HCT is the only currently available therapy for CCALD, but there is limited multi-institutional outcome data.

We conducted a retrospective study to characterize the natural history of untreated CCALD and the efficacy and safety of HCT. Data were collected from 5 centers, 4 in US and 1 in France on 136 cases (72 untreated/65 HCT) from diagnosis until either 2 years post-diagnosis or death. Key efficacy measures were neurologic-function-score (NFS) and MRI (Loes).

In the untreated, 70 of 72 (97%) had at least one NFS score and an MRI; 31 (43%) with gadolinium (24 Gad+/7Gad-). Gadolinium enhancement was highly predictive of rapid progression. Of the Gad+, the majority showed significant decline in NFS and Loes scores during the follow-up period. In the 65 HCT-treated boys, all were evaluated with NFS and MRI with contrast. Majority (93%) had resolution of enhancement (median 3.4 months). In a subset of 22 HCT-treated patients with early CCALD (NFS ≤ 1, Loes ≤ 9), 73% had stabilization of NFS (NFS≤ 4 or change in NFS≤3) at 24 months post-transplant. Engraftment failure occurred in 18.5%, and severe acute and chronic GVHD in 11% and 5%, respectively. The highest incidence of death during the follow-up period occurred in HLA mismatched, non-related transplants (12/32; 37.5%)  These subjects also had the highest incidence of overall (23/32,72%) and serious GVHD (6/32,19%).

MRI enhancement is predictive of progression, and it rapidly resolves following HCT. Successful HCT improved all outcomes versus untreated. There is a clear unmet need for novel therapies for patients without an HLA-matched sibling donor.