BONE MARROW TRANSPLANTATION (BMT) IN GAUCHER??S DISEASE:

A 19 year-old female with non-neuronopathic Gaucher's Disease had 3 BMT's from 2 partially HLA-matched, carrier, sibling donors. Pre-BMT glucocerebrosidase (glc-ase) activity in leukocytes and liver were 13 and 9% of controls respectively. BMT #1 was done in 8/81 (donor=brother) after fractionated total lymphoid irradiation (100 rad × 18). Donor leukocytes (XY) were found in the blood (1-3%) for 6 weeks and in marrow (6-9%) for 3 months with no graft vs. host disease. A 2nd BMT (same donor) failed and graft cells disappeared. Leukocyte glc-ase activity never changed. During 1982 the patient developed marrow failure. In 2/83, using a sister as donor, she had a 3rd BMT after cyclophosphamide (120 mg/kg), total body x-ray (165 rad × 8) and cyclosporine. She engrafted promptly and had normal or supranormal leukocyte glc-ase levels by day +27 and thereafter. At death on day +50 from cyclosporine toxicity (capillary leak syndrome) and polymicrobial sepsis, her bone marrow showed partial clearing of Gaucher cells. Her liver had increased its glc-ase levels from 1.7 to 4.7 U/mg protein ([3H]-glucocerebroside substrate; 25% normal). The brain had very low enzyme levels (12% normal). Conclusion: BMT offers the Gaucher patient effective enzyme replacement for cells of marrow origin in the circulation and in reticuloendothelial organs. Whether remissions of clinical disease will occur and glc-ase levels in the CNS will rise after BMT remains to be determined.