy

作　　者：翟宗 胡绍燕[1] 王易[1] 李捷[1] 卢俊[1] 肖佩芳[1] 凌婧[1] 胡昳歆 高莉 Zhai Zong;Hu Shaoyan;Wang Yi;Li Jie;Lu Jun;Xiao Peifang;Ling Jing;Hu Yixin;Gao Li(Department of Hematology and Oncology,Children′s Hospital of Soochow University,Suzhou 215000,Jiangsu Province,China)

机构地区：[1]苏州大学附属儿童医院血液肿瘤科,215000

出　　处：《国际输血及血液学杂志》2020年第4期325-331,共7页International Journal of Blood Transfusion and Hematology

基　　金：江苏省妇幼健康科研项目(F201815);苏州市"科教兴卫"青年科技项目(KJXW2019024);苏州市科技计划项目(SS2019065)。

摘　　要：目的探讨X-连锁肾上腺脑白质营养不良(X-ALD)患儿的临床特点,以及接受异基因造血干细胞移植(allo-HSCT)的疗效。方法选择2015年2月至2018年12月,苏州大学附属儿童医院收治的3例X-ALD患儿为研究对象。这3例患儿按照入院时间先后顺序依次编号为患儿1、2、3;均为男性,年龄分别为7岁6个月、9岁7个月、8岁10个月;均伴脑型肾上腺脑白质营养不良(CALD)症状。采集其一般临床资料;均接受改良氟达拉滨+白消安+环磷酰胺预处理方案,2例接受双份脐血移植(UCBT),1例为单倍体造血干细胞移植(haplo-HSCT)。采取回顾性分析方法,分析这3例X-ALD患儿的临床特征及allo-HSCT疗效,对其随访截至2019年12月31日。本研究遵循的程序符合2013年修订版《世界医学协会赫尔辛基宣言》的要求。结果①入院时,患儿1头颅MRI检查结果提示双侧顶枕叶白质、胼胝体压部、脑干部分纵行纤维受累;神经功能评分为0分,Loes评分为8分。患儿2头颅MRI检查结果提示中脑外侧、2侧背侧丘脑后部、胼胝体压部等处受累;神经功能评分为0分,Loes评分为15分。患儿3头颅MRI检查结果提示双侧大脑脚及颞顶枕叶受累;入院时已发生失语,癫痫发作,双下肢、左上肢肌张力明显升高;神经功能评分为8分,Loes评分为6分。3例患儿均符合X-ALD诊断,其中患儿2、3按照神经功能和Loes评分不适宜接受allo-HSCT,而患儿家长仍强烈要求对患儿采取移植治疗。②接受预处理方案后,全部患儿allo-HSCT成功。患儿1、2、3输注的单个核细胞计数分别为0.74×10^8/kg、0.73×10^8/kg、2.22×10^8/kg;CD34+细胞计数分别为0.26×10^6/kg、0.32×10^6/kg、2.27×10^6/kg;中性粒细胞植入时间分别为移植后第20、12、9天,血小板植入时间分别为移植后第43、14、11天,3例患儿均植入成功。③随访结果显示,患儿1的短阵串联重复序列(STR)监测结果提示为完全植入状态,未发生移植物抗宿�Objective To investigate characteristics of children with X-linked adrenoleukodystrophy(X-ALD)and the effect of allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods From February 2015 to December 2018,a total of 3 children with X-ALD admitted to the Children′s Hospital of Soochow University were selected as the research subjects.According to the order of admission time,3 cases were numbered as child 1,2 and 3.They were all male.Their ages were 7 years and 6 months,9 years and 7 months,8 years and 10 months,respectively.All the 3 cases were accompanied with cerebral adrenoleukodystrophy(CALD)symptoms.Clinical data of 3 cases with X-ALD were collected.All the children were pretreated with modified fludarabine+busulfan+cyclophosphamide regimen.Child 1,2 received double umbilical cord blood transplantation(UCBT)and child 3 received haploidentical hematopoietic stem cell transplantation(haplo-HSCT).Clinical features and the curative effect of allo-HSCT in children with X-ALD were retrospectively analyzed.The procedure followed in this study was in accordance with the requirements of the World Medical Association Declaration of Helsinki revised in 2013.Results①After admitted,head MRI examination of child 1 showed that the white matter of bilateral parietal occipital lobe,splenium of corpus callosum and part of brainstem were involved.Neurological function score was 0 and Loes score was 8.Head MRI of child 2 showed that the lateral midbrain,bilateral dorsal thalamus and splenium callosum were involved.Neurological function score was 0 and Loes score was 15.Head MRI showed bilateral cerebral peduncle and temporal parietal occipital lobe involvement in child 3.The child had aphasia and epileptic seizures when he was admitted to hospital.The muscle tension of both lower limbs and left upper limbs was significantly increased.Neurological function score was 8 and Loes score was 6.All of the 3 children were diagnosed as X-ALD.Child 2 and 3 were not suitable for allo-HSCT according to above scores,but thei

关 键 词：造血干细胞移植 肾上腺脑白质营养不良 神经系统 移植物抗宿主病 儿童 

分 类 号：R725.9[医药卫生—儿科]