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The development of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka and colleagues in 2006 has led to a potential new paradigm in cellular therapeutics, including the possibility of producing patient-specific, disease-specific and immune matched allogeneic cell therapies. One can envisage two routes to immunologically compatible iPSC therapies: using genetic modification to generate a ‘universal donor’ with reduced expression of Human Leukocyte Antigens (HLA) and other immunological targets or developing a haplobank containing iPSC lines specifically selected to provide HLA matched products to large portions of the population. HLA matched lines can be stored in a designated physical or virtual global bank termed a ‘haplobank’. The process of ‘iPSC haplobanking’ refers to the banking of iPSC cell lines, selected to be homozygous for different HLA haplotypes, from which therapeutic products can be derived and matched immunologically to patient populations.By matching iPSC and derived products to a patient’s HLA class I and II molecules, one would hope to significantly reduce the risk of immune rejection and the use of immunosuppressive medication. Immunosuppressive drugs are used in several conditions (including autoimmune disease and in transplantation procedures) to reduce rejection of infused cells, or transplanted tissue and organs, due to major and minor histocompatibility differences between donor and recipient. Such regimens can lead to immune compromise and pathological consequences such as opportunistic infections or malignancies due to decreased cancer immune surveillance. In this article, we will discuss what is practically involved if one is developing and executing an iPSC haplobanking strategy.

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.

We investigated a possible interaction between age-associated risk and HLA-mismatch associated risk on prognosis in different age categories of recipients of unrelated hematopoietic stem cell transplants (HSCT) (n=3019). Patients over 55 years of age transplanted with 8/10 donors showed a mortality risk of 2.27 (CI 1.70–3.03, P

The diversity of the human leukocyte antigen (HLA) class I and II alleles can be simplified by consolidating them into fewer supertypes based on functional or predicted structural similarities in epitope-binding grooves of HLA molecules. We studied the impact of matched and mismatched HLA-A (265 versus 429), -B (230 versus 92), -C (365 versus 349), and -DRB1 (153 versus 51) supertypes on clinical outcomes of 1934 patients with acute leukemias or myelodysplasia/myeloproliferative disorders. All patients were reported to the Center for International Blood and Marrow Transplant Research following single-allele mismatched unrelated donor myeloablative conditioning hematopoietic cell transplantation. Single mismatched alleles were categorized into six HLA-A (A01, A01A03, A01A24, A02, A03, A24), six HLA-B (B07, B08, B27, B44, B58, B62), two HLA-C (C1, C2), and five HLA-DRB1 (DR1, DR3, DR4, DR5, DR9) supertypes. Supertype B mismatch was associated with increased risk of grade II–IV acute graft-versus-host disease (hazard ratio =1.78, P=0.0025) compared to supertype B match. Supertype B07-B44 mismatch was associated with a higher incidence of both grade II–IV (hazard ratio=3.11, P=0.002) and III–IV (hazard ratio=3.15, P=0.01) acute graft-versus-host disease. No significant associations were detected between supertype-matched versus -mismatched groups at other HLA loci. These data suggest that avoiding HLA-B supertype mismatches can mitigate the risk of grade II–IV acute graft-versus-host disease in 7/8-mismatched unrelated donor hematopoietic cell transplantation when multiple HLA-B supertype-matched donors are available. Future studies are needed to define the mechanisms by which supertype mismatching affects outcomes after alternative donor hematopoietic cell transplantation.