Outcomes of an optimized ciclosporin-free haploidentical HSCT protocol in paediatric patients with cerebral adrenoleukodystrophy.

Haploidentical haematopoietic stem cell transplantation (haplo-HSCT) expands donor availability for cerebral adrenoleukodystrophy (cALD). However, conventional graft-versus-host disease (GVHD) prophylaxis based on calcineurin inhibitors like ciclosporin (CsA) poses a potential neurotoxicity risk that may exacerbate neurological injury. We retrospectively analysed 26 cALD patients who underwent haplo-HSCT with an optimized ciclosporin-free GVHD prophylaxis regimen consisting of anti-thymocyte globulin (ATG; 4 mg/kg), post-transplant cyclophosphamide (PTCy) and mycophenolate mofetil. Neutrophil and platelet engraftment each occurred at a median of 15 days (ranges, 13-26 and 9-33 days respectively). The cumulative incidence (CI) of grades II-IV acute GVHD by day 100 was 18.49% ± 8.37%, and the 3-year CI of moderate-to-severe chronic GVHD was 9.32% ± 6.28%. After a median follow-up of 29 months, overall survival was 90.4% ± 6.6% and major functional disability-free survival was 69.0% ± 9.1%. Post-transplantation, plasma C26:0 levels and the C24:0/C22:0 and C26:0/C22:0 ratios were markedly reduced. Magnetic resonance imaging (MRI) at a mean of 7.3 ± 5.9 months post-HSCT showed largely preserved LOES scores without significant progression. Our experience supports the safety and efficacy of this optimized ciclosporin-free haplo-HSCT approach for patients with cALD, warranting further validation in prospective studies.