Key Points Question What are the risks to stable neurocognitive outcome after allogeneic hematopoietic stem cell transplantation for childhood cerebral X-linked adrenoleukodystrophy? Findings This single-center case series involving 36 boys with cerebral X-linked adrenoleukodystrophy found that all patients with favorable neuroimaging and matched bone marrow transplant had stable neurocognitive survival. In contrast, the disease progressed for all patients without these factors, and many developed major functional disabilities. Meaning Patients without matched bone marrow transplant or with unfavorable neuroimaging findings may need therapeutic options other than hematopoietic stem cell transplantation.
Importance Allogeneic hematopoietic stem cell transplantation is the standard intervention for childhood cerebral X-linked adrenoleukodystrophy. However, the pretransplant conditions, demyelination patterns, complications, and neurological outcomes of this therapy are not well characterized. Objectives To identify the risks to stable neurocognitive survival after hematopoietic stem cell transplantation and to describe subgroups of patients with distinct clinical long-term outcomes. Design, Setting, and Participants This case series analyzed the treatment and outcome of a cohort of 36 boys who underwent hematopoietic stem cell transplantation at Charité Universitätsmedizin Berlin, Germany, between January 1, 1997, and October 31, 2014. Case analysis was performed from January 1, 2016, through November 30, 2017. During this retrospective review, the adrenoleukodystrophy-disability rating score and the neurological function score were used. Demyelinating lesions in the brain were quantified by the Loes score. Main Outcomes and Measures Overall survival, survival without major functional disabilities, and event-free survival were analyzed. Patients’ clinical symptoms, demyelination patterns, and stem cell source were stratified. Results Of the 36 boys who underwent hematopoietic stem cell transplantation, the median (range) age was 7.2 (4.2-15.4) years; 18 were presymptomatic and 18 were symptomatic. Twenty-seven patients (75%) were alive at a median (interquartile range [IQR]) follow-up of 108 (40-157) months. Sixteen of 18 presymptomatic patients (89%) survived, and 13 (72%) had an event-free survival with a median (IQR) survival time of 49 (37-115) months. Among the symptomatic patients, 11 of 18 (61%) survived, but only 1 was an event-free survival (6%) (median [IQR] time, 9 [3-22] months). Of the 9 patients who received a bone marrow transplant from a matched family donor, all survived. Among the 36 patients, 6 disease-related deaths (17%) and 3 transplant-related deaths (8%) occurred. Deaths from disease progression (n = 6) occurred only in patients with demyelination patterns other than parieto-occipital. In total, 18 patients (50%) displayed limited parieto-occipital (Loes score
This case series examines the factors that contribute to disease progression and neurological deterioration in children who undergo hematopoietic stem cell transplantation to treat cerebral X-linked adrenoleukodystrophy.