Peters Charles, Charnas Lawrence R, Tan Ye, Ziegler Richard S, Shapiro Elsa G, DeFor Todd, Grewal Satkiran S, Orchard Paul J, Abel Susan L, Goldman Anne I, Ramsay Norma K C, Dusenbery Kathryn E, Loes Daniel J, Lockman Lawrence A, Kato Shunichi, Aubourg Patrick R, Moser Hugo W, Krivit William
Department of Pediatrics, University of Minnesota, Minneapolis, USA.
Blood. 2004 Aug 1;104(3):881-8. doi: 10.1182/blood-2003-10-3402. Epub 2004 Apr 8.
Cerebral X-linked adrenoleukodystrophy (X-ALD) is a disorder of very-long-chain fatty acid metabolism, adrenal insufficiency, and cerebral demyelination. Death occurs within 2 to 5 years of clinical onset without hematopoietic cell transplantation (HCT). One hundred twenty-six boys with X-ALD received HCT from 1982 to 1999. Survival, engraftment, and acute graft-versus-host disease were studied. Degree of disability associated with neurologic and neuropsychological function and cerebral demyelination were evaluated before and after HCT. Complete data were available and analyzed for 94 boys with cerebral X-ALD. The estimated 5- and 8-year survival was 56%. The leading cause of death was disease progression. Donor-derived engraftment occurred in 86% of patients. Demyelination involved parietal-occipital lobes in 90%, leading to visual and auditory processing deficits in many boys. Overall 5-year survival of 92% in patients with 0 or 1 neurologic deficits and magnetic resonance imaging (MRI) severity score less than 9 before HCT was superior to survival for all others (45%; P <.01). Baseline neurologic and neuropsychological function, degree of disability, and neuroradiologic status predicted outcomes following HCT. In this first comprehensive report of the international HCT experience for X-ALD, we conclude that boys with early-stage disease benefit from HCT, whereas boys with advanced disease may be candidates for experimental therapies.
脑性X连锁肾上腺脑白质营养不良(X-ALD)是一种极长链脂肪酸代谢紊乱、肾上腺功能不全和脑脱髓鞘疾病。未经造血细胞移植(HCT),患者在临床发病后2至5年内死亡。1982年至1999年,126名患有X-ALD的男孩接受了HCT。研究了生存率、植入情况和急性移植物抗宿主病。在HCT前后评估了与神经和神经心理功能以及脑脱髓鞘相关的残疾程度。对94名患有脑性X-ALD的男孩进行了完整数据的分析。估计5年和8年生存率为56%。主要死亡原因是疾病进展。86%的患者发生了供体来源的植入。90%的患者脱髓鞘累及顶枕叶,导致许多男孩出现视觉和听觉处理缺陷。HCT前神经功能缺损为0或1且磁共振成像(MRI)严重程度评分低于9的患者,总体5年生存率为92%,优于其他所有患者(45%;P<0.01)。基线神经和神经心理功能、残疾程度以及神经放射学状态可预测HCT后的结果。在这份关于X-ALD国际HCT经验的首次综合报告中,我们得出结论,早期疾病的男孩可从HCT中获益,而晚期疾病的男孩可能是实验性治疗的候选者。