HEMATOPOIETIC STEM-CELL TRANSPLANTATION IN GLOBOID-CELL LEUKODYSTROPHY

Background Globoid-cell leukodystrophy is caused by a deficiency of ga lactocerebrosidase, which results in progressive central nervous syste m deterioration. We investigated whether allogeneic hematopoietic stem -cell transplantation can provide a source of leukocyte galactocerebro sidase and thereby prevent the decline of central nervous system funct ion in patients with the disease. Methods Five children with globoid-c ell leukodystrophy (one with the infantile type and four with late-ons et disease) were treated with allogeneic hematopoietic stem-cell trans plantation. Measurement of leukocyte galactocerebrosidase levels, neur ologic examinations, neuropsychological tests, magnetic resonance imag ing of the central nervous system, cerebrospinal fluid protein assays, and neurophysiologic measurements were performed before and after tra nsplantation, with follow-up ranging from one to nine years. Results E ngraftment of donor-derived hematopoietic cells occurred in all patien ts and was followed by restoration of normal leukocyte galactocerebros idase levels. In the four patients with late-onset disease, the centra l nervous system deterioration was reversed, and in the patient with t he infantile form of the disease, signs and symptoms have not appeared . Magnetic resonance imaging showed a decrease in signal intensity in the three patients with late-onset disease who were assessed both befo re and after transplantation. Abnormalities in cerebro spinal fluid to tal protein levels were corrected in three patients with late-onset di sease and substantially reduced in the patient with the infantile form . Conclusions Central nervous system manifestations of globoid-cell le ukodystrophy can be reversed by allogeneic hematopoietic stem-cell tra nsplantation. (C) 1998, Massachusetts Medical Society.