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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1440911
This article is part of the Research Topic Immunology of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) View all 5 articles

Human leukocyte antigen evolutionary divergence as a novel risk factor for donor selection in acute lymphoblastic leukemia patients undergoing haploidentical hematopoietic stem cell transplantation

Provisionally accepted
Hai-Fei Zhou Hai-Fei Zhou 1*Xing-Yu Cao Xing-Yu Cao 2,3Xiangjun Liu Xiangjun Liu 1Xiaobo Li Xiaobo Li 1
  • 1 Beijing BFR Gene Diagnostics Co., Ltd, Beijing, China
  • 2 Hebei Yanda Hospital, Langfang, Hebei, China
  • 3 Lu Daopei Hospital, Beijing, China

The final, formatted version of the article will be published soon.

    The human leukocyte antigen (HLA) evolutionary divergence (HED) reflects immunopeptidome diversity and has been shown to predict the response of tumors to immunotherapy. Its impact on allogeneic hematopoietic stem cell transplantation (HSCT) is controversial in different studies. In this study, we retrospectively analyzed the clinical impact of class I and II HED in 225 acute lymphoblastic leukemia patients undergoing HSCT from related haploidentical donors. The HED for recipient, donor, and donor-recipient pair was calculated based on Grantham distance, which accounts for variations in the composition, polarity, and volume of each amino acid within the peptide-binding groove of two HLA alleles. The median value of HED scores was used as a cut-off to stratify patients with high or low HED. The class I HED for recipient (R_HED class I ) showed the strongest association with cumulative incidence of relapse (12.2 vs. 25.0%, P = 0.00814) but not with acute graft-versus-host disease.The patients with high class II HED for donor-recipient (D/R_HED class II ) showed a significantly higher cumulative incidence of severe aGVHD than those with low D/R_HED class II (24.0% vs. 6.1%, P = 0.0027). Multivariate analysis indicated that a high D/R_HED class II was an independent risk factor for the development of severe aGVHD (P = 0.007), and a high R_HED class I had a more than two-fold reduced risk of relapse (P = 0.028). However, there was no discernible difference in overall survival (OS) or disease-free survival (DFS) for patients with high or low HED, which was inconsistent with the previous investigation. While the observation are limited by the presented single center retrospective cohort, the results show that HED has poor prognostic value in OS or DFS, as well as the associations with relapse and aGVHD.In haploidentical setting, class II HED for donor-recipient pair (D/R_HED class II ) is an independent and novel risk factor for finding the best haploidentical donor, which could potentially influence clinical practice if verified in larger cohorts.

    Keywords: human leukocyte antigen (HLA) evolutionary divergence (HED), Acute Lymphoblastic Leukemia, Haploidentical hematopoietic stem cell transplantation, Donor Selection, risk factor

    Received: 30 May 2024; Accepted: 01 Aug 2024.

    Copyright: © 2024 Zhou, Cao, Liu and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Hai-Fei Zhou, Beijing BFR Gene Diagnostics Co., Ltd, Beijing, China

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