Impact of human leukocyte antigen mismatch on outcomes after unrelated bone marrow transplantation in paediatric patients: A retrospective analysis by the JSTCT HLA working group

Br J Haematol. 2022 Nov;199(3):392-400. doi: 10.1111/bjh.18425. Epub 2022 Aug 27.

Abstract

The impact of human leukocyte antigen (HLA) mismatching at the HLA-A, -B, -C, and -DRB1 loci after unrelated bone marrow transplantation in paediatric patients with haematological malignancies has not been fully examined. Here, we analysed patients with haematological malignancies (all aged ≤15 years; n = 1330) who underwent a first unrelated bone marrow transplantation between 1993 and 2017 in Japan. The results show that although an HLA mismatch was significantly associated with a low relapse rate, it was also associated with higher non-relapse mortality. There was a significant association between HLA mismatch and low overall survival. Locus mismatch analysis revealed that, as in adults, an HLA-C mismatch had a significant negative impact on survival; however, in paediatric patients, an HLA-DRB1 mismatch did not have a negative impact, although these HLA mismatch effects are weakened in recent cases. Taken together, the results suggest that an HLA-matched donor should be the first candidate for paediatric patients; however, for patients without a matched sibling or matched unrelated donor, we can select an unrelated donor with a mismatch at HLA-DRB1 if available.

Keywords: HLA mismatch; haematological malignancy; paediatrics; unrelated bone marrow transplantation.

MeSH terms

  • Bone Marrow Transplantation / methods
  • Child
  • Graft vs Host Disease*
  • HLA Antigens
  • HLA-A Antigens
  • HLA-C Antigens
  • HLA-DRB1 Chains / genetics
  • Hematologic Neoplasms* / therapy
  • Histocompatibility Testing
  • Humans
  • Neoplasm Recurrence, Local
  • Retrospective Studies
  • Unrelated Donors

Substances

  • HLA Antigens
  • HLA-A Antigens
  • HLA-C Antigens
  • HLA-DRB1 Chains