脐带血干细胞移植治疗异染性脑白质营养不良3例报告

doi:10.12372/jcp.2024.22e1424

摘要/Abstract

摘要：

目的探讨脐带血造血干细胞移植（UCBT）治疗异染性脑白质营养不良（MLD）的安全性及有效性。方法回顾性分析2019年4月至9月行非血缘UCBT治疗的3例MLD患儿的临床资料。结果 3例患儿均表现为走路障碍、进行性运动功能倒退，2例出现智力落后；3例均出现溶酶体芳基硫酸脂酶A（ARSA）下降，头部MRI均示脑白质不同程度的异常信号。3例均为ARSA基因复合杂合突变。3例均行非血缘UCBT，使用氟达拉滨+环磷酰胺+兔抗人胸腺细胞免疫球蛋白+白消安方案预处理，环孢素+吗替麦考酚酯+甲氨蝶呤预防移植物抗宿主病（GVHD）。3例均植入成功，移植后1个月内全血均达到完全供者嵌合状态，头部MRI均提示脑实质病变逐渐停止进展，ARSA均逐渐恢复正常。3例患儿均出现感染，2例出现急性移植物抗宿主反应（aGVHD），1例出现慢性移植物抗宿主反应（cGVHD），经抗感染及调节免疫治疗后均好转。末次随访时间为2022年8月，3例患儿均存活，其远期疗效及神经系统恢复情况仍需长期随访。结论 UCBT是阻止MLD进展的一种安全及有效治疗手段。

关键词: 脐带血, 造血干细胞移植, 异染性脑白质营养不良

Abstract:

Objective To investigate the safety and efficacy of umbilical cord blood transplantation (UCBT) in the treatment of metachromatic leukodystrophy (MLD). Methods The clinical data of 3 MLD children treated with unrelated UCBT from April to September 2019 were retrospectively analyzed. Results All the 3 children showed walking disorder, progressive motor function regression, and 2 of them showed mental retardation. Lysosomal arylsulfatase A (ARSA) decreased in all of them. Head MRI of all the 3 children showed abnormal signals of different degrees in the white matter of the brain and they all had compound heterozygous mutations of ARSA gene. All the 3 children were treated with unrelated UCBT, and the pre-treatment regimen was fludarabine + cyclophosphamide + rabbit anti-human thymocyte immunoglobulin + busulfan, and the prevention of graft-versus-host disease (GVHD) was treated with cyclosporine + mycophenolate mofetil + methotrexate. All the 3 children were successfully implanted, and the whole blood of all children reached complete donor chimerism within 1 month after transplantation. Head MRI showed that the progression of brain parenchymal lesions gradually stopped, and ARSA levels gradually returned to normal. All 3 patients developed infection, 2 developed acute GVHD and 1 developed chronic GVHD. After anti-infection and regulatory immunotherapy, they all improved. The last follow-up was in August 2022, and all 3 patients survived. Long-term efficacy and neurological recovery still require long-term follow-up.Conclusion UCBT is a safe and effective treatment to prevent the progression of MLD.

Key words: umbilical cord blood, hematopoietic stem cell transplantation, metachromatic leukodystrophy

管丽蔷, 姜帆, 陈姣, 刘周阳, 孙媛. 脐带血干细胞移植治疗异染性脑白质营养不良3例报告[J]. 临床儿科杂志, 2024, 42(3): 249-252.

GUAN Liqiang, JIANG Fan, CHEN Jiao, LIU Zhouyang, SUN Yuan. Umbilical cord blood transplantation in the treatment of metachromatic leukodystrophy: a report of 3 cases[J]. Journal of Clinical Pediatrics, 2024, 42(3): 249-252.

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患儿	性别	发病年龄	类型	首发症状	智力评估	ARSA /nmol·17h^-1·mg^-1	头部MRI
例1	男	1岁6个月	晚婴型	走路障碍	>85.0分	8.2	胼胝体压部T2W1及压水序列信号稍增高
例2	男	1岁2个月	晚婴型	左眼斜视、走路姿势异常、不能独立行走	83.0分	4.8	1.双侧半卵圆中心及双侧侧脑室周围脑白质异常信号；2.双侧额颞部脑外间隙增宽；3.DTI序列测得双侧内囊前肢、双侧内囊后肢、胼胝体压部、胼胝体膝部脑白质区FA值，均低于同龄儿童正常范围，提示脑白质髓鞘化进程缓慢
例3	女	5岁	少年型	腹痛，发热、抽搐、走路姿势异常	66.4分（轻度发育迟缓）	6.3	双侧额顶叶白质，胼胝体区可见对称片状长T1、T2信号，FLAIR成高信号，DWI胼胝体区，双侧额叶呈点调状高信号