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Human leukocyte antigen (HLA) allele and haplotype frequency distribution varies widely between different ethnicities and geographical areas. Matching for HLA alleles is essential for successful related and unrelated stem cell transplantation. Among the Saudi population, data on HLA alleles and haplotypes are limited. A cross-sectional study was performed on 28,927 bone marrow donors. The most frequent HLA alleles were HLA-A*02:01:01G (20.2%), A*24:02:01G (7.5%); B*51:01:01G (19.0%), B*50:01:01G (12.3%); C*06:02:01G (16.7%), C*07:02:01G (12.2%); DRB1*07:01:01 (15.7%), DRB1*03:01:01G (13.3%); DQB1*02:01:01G (29.9%), DQB1*03:02:01G (13.2%); and DPB1*04:01:01G (35.2%), DPB1*02:01:02G (21.8%). The most frequent HLA-A~C~B~DRB1~DQB1 haplotypes were A*02:01:01G~C*06:02:01G~B*50:01:01G~DRB1*07:01:01G~DQB1*02:01:01G (1.9%) and A*02:05:01G~C*06:02:01G~B*50:01:01G~DRB1*07:01:01G~DQB1*02:01:01G (1.6%). The most frequent HLA-A~C~B~DRB1~DQB1~DPB1 haplotypes were A*02:01:01G~C*15:02:01G~B*51:01:01G~DRB1*04:02~DQB1*03:02:01G~DPB1*04:01:0G (1%) and A*02:01:01G~C*07:02:01G~B*07:02:01G~DRB1*15:01:01G~DQB1*06:02:01G~ DPB1*04:01:01G (0.9%). Based on these haplotype frequencies, we provide forecasts for the fraction of patients with full matching and single mismatched donors for 3 to 6 loci depending on the registry size. With one million donors, about 50% of the patients would find an 8/8 match and 90% a 7/8 match. These data are essential for registry planning, finding unrelated stem cell donors, population genetic studies, and HLA disease associations.

The degree of HLA concordance with the patient has long been known to be the major donor-related prediction factor for the success of hematopoietic stem cell transplantations and, with the progress of HLA typing technology, selection criteria became more stringent with regard to the recommended loci and resolution. A late refinement was HLA-C matching, which gained broader acceptance only after the turn of the millennium. The enormous HLA polymorphism has always necessitated registries with a large number of donors in order to be able to provide well-matched donors to a substantial fraction of patients. Using a biostatistical approach, we investigated the impact of adding HLA-C at low or high resolution as a supplementary matching criterion on some key parameters in donor provision for a European-Caucasian population. Starting point is donor selection based on allele level matching for HLA-A, -B, -DRB1, and, optionally, HLA-DQB1. Without typing for HLA-C, 68% of the donors selected based on matching for HLA-A, -B, -DRB1, and -DQB1 at high resolution will also match for HLA-C, 29% will have a single and only 3% will have two HLA-C alleles different from the patient. In order to provide the same fraction of patients with a fully matched donor, a registry would have to be about twice the size if HLA-C is considered in addition to the four other loci, with the exact factor increasing with the registry’s size. If the provision of donors with up to a single allele mismatch is considered, this factor doubles due to the strong linkage between HLA-B and -C. These figures only change slightly when HLA-DQB1 is completely ignored or HLA-C matching is only considered at low resolution. Our results contribute to quantifying the medical and economic impact of the progress in donor selection algorithms.

The activation of antigen specific T cells by tumor associated antigens (TAA) might be a promising treatment strategy for patients with renal cell carcinoma (RCC). We analyzed TAA expression in patients with RCC as well as the prevalence of fitting HLA phenotypes and calculated the percent of patients eligible for peptide vaccination trials.A total of 41 RCC samples from primary tumors were analyzed for TAA expression by reverse transcriptase-polymerase chain reaction. Genes of interest were MAGE-1, MAGE-3, G250 and PRAME since peptides derived from these genes have been shown to activate antigen specific cytotoxic T lymphocytes. Results were combined with data on the HLA gene and haplotype frequencies in the German population as an example of a white population.Tumor specific expression of at least 1 T-cell activating antigen was observed in all patients. Of the patients 80% expressed 2 or more TAAs simultaneously. HLA molecules suitable for presentation of the respective antigens were calculated to be expressed in 51% to 85% of white German patients. These results mirror with only minor variations most of the white populations in Europe and North America.We noted that T-cell activating tumor associated antigens are frequently expressed in patients with RCC. Based on HLA expression analysis in a white population at least 30% of patients with RCC are eligible for monovalent specific immunotherapy and 41% are eligible for polyvalent specific immunotherapy. These data are a rational basis for future prospective vaccination trials in patients with RCC.

The majority of patients which are eligible for a blood stem cell transplantation from an allogeneic donor do not have a suitable related donor so that an efficient unrelated donor search is a prerequisite for this treatment. Currently, there are over 7 million volunteer donors in the files of 50 registries in the world and in most countries the majority of transplants are performed from a foreign donor. Evidently, computer and communication technology must play a crucial role in the complex donor search process on the national and international level. This article describes the structural elements of the donor search process and discusses major systematic and technical issues to be addressed in the development and evolution of the supporting telematic systems. The theoretical considerations are complemented by a concise overview over the current state of the art which is given by describing the scope, relevance, interconnection and technical background of three major national and international computer appliances: The German Marrow Donor Information System (GERMIS) and the European Marrow Donor Information System (EMDIS) are interoperable business-to-business e-commerce systems and Bone Marrow Donors World Wide (BMDW) is the basic international donor information desk on the web.