Department of Pediatric Oncology/Hematology/SCT, Charité Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
Department of Hematology, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.
Brain. 2017 Apr 1;140(4):953-966. doi: 10.1093/brain/awx016.
The adult cerebral inflammatory form of X-linked adrenoleukodystrophy is a rapidly progressive neurodegenerative disease, as devastating as childhood cerebral adrenoleukodystrophy. Allogeneic haematopoietic stem cell transplantation has been demonstrated to provide long-term neurological benefits for boys with the childhood cerebral form, but results in adults are sparse and inconclusive. We analysed data from 14 adult males with adult cerebral adrenoleukodystrophy treated with allogeneic haematopoietic stem cell transplantation on a compassionate basis in four European centres. All presented with cerebral demyelinating lesions and gadolinium enhancement. Median age at diagnosis of adult cerebral adrenoleukodystrophy was 33 years (range 21-48 years). In addition to cerebral inflammation, five patients had established severe motor disability from adrenomyeloneuropathy affecting only the spinal cord and peripheral nerves (Expanded Disability Status Scale score ≥ 6). Eight patients survived (estimated survival 57 ± 13%) with a median follow-up of 65 months (minimum 38 months). Death was directly transplant-/infection-related (n = 3), due to primary disease progression in advanced adult cerebral adrenoleukodystrophy (n = 1), or secondary disease progression (n = 2) after transient multi-organ failure or non-engraftment. Specific complications during stem cell transplantation included deterioration of motor and bladder functions (n = 12) as well as behavioural changes (n = 8). Arrest of progressive cerebral demyelination and prevention of severe loss of neurocognition was achieved in all eight survivors, but deterioration of motor function occurred in the majority (n = 5). Limited motor dysfunction (Expanded Disability Status Scale score < 6) prior to transplantation was associated with significantly improved survival [78 ± 14% (n = 9) versus 20 ± 18%(n = 5); P < 0.05] and maintenance of ambulation (Expanded Disability Status Scale score < 7) post-transplant (78% versus 0%; P = 0.021). In contrast, bilateral involvement of the internal capsule on brain MRI was associated with poorer survival [20 ± 18% (n = 5) versus 78 ± 14% (n = 9); P < 0.05]. This study is the first to support the feasibility, complications and potential long-term neurological benefit of allogeneic haematopoietic stem cell transplantation in adult cerebral adrenoleukodystrophy. Further studies are warranted to attempt to improve outcomes through patient selection and optimization of transplantation protocols.
X 连锁肾上腺脑白质营养不良的成人脑炎性形式是一种快速进展性神经退行性疾病，与儿童脑型肾上腺脑白质营养不良一样具有破坏性。同种异体造血干细胞移植已被证明可为儿童脑型提供长期神经益处，但在成人中的结果稀少且不确定。我们分析了在四个欧洲中心以同情为基础接受同种异体造血干细胞移植治疗的 14 名患有成人脑肾上腺脑白质营养不良的成年男性的数据。所有患者均表现为脑脱髓鞘病变和钆增强。成人脑肾上腺脑白质营养不良的诊断中位年龄为 33 岁（范围 21-48 岁）。除脑炎症外，5 名患者还因仅影响脊髓和周围神经的肾上腺脑脊髓神经病而患有严重的运动残疾（扩展残疾状况量表评分≥6）。8 名患者存活（估计存活率 57±13%），中位随访时间为 65 个月（最小 38 个月）。死亡直接与移植/感染有关（n=3），原因是晚期成人脑肾上腺脑白质营养不良的原发性疾病进展（n=1），或在短暂的多器官衰竭或非植入后发生继发性疾病进展（n=2）。干细胞移植期间的具体并发症包括运动和膀胱功能恶化（n=12）以及行为改变（n=8）。所有 8 名幸存者均实现了进行性脑脱髓鞘的停止和神经认知严重丧失的预防，但大多数患者（n=5）的运动功能恶化。移植前存在有限的运动功能障碍（扩展残疾状况量表评分<6）与显著改善的存活率相关[78±14%（n=9）与 20±18%（n=5）；P<0.05]和移植后保持步行能力（扩展残疾状况量表评分<7）（78%与 0%；P=0.021）。相比之下，脑 MRI 上内囊的双侧受累与较差的存活率相关[20±18%（n=5）与 78±14%（n=9）；P<0.05]。这项研究首次支持在成人脑肾上腺脑白质营养不良中进行同种异体造血干细胞移植的可行性、并发症和潜在的长期神经益处。需要进一步的研究来尝试通过患者选择和移植方案的优化来改善结果。
