目的:伴有神经系统受累的肾上腺脑白质营养不良(ALD)的预后通常是令人沮丧的;然而,异基因干细胞移植(SCT)被认为是稳定或改善ALD临床症状的有效方法。在这里,我们报告了ALD患者的临床结局,这些患者在我们的机构连续接受了同种异体干细胞移植并降低了预处理强度.
方法:16例ALD患者,有症状(n=14)或症状前(n=2),2010年至2016年收到SCT。干细胞来源为脐带血(n=14),或来自相同同胞的人类白细胞抗原的骨髓(n=2)。移植前的预处理方案强度降低,由氟达拉滨(125mg/m2)组成,美法仑(140mg/m2)和4Gy(n=15)或3Gy(n=1)的低剂量全身照射(TBI)。
结果:在11例患者中获得了一次植入,5例失去初次移植物的患者中有4例接受了第二次脐带血移植并进行了移植。5年总生存率和无事件生存率分别为90.9%和61.1%。中位数为45个月(范围16-91)。除内囊受累患者外,Loes评分在移植后18个月稳定或改善。
结论:对ALD患者进行强度降低的同种异体SCT是安全的,即使在有症状的患者中也没有重大的移植相关并发症,对无内囊受累的患者进行SCT后神经系统症状稳定。
OBJECTIVE: The prognosis of adrenoleukodystrophy (ALD)with neurological involvement is generally dismal; however, allogeneic stem cell transplantation (SCT) is recognized as effective to stabilize or improve the clinical symptoms of ALD. Herein, we report the clinical outcomes of patients with ALD who consecutively underwent allogeneic stem cell transplantation with reduced intensity conditioning at our institution.
METHODS: Sixteen patients with ALD, who were symptomatic (n = 14) or presymptomatic (n = 2), received SCT from 2010 to 2016. The stem cell source was cord blood (n = 14), or bone marrow from a human leukocyte antigen identical sibling (n = 2). The conditioning regimen prior to transplantation was reduced intensity and consisted of fludarabine (125 mg/m2), melphalan (140 mg/m2) and low dose total body irradiation (TBI) of 4Gy (n = 15) or 3Gy (n = 1).
RESULTS: Primary engraftment was obtained in 11 patients, and 4 of the 5 patients who lost the primary graft received a second cord blood transplantation and were engrafted. Five years overall and event-free survival were 90.9% and 61.1% respectively, with a median of 45 months (range 16-91). Loes score stabilized or improved by 18 months after transplantation except for patients with internal capsule involvement.
CONCLUSIONS: Allogeneic SCT with reduced intensity conditioning for patients with ALD was safely performed without major transplant-related complications even in symptomatic patients and neurological symptoms were stabilized after SCT in patients without internal capsule involvement.