Immunodeficiencies better treated by transplantation.
The correction of immunodeficiency requires T-cells, B-cells and antigen-presenting cells, all cooperating with each other in a balanced manner, and able to protect the tissues of the host from intracellular viral infections. Full B-cell function may require more than one genetic haplotype, and has only been achieved between host and donor cells when these are very well matched. Otherwise it has been necessary for the donor T- and B-cells to displace the host B-cells. In infants, displacement is better achieved using Busulphan rather than irradiation, (which also impairs the tolerising influence of the host thymus). Full correction has been achieved in 4 kinds of lymphopaenic SCID (+/- reticular dysgenesis or cartilage-hair dysplasia) without induction. For 16 other errors of lymphocyte function, displacement induction is preferred to ensure donor T-B-cell cooperation, although Cyclophosphamide alone has worked for matched sibling donors. For 9 other defects all expressed in phagocytes, which nevertheless occupy bone marrow space, displacement induction is essential. Elective transplants into fit hosts (e.g. no bronchiectasis) from matched sibling donors enabled 74 of 75 patients to leave hospital alive and well, with only 1 fatal acute GvHD. Currently, experienced teams can therefore consider another 20 diseases which might be better treated by bone marrow transplantation from matched siblings. In contrast, emergency transplants into unfit recipients produce only 60% survival. Transplants from donors sharing one genetic haplotype have reached 50% survival and there is room for improvement, but they are preferred to the use of unrelated donors or foetal tissues.
D001402:B-Lymphocytes / Q000276:immunology; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000276:immunology; D005333:Fetus / Q000276:immunology; D006238:Haploidy; D006650:Histocompatibility Testing; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis / Q000628:therapy*; D008099:Liver / Q000276:immunology; D016031:Liver Transplantation; D007959:Lymphocyte Culture Test, Mixed; D012801:Sibling Relations; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D014019:Tissue Donors; D014180:Transplantation / Q000379:methods
D003520:Cyclophosphamide; D002066:Busulfan