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.