Donor specific HLA antibody in hematopoietic stem cell transplantation: Implications for donor selection

Abstract

Advances in hematopoietic stem cell transplant (HSCT) have led to changes in the approach to donor selection. Many of these new approaches result in greater HLA loci mismatching, either through the selection of haploidentical donors or permissive HLA mismatches. Although these approaches increase the potential of transplant for many patients by expanding the number of acceptable donor HLA genotypes, they add the potential barrier of donor-specific HLA antibodies (DSA). DSA presents a unique challenge in HSCT, as it can limit engraftment and lead to graft failure. However, transient reduction of HLA antibodies through desensitization treatments can limit the risk of graft failure and facilitate engraftment. Thus, the consideration of DSA in donor selection and the management of DSA prior to transplant are playing an increasingly important role in HSCT. In this review, we will discuss studies addressing the role of HLA antibodies in HSCT, the reported impact of desensitization on DSA levels, and the implications for selecting donors for patients with DSA. We found that there is a clear consensus that moderate strength DSA should be avoided, while desensitization strategies are reported to be effective in most cases at reducing DSA to amenable levels. There is limited information regarding the impact of specific characteristics of DSA, such as HLA loci or overall level of sensitization, which could further aid in donor selection for sensitized HSCT candidates.

Applying Rituximab During the Conditioning Regimen Prevents Epstein–Barr Virus Infection Following Allogeneic Hematopoietic Stem Cell Transplant in a Children’s Cohort: A Retrospective Case–Control Study

“…These results are consistent with a recent study that also focused on the administration of rituximab before HSCT [ 30 , 31 ]. Since rituximab has been a recommended treatment for DSA in several studies [ 32 – 35 ], the DSA-positive patients were excluded from the present study.…”

Discovery of three HLA‐DQB1*03:01:01 variants: HLA‐DQB1*03:01:01:54, ‐DQB1*03:01:01:56 and ‐DQB1*03:01:01:58

“…One of the main challenges in allogeneic‐hematopoietic stem cell transplantation is to find the most compatible donor in order to avoid serious adverse events, such as graft‐versus‐host disease 1 . HLA typing using next‐generation sequencing (NGS) offers high‐throughput and high‐resolution capabilities, allowing to improve donor selection 2 .…”

“…Three nucleotide substitutions in intronic regions give rise to the novel alleles: One of the main challenges in allogeneic-hematopoietic stem cell transplantation is to find the most compatible donor in order to avoid serious adverse events, such as graft-versus-host disease. 1 HLA typing using next-generation sequencing (NGS) offers high-throughput and highresolution capabilities, allowing to improve donor selection. 2 Moreover, the use of NGS for routine HLA typing has contributed to the increase in the identification of novel HLA alleles, 3,4 with some 38,008 alleles reported in the IPD-IMGT/HLA Database.…”

Transfusion Support in Hematopoietic Stem Cell Transplantation: A Contemporary Narrative Review

“…41,42 As donor-specific HLA antibodies can lead to poor engraftment and increased incidence of graft failure, patients with extensive HLA sensitization will require coordination between the clinical team, HLA laboratory, blood bank, and blood supplier to ensure safe peri-HSCT PLT transfusion. 3,40,43 To that end, directed blood donations from family members prior to transplantation should be avoided to prevent alloimmunization to minor HLA antigens that could subsequently reduce the pool of the donors most likely to be HLA-compatible (i.e., family members).…”

“…The recent increase in the number and type of diseases for which HSCT may be attempted, coupled with the rise of cord blood utilization, haploidentical transplant, and permissive human leukocyte antigen (HLA) mismatching, has contemporaneously coincided with emerging evidencebased use of restrictive red blood cell (RBC) and platelet (PLT) transfusions. [1][2][3][4][5] Accumulating experience has also led to better characterization of pediatric HSCT, and HSCT in non-malignant conditions such as sickle cell disease. 6,7 While an exhaustive, detailed review of every disease process managed with HSCT is beyond the scope of this ar-ticle, important pearls will be highlighted.…”