Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999.
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.
Peters
Charles
C
Department of Pediatrics, University of Minnesota, Minneapolis, USA. peter392@umn.edu
Charnas
Lawrence R
LR
Tan
Ye
Y
Ziegler
Richard S
RS
Shapiro
Elsa G
EG
DeFor
Todd
T
Grewal
Satkiran S
SS
Orchard
Paul J
PJ
Abel
Susan L
SL
Goldman
Anne I
AI
Ramsay
Norma K C
NK
Dusenbery
Kathryn E
KE
Loes
Daniel J
DJ
Lockman
Lawrence A
LA
Kato
Shunichi
S
Aubourg
Patrick R
PR
Moser
Hugo W
HW
Krivit
William
W
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
D007166:Immunosuppressive Agents