The Association of HLA Antigen and GVHD in Allogeneic Hemopoietic Stem Cell Transplantation with Histocompatible Sibling Donor: A Single-Center Experience in Korea

Abstract

We analyzed the association of HLA antigens with incidence of organ-specific graft-versus-host disease (GVHD) after allogeneic hemopoietic stem cell transplantation (allo-HSCT) from an HLA-matched sibling donor. We retrospectively reviewed the clinical records of allo-HSCT recipients and found 389 patients who had received matched-sibling HSCT. HLA types, GVHD grades, and the development of acute or chronic GVHD, factors that reflect a certain immunological impact associated with involved organs, were investigated. The overall incidence of acute and chronic GVHD was 24.8% (96 cases) and 21.2% (82 cases), respectively. The incidence of acute GVHD with grades II through IV was higher among patients who had HLA-B61 (P = .0153) and HLA-Cw3 (P = .0208). The donor sex (P = .0040) and the conditioning regimen (P = .0010) were also associated with severe acute GVHD. The extensive-type chronic GVHD incidence was higher in patients who had HLA-B54 (P = .0159). The donor sex (P = .0406) and the pretransplantation diagnosis (P = .0184) were other factors associated with the development of extensive-type chronic GVHD. Furthermore, HLA-B35 (P = .0226) and HLA-B54 (P = .0091) were associated with a higher incidence of severe acute skin GVHD and chronic skin and oral GVHD (in descending order of incidence rates). HLA-B7,27 was associated with chronic liver GVHD (P = .0476) in addition to other parameters including patient (P = .0246) and donor sex (P = .0019). This study shows that these remarkable HLA antigens may be potent transplantation immune regulators, but there is a need for further evaluation using larger study samples.

Impact of Human Leukocyte Antigen Loci and Haplotypes on Intestinal Acute Graft-versus-host Disease after Human Leukocyte Antigen-matched Sibling Peripheral Blood Stem Cell Transplantation

“…HLA-A3 and B7 have been reported to have contrasting effects in different studies. [131415161718192021222324] In our study, we found that HLA-A31 allele was a risk factor for intestinal aGVHD. There have been few researches about the influence of HLA haplotypes on aGVHD; we examined this issue and found that HLA-B40-DR15 and HLA-B46-DR9 haplotypes were risk factors for intestinal aGVHD.…”

“…HLA loci have also been reported to have impacts on acute graft-versus-host disease (aGVHD),[131415161718192021222324] which is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the influences of HLA haplotypes on aGVHD have been rarely studied.…”

“…The factors that influence the risk of aGVHD with different grades or target organs may not be all the same even in the same study population. [132526] We chose intestinal aGVHD which is significant in both prevalence and mortality as study object and investigated whether HLA loci and haplotypes played roles in its occurrence. We confined our study in a group of HLA-matched sibling peripheral blood stem cell transplantation (PBSCT) recipients without ex vivo T-cell depletion.…”

Haplotype mismatched transplantation using high doses of peripheral blood CD34+ cells together with stratified conditioning regimens for high-risk adult acute myeloid leukemia patients: a pilot study in a single Korean institution

“…Therefore, the data in this study, showing a relatively lower rate of acute GvHD after haplotype mismatch transplantation, form a basis for population genetics and disease association studies in Korea. 12 Therefore, conditioning regimens in which consideration is given to genetic differences and racial specificity should be evaluated in a larger patient population.…”

The Strategies for the Prevention of Chronic GVHD in Hematopoietic Stem Cell Transplantation

“…[17][18][19] There have been conflicting reports regarding the relationship between hematopoietic growth factor use (G-CSF and GM-CSF) after HCT and the development of GVHD. A meta-analysis of 18 studies including 1,198 patients failed to reveal differences in the incidence of acute or chronic GVHD in patients who did or did not receive hematopoietic growth factors.…”