Use of donors sharing one genetic haplotype for bone marrow transplantation.
Matched sibling transplants enjoy over 95% survival of the grafting procedure, but are only available for 1:5 patients. A sibling sharing one genetic haplotype is today our next choice of donor (67% survival) faring better than other relatives (50% survival), providing total body irradiation (of the thymus) has been avoided. The latter, without increasing the attack rate (64%) of GvHD more than doubles the deaths (57% as against 27%) attributable to it. Rejection is avoided by (a) suicide of host responders to donor buffy coat; (b) Cyclosporin-A; (c) displacement induction; (d) a higher dose of marrow. Prevention of GvHD is essential, using either Cyclosporin-A or removing donor T-cells from marrow prior to infusion or, probably better, both. Autoblast immunisation should be further explored. Tolerization seems an active process, easier in the very young, and nonirradiation of the thymus is believed important. An assay to assess tolerization (to guide cessation of immunosuppressive measures) is badly needed. Selection of a donor whose lymphocytes can deal with intracellular infections of the host's fibroblasts is now possible. The required increased immunosuppressive measures appear to increase the risk of leukemic relapse, and perhaps should be first improved in the more cost-effective fields of inborn error transplants.
D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D003524:Cyclosporins / Q000627:therapeutic use; D004306:Dose-Response Relationship, Immunologic; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000401:mortality; D006238:Haploidy; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000532:radiotherapy; D008222:Lymphokines / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology / Q000502:physiology; D013997:Time Factors; D014019:Tissue Donors
D003524:Cyclosporins; D008222:Lymphokines; D003520:Cyclophosphamide; D002066:Busulfan