Individual HLAs influence immunological events in allogeneic stem cell transplantation from HLA-identical sibling donors

• Published in: Bone marrow transplantation (Basingstoke) Vol. 56; no. 3; pp. 646 - 654
• Main Authors: Morishima, Satoko, Fukuda, Takahiro, Doki, Noriko, Mori, Takehiko, Onizuka, Makoto, Kawakita, Toshihiro, Kato, Chiaki, Ozawa, Yukiyasu, Tanaka, Masatsugu, Kurokawa, Mineo, Kamimura, Tomohiko, Inoue, Masami, Tanaka, Junji, Ichinohe, Tatsuo, Atsuta, Yoshiko, Morishima, Yasuo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2021; Nature Publishing Group
• Subjects: 692/308/2056; 692/308/2171; Antigens; Brothers and sisters; Care and treatment; Cell Biology; Donors; Genetic aspects; Graft versus host reaction; Health aspects; Hematology; Hematopoietic stem cells; Histocompatibility antigen HLA; Histocompatibility antigens; HLA histocompatibility antigens; Homografts; Immunology; Internal Medicine; Leukemia; Leukocytes; Medicine; Medicine & Public Health; Myelodysplastic syndrome; Myelodysplastic syndromes; Patient outcomes; Public Health; Risk; Risk factors; Stem cell transplantation; Stem Cells; Transplantation; Transplants; Transplants & implants; Japan
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/s41409-020-01070-3

In allogeneic hematopoietic stem cell transplantation (allo-HSCT), the effects of patient and donor human leukocyte antigen (HLA) matching status on graft-versus-host disease (GVHD) have been extensively elucidated, but the effects of specific HLAs on acute GVHD remain unclear. Using data from a Japanese registry, we retrospectively analyzed 4392 patients with leukemia or myelodysplastic syndrome who received transplants from HLA-identical sibling donors to investigate the effects of HLAs on acute GVHD. From unbiased searches of HLA-A, -B, and -DR, HLA-B60 was significantly associated with an increased risk of grades II–IV acute GVHD (HR, 1.34; 95% CI, 1.13–1.59; P  = 0.001). In contrast, HLA-B62 was significantly associated with a decreased risk of grades II–IV (HR, 0.73; 95% CI, 0.62–0.87; P  < 0.001) and III–IV acute GVHD (HR, 0.63; 95% CI, 0.46–0.87; P  = 0.005). The risk of leukemia relapse was significantly higher in HLA-B62-positive patients than in HLA-B62-negative patients (HR, 1.23; 95% CI, 1.05–1.43; P  = 0.01). Both HLA-B60 and -B62 did not affect overall survival. The findings of this study may by implication suggest the possibility that the effects of specific HLAs on transplant outcomes may reflect inherent biological features, and thus consideration of specific HLAs may be helpful to predict transplant outcomes.