Allogeneic Stem Cell Transplant for Cerebral Adrenoleukodystrophy: The Changing Role of Alternative Donors.

BACKGROUND

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a key therapy for stabilizing neurological function and improving survival in cerebral adrenoleukodystrophy (CALD). Identifying a suitable matched related donor (MRD) or unrelated donor remains challenging, especially in countries with limited donor registry representation. These barriers have increased the use of alternative donors, such as haploidentical or umbilical cord blood grafts. Early transplantation is associated with better outcomes.

METHODS

We describe outcomes of seven consecutive children with rapidly progressive CALD who underwent allo-HSCT between January 2015 and December 2023 at a single institution in Colombia, including matched related donor and alternative donors (haploidentical related and umbilical cord blood). Clinical data, imaging, and transplant characteristics were collected retrospectively.

RESULTS

Seven children underwent allo-HSCT at a median age of 8 years. The median (range) age at CALD diagnosis was 8 years (4-11), and the median interval from CALD diagnosis to allo-HSCT was 14 months (range, 6-36). Alternative donors were used in six of seven cases (86%). Neutrophil engraftment occurred in six patients (85%) at a median of 15 days (12-29), and platelet engraftment in all evaluable patients at a median of 18 days (12-27). The median follow-up duration after transplant was 24 months. Two patients experienced stable or preserved neurological function, while others showed progression or died from transplant or disease-related complications.

CONCLUSIONS

This study highlights real-world outcomes of allo-HSCT for CALD in a resource-limited setting. The findings underscore the importance of early diagnosis and expedited donor access to optimize neurological outcomes.