Variables affecting outcomes after allogeneic hematopoietic stem cell transplant for cerebral adrenoleukodystrophy.

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in early cerebral adrenoleukodystrophy 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 2 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%) vs AD (41%) cohort (P = .015) and comparable between ED1 and ED2 cohorts (P = .991). The stabilization of neurologic function posttransplant was greater in the ED vs AD cohort, with a median change from baseline at 24 months after 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 the AD (22%) cohort; however, the difference was not significant (P = .094). Transplant-related safety outcomes were also affected by transplant-related characteristics: graft failure incidence was significantly higher with unrelated umbilical cord grafts vs matched related donors (P = .039), and acute GVHD and graft failure incidences varied by conditioning regimen. This study was registered at www://clinicaltrials.gov as #NCT02204904.

• Authors: Robert Chiesa, Jaap Jan Boelens, Christine N Duncan, Jörn-Sven Kühl, Caroline Sevin, Neena Kapoor, Vinod K Prasad, Caroline A Lindemans, Simon A Jones, Hernan M Amartino, Mattia Algeri, Nancy Bunin, Cristina Diaz-de-Heredia, Daniel J Loes, Esther Shamir, Alison Timm, Elizabeth McNeil, Andrew C Dietz, Paul J Orchard
• Journal: Blood advances (Blood Adv) Vol. 6 Issue 5 Pg. 1512-1524 (03 08 2022) ISSN: 2473-9537 [Electronic] United States
• PMID: 34781360 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Topics

• Adrenoleukodystrophy (therapy)
• Graft vs Host Disease (etiology)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Recurrence
• Transplantation Conditioning (adverse effects)