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.

The use of short tandem repeat polymorphisms for monitoring chimerism following bone marrow transplantation: a short report.

Following immunohaematopoietic stem cell transplantation, it is of importance to determine whether the new blood forming system is of recipient or donor origin and such phenotypic characterisation is called chimerism analysis. This is a dynamic process, which may be complete, mixed or split between compartments and in this way, plays an increasingly important role in predicting outcome for engraftment, rejection or residual disease predicating the need for pre-emptive immunotherapy. Based on recent workshop recommendations, peripheral blood cells have been used in the short tandem repeat (STR) assay to serially characterise the haematologic course and so evaluate the usefulness of this system. Forty-six patients from a single centre were followed serially for periods ranging between 3 and 60 months. The analysis was initially performed using the Applied Biosystems Profiler Plus Kit; currently, the Promega Powerplex 16 system is used. The overlap between the two assays has allowed for continuous comparison. The initial analysis was performed at 14 days post-transplant and repeated monthly. Stored DNA from the patient and donor was used to establish the pre-transplant profile. All post-transplant analyses were performed using peripheral blood. The results obtained were expressed as a percentage of the donor profile. To illustrate the ability of this technology, three representative profiles are described. In the first, stable engraftment is confirmed at 20 months with only donor pattern present. The second is intermediate, and while the patient is clinically disease free, there exists stable mixed chimerism at about 75% of donor cells. The third patient initially engrafted but the reappearance of recipient alleles presaged a haematological relapse; the latter is an indication for salvage with donor lymphocyte infusion and here this assay will be used to show the effectiveness of the intervention. These preliminary results show this to be a useful additional tool in monitoring post-transplant engraftment. As a basis for pro-active therapy, a larger study integrating the results of haematological and cytogenetic markers is planned.

The South African bone marrow registry (SABMR) in 2004.

Because of the presence of rare HLA antigens, particularly in patients of African ancestry, the SABMR was established in 1991. Currently approximately 20% of unique HLA types in the international database is from the SABMR. The SABMR donors now total approximately 45,000. Sixty-five South African patients have received matched unrelated donor transplants, 20 (30%) with a local donor. Most donors are from Caucasian background. To increase the genetic diversity of the SABMR donor pool, the policy is now to enrol more black and mixed ancestry donors.