脐带血干细胞移植治疗异染性脑白质营养不良3例报告

Umbilical cord blood transplantation in the treatment of metachromatic leukodystrophy:a report of 3 cases

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(c GVHD),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。

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.