• Cerebral adrenoleukodystrophy manifests as progressive inflammatory demyelination leading to neurological function loss and early death.

  • Early allo-HSCT stabilizes CALD progression; transplant-related morbidity remains high, even with improved regimens and supportive care.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in early cerebral adrenoleukodystrophy (CALD) can stabilize neurologic function and improve survival but has associated risks including transplant related mortality (TRM), graft failure, and graft-versus-host disease (GVHD). An observational study of 59 patients with median age at allo-HSCT of 8 years addressed impact of donor source, donor match, conditioning regimen, and cerebral disease stage on first allo-HSCT outcomes. Efficacy analyses included 53 patients stratified by disease category: advanced disease (AD; n=16) with Loes score >9 or neurological function score (NFS) >1 and two early disease (ED) cohorts (ED1 [Loes ≤4 and NFS ≤1; n=24] and ED2 [Loes >4-9 and NFS ≤1; n=13]). Survival free of major functional disabilities and without second allo-HSCT at 4 years was significantly higher in the ED (66%) versus AD (41%) cohort (p=0.015) and comparable between ED1 and ED2 cohorts (p=0.991). The stabilization of neurologic function post-transplant was greater in the ED versus AD cohort, with a median change from baseline at 24 months post-allo-HSCT in NFS and Loes score, respectively, of 0 and 0.5 in ED1 (n=13), 0.5 and 0 in ED2 (n=6), and 2.5 and 3.0 (n=4) in AD cohort. TRM was lower in the ED (7%) compared with AD (22%) cohort, however the difference was not significant (p=0.094). Transplant-related safety outcomes were also impacted by transplant-related characteristics: graft failure incidence was significantly higher with unrelated umbilical cord grafts versus matched related donors (MRD) (p=0.039), and acute GVHD and graft failure incidences varied by conditioning regimen. The study is registered to https://clinicaltrials.gov as NCT02204904.

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