Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999

Abstract

Cerebral X-linked adrenoleukodystrophy (X-ALD) is a disorder of very-long-chain fatty acid metabolism, adrenal insufficiency, and cerebral demyelination. Death occurs within 2 to 5 years of clinical onset without hematopoietic cell transplantation (HCT). One hundred twenty-six boys with X-ALD received HCT from 1982 to 1999. Survival, engraftment, and acute graft-versus-host disease were studied. Degree of disability associated with neurologic and neuropsychological function and cerebral demyelination were evaluated before and after HCT. Complete data were available and analyzed for 94 boys with cerebral X-ALD. The estimated 5-and 8-year survival was 56%. The leading cause of death was disease progression. Donor-derived engraftment occurred in 86% of patients. Demyelination involved parietal-occipital lobes in 90%, leading to visual and auditory processing deficits in many boys. Overall 5-year survival of 92% in patients with 0 or 1 neurologic deficits and magnetic resonance imaging (MRI) severity score less than 9 before HCT was superior to survival for all others (45%; P < .01). Baseline neurologic and neuropsychological function, degree of disability, and neuroradiologic status predicted outcomes following HCT. In this first comprehensive report of the international HCT experience for X-ALD, we conclude that boys with early-stage disease benefit from HCT, whereas boys with advanced disease may be candidates for experimental therapies. (Blood. 2004;104: 881-888)

Umbilical cord blood banking: an update

“…In the past 25 years, nearly a thousand patients with metabolic storage disorders have received allogeneic hematopoietic stem cell transplantation for curative purposes using bone marrow from HLA-matched or mismatched related donors. This results in clinical benefit by replacing the missing enzyme produced by the donor cells circulating in the blood [39][40][41][42][43].…”

Efficient correction of Fabry mice and patient cells mediated by lentiviral transduction of hematopoietic stem/progenitor cells

“…7,8 In general, outcomes have been long-term but only partly effective. There are two major reasons limiting the clinical application of allogeneic SCT.…”

N-acetyl-L-cysteine improves outcome of advanced cerebral adrenoleukodystrophy

“…Overall, the 5-year survival of patients with a Loes MRI severity score of o9 before HSCT is 92%, versus 45% for patients who have a severity score of 49 and have more than one neurologic deficit. 8 As a result of the increased risk of death after HSCT, transplant is not currently recommended for individuals with advanced disease. Unfortunately, there are no other current treatment alternatives.…”