The South African Bone Marrow Registry (SABMR) and allogeneic bone marrow transplantation

In 1939 Osgood et al. reported infusing bone marrow into patients with severe aplastic anaemia without any clinical benefit. Rekers and Coulter attempted to reconstitute marrow function in irradiated dogs by marrow infusions. Both failed because of insufficient irradiation to produce immunosuppression necessary for engraftment. In 1957 Donnall Thomas and co-workers showed that marrow can be collected, stored in significant quantities and safely administered. Marrow transplants remained unsuccessful, however, although patients with refractory leukaemia given supralethal irradiation recovered after marrow infusion from identical twins. Allogeneic marrow transplants usually resulted in failed engraftment, or engraftment followed by lethal graft-versus-host disease (GVHD). Further discoveries were the HLA complex and transplantation antigens, and that successful allogeneic engrafting depends upon donor/recipient histocompatibility

Investigations of the Genetic aspects of the mixed Lymphocyte culture reaction in Southern Africa

The genetic relationship between the serologically detectable antigens of the HLA-A and B loci and the mixed lymphocyte culture (MLC) reaction is of utmost importance in the understanding of histocompatibility. From the literature it appeared that neither the HLA-A, B genotype nor the MLC reaction is the complete answer to donorrecipient selection in organ transplantation. This study was therefore initiated in June 1971 in an attempt to clarify the problem. It is inherent in a project of this nature that much time is spent in collecting samples from donors in diverse areas. Most experiments had to be repeated two or three times, therefore some of the problems we set out to resolve were clarified by other workers before we were able to complete our investigations

HLA-C expression levels define permissible mismatches in hematopoietic cell transplantation

Life-threatening graft-versus-host disease (GVHD) limits the use of HLA-C-mismatched unrelated donors in transplantation. Clinicians lack criteria for donor selection when HLA-C-mismatched donors are a patient's only option for cure. We examined the role for HLA-C expression levels to identify permissible HLA-C mismatches. The median fluorescence intensity, a proxy of HLA-C expression, was assigned to each HLA-C allotype in 1975 patients and their HLA-C-mismatched unrelated transplant donors. The association of outcome with the level of expression of patients' and donors' HLA-C allotypes was evaluated in multivariable models. Increasing expression level of the patient's mismatched HLA-C allotype was associated with increased risks of grades III to IV acute GVHD, nonrelapse mortality, and mortality. Increasing expression level among HLA-C mismatches with residue 116 or residue 77/80 mismatching was associated with increased nonrelapse mortality. The immunogenicity of HLA-C mismatches in unrelated donor transplantation is influenced by the expression level of the patient's mismatched HLA-C allotype. HLA-C expression levels provide new information on mismatches that should be avoided and extend understanding of HLA-C-mediated immune responses in human disease