Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Juvenile Metachromatic Leukodystrophy Compared With Nontransplanted Control Patients
Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Juvenile Metachromatic Leukodystrophy Compared With Nontransplanted Control Patients
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DOI：
10.1001/jamaneurol.2016.2067
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发表时间：
2016-09-01
期刊：
影响因子：
29
通讯作者：
Mueller, Ingo
中科院分区：
文献类型：
--
作者：
Groeschel, Samuel;Kuehl, Joern-Sven;Mueller, Ingo
重要性 同种异体造血干细胞移植 (HSCT) 是过去 20 年来临床上可用于治疗青少年异染性脑白质营养不良 (MLD) 的唯一治疗选择，据报道，结果各异，且未与疾病的自然病程进行比较。 目的 比较接受同种异体 HSCT 的患者与未接受青少年 MLD 队列的对照患者的长期结果。受试者 1975 年至 2009 年出生的青少年 MLD 患者，中位年龄为 7 岁（年龄范围 1.5-18.2 岁）接受 HSCT 的患者，以及 1967 年至 2007 年出生的青少年 MLD 的非移植患者均纳入本病例对照研究。 HSCT 后的中位随访时间为 7.5 年（范围：3.0-19.7 年）。患者于 1991 年至 2012 年间在 3 个德国中心接受了 HSCT。分析于 2014 年 7 月至 2015 年 8 月期间进行。 主要结果和指标 生存率和移植相关死亡率、粗大运动功能丧失（MLD 中的粗大运动功能分类）、任何语言功能丧失以及脑部变化的磁共振成像 (MRI) 严重程度评分。为了探讨基线时的预后因素，根据粗大运动和认知功能，将接受 HSCT 的患者（以下称为移植患者）预先分为稳定型与进展型疾病。 结果 参与者为 24 名移植患者（11 名男孩，13 名女孩）和 41 名未接受移植的青少年 MLD 患者（以下称非移植患者）（22 名男孩，19 名女孩）。在移植患者中，4 名儿童死于移植相关死亡，另外 2 名儿童在 HSCT 后 1.5 和 8.6 年死于 MLD 快速进展，导致 5 年生存率为 79%（24 名儿童中的 19 名）。在未接受移植的患者中，发病后 5 年生存率为 100%（41 例中的 41 例）。然而，有 11 人死于 MLD 进展，观察期内总体生存率相似。 HSCT 后的长期幸存者中有 9 名出现疾病进展，而 11 名则表现出疾病稳定。与非移植患者相比，移植患者丧失粗大运动或语言功能的可能性较小，并且在最近一次检查中表现出明显较低的 MRI 严重程度评分。当早期接受 HSCT 时，当发病年龄大于 4 岁或 MRI 严重程度评分较低时（最好是
IMPORTANCE Allogeneic hematopoietic stem cell transplantation (HSCT) has been the only treatment option clinically available during the last 20 years for juvenile metachromatic leukodystrophy (MLD), reported with variable outcome and without comparison with the natural course of the disease.OBJECTIVE To compare the long-term outcome of patients who underwent allogeneic HSCT with control patients who did not among a cohort with juvenile MLD.DESIGN, SETTING, AND PARTICIPANTS Patients with juvenile MLD born between 1975 and 2009 and who received HSCT at a median age of 7 years (age range, 1.5-18.2 years) and nontransplanted patients with juvenile MLD born between 1967 and 2007 were included in this case-control study. The median follow-up after HSCT was 7.5 years (range, 3.0-19.7 years). Patients underwent HSCT at 3 German centers between 1991 and 2012. The analysis was done between July 2014 and August 2015.MAIN OUTCOMES AND MEASURES Survival and transplantation-related mortality, loss of gross motor function (Gross Motor Function Classification in MLD), loss of any language function, and magnetic resonance imaging (MRI) severity score for cerebral changes. To explore prognostic factors at baseline, patients who underwent HSCT (hereafter, transplanted patients) were a priori divided into stable vs progressive disease, according to gross motor and cognitive function.RESULTS Participants were 24 transplanted patients (11 boys, 13 girls) and 41 control patients (22 boys, 19 girls) who did not receive transplantation (hereafter, nontransplanted patients) with juvenile MLD. Among the transplanted patients, 4 children died of transplantation-related mortality, and 2 additional children died of rapid MLD progression 1.5 and 8.6 years after HSCT, resulting in a 5-year survival of 79% (19 of 24). Among the nontransplanted patients, 5-year survival after disease onset was 100% (41 of 41). However, 11 died of MLD progression, resulting in similar overall survival within the observation period. Nine of the long-term survivors after HSCT had disease progression, while 11 showed stable disease. Compared with the nontransplanted patients, the transplanted patients were less likely to lose their gross motor or language function and demonstrated significantly lower MRI severity scores at the latest examination. Patients after HSCT were more likely to have a stable disease course when undergoing HSCT at an early stage with no or only mild gross motor deficits (Gross Motor Function Classification in MLD level 0 or 1) and an IQ of at least 85, when age at disease onset was older than 4 years, or when MRI severity scores were low (preferably