Bone marrow grafts in congenital deficiencies
Hobbs, J.R.; Chambers, D.J.; Williamson, S.A.; Barnes, I.; Desai, S.; Ingram, L.; Matthews, P.A.; James, D.C.; Selwyn, S.; High-Jones, K.
La Clinica Terapeutica 110(5): 409-416
1984
ISSN/ISBN: 0009-9074 PMID: 6238756 Document Number: 222771
For certain fatal inborn errors of metabolism expressed and detectable in the leukocytes, transplanted normal bone marrow can daily produce 50-300 g of leukocytes, most of which will release enzyme on their way through the tissues of the body. Sometimes such an enzyme is released in quantities adequate for pinocytosis and utilization within the accessible areas of the cytoplasm of the deficient host cells. It is important to ensure tolerance by the host against the missing enzyme or component, and in general it is best first to displace the useless host bone marrow stem cells with a course of Busulphan 80 mg/m2 daily .times. 4 or by 8 Gy [Gray] of total body irradiation (preferably avoided in infancy). The Westminster Team completed transplants in 37 patients of whom 8 were considered cured, 9 were progressing satisfactorily and 3 had chronic GVHD [graft vs. host disease] [54% survival). While the systemic manifestations of mucopolysaccharidoses were reversed and further brain damage seems to be arrested, it was still too early to know whether normal mental function will eventually result. Some grafts experienced late rejection, and cyclosporin-A had a narrow therapeutic range in infants, but currently, grafts from normal compatible siblings can expect 90% survivors; from mismatched donors sharing a genetic haplotype, 65%; from unrelated matched donors, 40%.