Ten years' experience of bone marrow transplantation for Gaucher disease.

Six patients underwent allogeneic bone marrow transplantation (BMT) because of severe Gaucher disease. Their ages was from 2 to 9 years at the time of transplantation. The donors were 4 HLA-identical siblings, a father with one incompatible HLA antigen and an HLA-A, -B, and -DR-identical unrelated donor. Among the donors, three were heterozygous for glucocerebrosidase and three were healthy homozygotes. Four patients underwent total splenectomy and two patients partial splenectomy prior to transplantation. In the former group one patient developed pneumococcal meningitis. In the latter group transfusion requirements were increased. The parental graft was rejected, but 4 of 5 other patients have donor enzyme levels from 2 up to 11 years after BMT. Two patients became mixed chimeras with around 40% of donor erythrocyte markers for one and 80% for the other. One of these had low enzyme activity in his lymphocytes, but the clinical outcome is excellent. This case gives good hope for future trials with gene therapy in Gaucher disease. Glucosylceramide in plasma was within the normal range in all other patients with engraftment, but glucosylceramide in erythrocytes were in the upper normal range in the two chimeric patients with heterozygous donors. Glucosylceramide levels in the liver decreased markedly in the two patients where it was studied. Gaucher cells disappeared in the bone marrow and liver size normalized or decreased within two to three years after BMT. All patients with engraftment had a growth spurt. Skeletal kyphosis was unaffected by BMT in three patients and became apparent in one patient 8 years after BMT. The patients had a favorable psychological development after BMT, with an excellent IQ between 112 and 120 ten years after BMT in the longest survivor. The data suggest that in advanced Gaucher disease BMT still may be a treatment of choice if an HLA-identical related or unrelated donor is available.