Efficacy of hematopoietic cell therapy in X-linked adrenoleukodystrophy: a multinstitutional study (ALD-101). G. Raymond1, P. Orchard2, P. Aubourg3, M. Escolar4, J. Kurtzberg5, S. Paadre6, J. Balser6 1) Department of Neurology, University of Minnesota, Minneapolis, MN; 2) Department of Pediatrics, University of Minnesota, Minneapolis, MN; 3) University Paris Descartes, Paris France; 4) Program for the Study of Neurodevelopment in Rare Diseases, Children's Hospital of Pittsburgh, Pittsburgh, PA; 5) Pediatric Blood & Marrow Transplant Program, Duke University Medical Center, Durham, N.C; 6) Veristat, Holliston, MA.

   Objective: The only therapy for childhood cerebral adrenoleukodystrophy (CCALD) is hematopoietic cell therapy (HCT), but there is limited outcome information compared to untreated boys. Methods: We conducted a retrospective study (ALD-101) to characterize subjects with untreated CCALD and collect efficacy and safety data from HCT treated boys. Data was collected on 136 cases (72 untreated/ 65 HCT) from diagnosis till either 2 years post-diagnosis or death from 5 centers, 4 in the US and 1 in France. Established measures of neurologic function (NFS) and MRI (Loes) were used in all cases. Results: In the untreated, 70 of 72 (97%) had at least one NFS score and an MRI; 30 (42%) with gadolinium (23 Gad+/7Gad-). Enhancement was highly predictive of rapid progression. Of the Gad+, 19 had more than one NFS score recorded and the majority showed significant decline in 6-18 months and no resolution of enhancement in the untreated group. In the 65 HCT-treated boys, all were evaluated with NFS and MRI with contrast. In the treated cohort there was resolution of enhancement (median 3.4 months) and stabilization of MRI and NFS. Engraftment failure occurred in 18.5% and the rate of severe acute and chronic GVHD was 11% and 5% respectively. The highest incidence of death occurred in those boys undergoing an HLA mismatched , non related transplant (12/32; 37.5%). Conclusions: We report here the largest retrospective, multi-institutional study of untreated and treated CCALD, demonstrating that MRI enhancement is predictive of progression, and that it rapidly resolves following HCT. Successful HCT improved all measures of disease.

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