title: 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.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, USA. peter392@umn.edu
authors.forename: Charles
authors.initials: C
authors.lastname: Peters
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Charnas
authors.forename: Ye
authors.initials: Y
authors.lastname: Tan
authors.forename: Richard S
authors.initials: RS
authors.lastname: Ziegler
authors.forename: Elsa G
authors.initials: EG
authors.lastname: Shapiro
authors.forename: Todd
authors.initials: T
authors.lastname: DeFor
authors.forename: Satkiran S
authors.initials: SS
authors.lastname: Grewal
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
authors.forename: Susan L
authors.initials: SL
authors.lastname: Abel
authors.forename: Anne I
authors.initials: AI
authors.lastname: Goldman
authors.forename: Norma K C
authors.initials: NK
authors.lastname: Ramsay
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Dusenbery
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Loes
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Lockman
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kato
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Aubourg
authors.forename: Hugo W
authors.initials: HW
authors.lastname: Moser
authors.forename: William
authors.initials: W
authors.lastname: Krivit
mesh_terms: D000326:Adrenoleukodystrophy / Q000401:mortality / Q000628:therapy*; D002423:Cause of Death; D018450:Disease Progression; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000401:mortality / Q000706:statistics & numerical data*; D016019:Survival Analysis; D013997:Time Factors; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome; D014916:Whole-Body Irradiation
chemical_list: D007166:Immunosuppressive Agents