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Supporting allogeneic hematopoietic cell transplantation (HCT) is an integral function of the clinical HLA laboratory, which provides HLA testing for recipients and donors. However, the timing, scope, and methods of the HLA tests vary significantly in the field. This summary provides a comprehensive and practical HLA testing approach to maximize the efficiency of the donor search process, minimize donor-specific HLA antibody (DSA) associated risks, enable optimal donor selections, and support HCT multidisciplinary teams. This is not a comprehensive donor selection guide, but pertinent donor selection considerations and publicly available online selection tools are highlighted. In the absence of healthy HLA identical siblings, younger 8/8 (HLA-A, -B, -C, -DRB1) HLA-matched unrelated donors remain the most favorable choice for HCT. Emerging practices in preparative regimens and graft versus host disease (GvHD) prophylaxis as well as building evidence of the importance of other HLA (e.g., HLA-DPB1 allele and functional matching) and non-HLA (e.g., age, CMV, and KIR) donor attributes urge the transplant centers and the HLA laboratories to construct a comprehensive approach for the routine histocompatibility testing.

In this study, we investigated HLA class I and class II allele and haplotype frequencies in Emiratis and compared them to those of Asian, Mediterranean, and Sub-Saharan African populations. Methods: Two-hundred unrelated Emirati parents of patients selected for bone marrow transplantation were genotyped for HLA class I (A, B, C) and class II (DRB1, DQB1) genes using reverse sequence specific oligonucleotide bead-based multiplexing. HLA haplotypes were assigned with certainty by segregation (pedigree) analysis, and haplotype frequencies were obtained by direct counting. HLA class I and class II frequencies in Emiratis were compared to data from other populations using standard genetic distances (SGD), Neighbor-Joining (NJ) phylogenetic dendrograms, and correspondence analysis. Results: The studied HLA loci were in Hardy–Weinberg Equilibrium. We identified 17 HLA-A, 28 HLA-B, 14 HLA-C, 13 HLA-DRB1, and 5 HLA-DQB1 alleles, of which HLA-A*02 (22.2%), -B*51 (19.5%), -C*07 (20.0%), -DRB1*03 (22.2%), and -DQB1*02 (32.8%) were the most frequent allele lineages. DRB1*03~DQB1*02 (21.2%), DRB1*16~DQB1*05 (17.3%), B*35~C*04 (11.7%), B*08~DRB1*03 (9.7%), A*02~B*51 (7.5%), and A*26~C*07~B*08~DRB1*03~DQB1*02 (4.2%) were the most frequent two- and five-locus HLA haplotypes. Correspondence analysis and dendrograms showed that Emiratis were clustered with the Arabian Peninsula populations (Saudis, Omanis and Kuwaitis), West Mediterranean populations (North Africans, Iberians) and Pakistanis, but were distant from East Mediterranean (Turks, Albanians, Greek), Levantine (Syrians, Palestinians, Lebanese), Iranian, Iraqi Kurdish, and Sub-Saharan populations. Conclusions: Emiratis were closely related to Arabian Peninsula populations, West Mediterranean populations and Pakistanis. However, the contribution of East Mediterranean, Levantine Arab, Iranian, and Sub-Saharan populations to the Emiratis’ gene pool appears to be minor.

The development of donor-specific antibodies (DSA) after lung transplantation is common and results in adverse outcomes. In kidney transplantation, Belatacept has been associated with a lower incidence of DSA, but experience with Belatacept in lung transplantation is limited. We conducted a two-center pilot randomized controlled trial of de novo immunosuppression with Belatacept after lung transplantation to assess the feasibility of conducting a pivotal trial. Twenty-seven participants were randomized to Control (Tacrolimus, Mycophenolate Mofetil, and prednisone, n = 14) or Belatacept-based immunosuppression (Tacrolimus, Belatacept, and prednisone until day 89 followed by Belatacept, Mycophenolate Mofetil, and prednisone, n = 13). All participants were treated with rabbit anti-thymocyte globulin for induction immunosuppression. We permanently stopped randomization and treatment with Belatacept after three participants in the Belatacept arm died compared to none in the Control arm. Subsequently, two additional participants in the Belatacept arm died for a total of five deaths compared to none in the Control arm (log rank p = .016). We did not detect a significant difference in DSA development, acute cellular rejection, or infection between the two groups. We conclude that the investigational regimen used in this study is associated with increased mortality after lung transplantation.

This review highlights literature pertinent to chimerism analysis in the context of hematopoietic cell transplantation (HCT). We also conducted a survey of testing practices of program members of CIBMTR worldwide. Questions included testing methods, time points, specimen type, cell lineage tested and testing indications. Recent literature suggests that detection of low level mixed chimerism has a clinical utility in predicting relapse. There is also increasing recognition of HLA loss relapse to potentially guide rescue decisions in cases of relapse. These developments coincide with wider access to high sensitivity next generation sequencing (NGS) in clinical laboratories. Our survey revealed a heterogeneity in practices as well as in findings and conclusions of published studies. Although the most commonly used method is STR, studies support more sensitive methods such as NGS, especially for predicting relapse. There is no conclusive evidence to support testing chimerism in BM over PB, particularly when using a high sensitivity testing method. Periodic monitoring of chimerism especially in diagnoses with a high risk of relapse is advantageous. Lineage specific chimerism is more sensitive than whole blood in predicting impending relapse. Further studies that critically assess how to utilize chimerism testing results will inform evidence based clinical management decisions.