Allogenic bone marrow transplantation in severe gaucher disease

Philip Tsai, Jeffrey M. Lipton, Indira Sahdev, Vesna Najfeld, Linda R. Rankin, Arnold H. Slyper, Mark Ludman, Gregory A. Grabowski

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


Gaucher disease is the most prevalent lysosomal storage disease. This autosomal recessive disease is caused by the defective activity of the enzyme acid 0-glucosidase and the resultant accumulation of glucosylcer-amide primarily within cells of the reticuloendothelial system. Because the primary manifestations of Gaucher disease are due to involvement of monocyte/macrophage-derived cells, this disease is thought to be an excellent candidate for curative intervention via bone marrow transplantation (BMT). A Hispanic female with subacute neu-ronopathic Gaucher disease and rapidly progressing visceral manifestations underwent BMT at 23 mo of age using her histocompatible normal brother as the donor. Cytogenetic analyses demonstrated complete, stable engraftment by 1 mo post-BMT. During the subsequent 24 mo, clinical, biochemical, enzymatic, and histologic studies demonstrated nearly complete correction in the viscera. Her neuropathic manifestations did not progress. Complete re-constitution of enzymatic activity in peripheral blood leukocytes was achieved by 1 mo. Cytogenetic analyses demonstrated complete engraftment by d 79 and nearly complete loss of bone marrow Gaucher cells was observed by 8 mo. Plasma glucosylceramide levels normalized by 8-12 mo. Nearly coincident improvements in hepatic size, enzyme levels, and histology were found by 12-24 mo post-BMT. Fatal sepsis occurred at 24 mo post-BMT. Autopsy revealed sparse Gaucher cells in clusters in the liver, lymph nodes, and lungs as well as the lack of periadventitial Gaucher cells surrounding brain vessels. The findings provide the time course and rationale for studies directed to gene therapy via BMT for this disease after introduction of acid β-glucosidase gene constructs into autologous plu-ripotent stem cells of selected Gaucher disease patients.

Original languageEnglish
Pages (from-to)503-507
Number of pages5
JournalPediatric Research
Issue number5
StatePublished - May 1992


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