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Multicenter Study
. 2023 Jun;29(6):347.e1-347.e11.
doi: 10.1016/j.jtct.2023.03.002. Epub 2023 Mar 6.

Epitope Mismatch at HLA-DRB1 Associates with Reduced Relapse Risk in Cord Blood Transplantation for Standard-Risk Hematologic Malignancy

Mari Morita-Fujita  1 , Takero Shindo  2 , Tomoki Iemura  1 , Yasuyuki Arai  3 , Junya Kanda  1 , Kazuya Okada  4 , Yasunori Ueda  4 , Onda Yoshiyuki  5 , Naoyuki Anzai  5 , Takuto Mori  6 , Takayuki Ishikawa  6 , Yasuyuki Otsuka  7 , Akihito Yonezawa  7 , Naoki Yuhi  8 , Kazunori Imada  8 , Akifumi Oba  9 , Mitsuru Itoh  9 , Yoshio Okamoto  10 , Toshiyuki Kitano  10 , Takashi Ikeda  11 , Shinichi Kotani  12 , Takashi Akasaka  12 , Kazuhiro Yago  13 , Mitsumasa Watanabe  14 , Masaharu Nohgawa  15 , Masaaki Tsuji  16 , Tomoharu Takeoka  16 , Ryusuke Yamamoto  17 , Nobuyoshi Arima  18 , Noriyoshi Yoshinaga  19 , Masakatsu Hishizawa  20 , Kouhei Yamashita  1 , Tadakazu Kondo  21 , Akifumi Takaori-Kondo  1 ; Kyoto Stem Cell Transplantation Group
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Free article
Multicenter Study

Epitope Mismatch at HLA-DRB1 Associates with Reduced Relapse Risk in Cord Blood Transplantation for Standard-Risk Hematologic Malignancy

Mari Morita-Fujita et al. Transplant Cell Ther. 2023 Jun.
Free article

Abstract

Cord blood transplantation (CBT) is an attractive therapeutic option for patients with hematologic malignancies. CBT tolerates HLA mismatches between donors and recipients, but the HLA mismatches that generate graft-versus-tumor (GVT) effects remain unknown. Given that HLA molecules contain epitopes comprising polymorphic amino acids that determine their immunogenicity, we investigated associations between epitope-level HLA mismatches and relapse following single-unit CBT. A total of 492 patients with hematologic malignancies who underwent single-unit, T cell-replete CBT were included in this multicenter retrospective study. HLA epitope mismatches (EMs) were quantified using HLA matchmaker software from donor and recipient HLA-A, -B, -C, and -DRB1 allele data. Patients were dichotomized by median EM value and divided into 2 groups: patients who underwent transplantation in complete/partial remission (standard stage: 62.4%) and others (advanced stage: 37.6%). The median number of EMs in the graft-versus-host direction (GVH-EM) was 3 (range, 0 to 16) at HLA class I and 1 (range, 0 to 7) at HLA-DRB1. Higher HLA class I GVH-EM was associated with increased nonrelapse mortality (NRM) in the advanced stage group (adjusted hazard ratio [HR], 2.12; P = .021), with no significant advantage for relapse in either stage. In contrast, higher HLA-DRB1 GVH-EM was associated with better disease-free survival in the standard stage group (adjusted HR, .63; P = .020), which was attributed to lower relapse risk (adjusted HR, .46; P = .014). These associations also were observed even within HLA-DRB1 allele-mismatched transplantations in the standard stage group, indicating that EM might have an impact on relapse risk independent of allele mismatch. High HLA-DRB1 GVH-EM did not increase NRM in either stage. High HLA-DRB1 GVH-EM may lead to potent GVT effects and a favorable prognosis following CBT, especially in patients who underwent transplantation at the standard stage. This approach may facilitate appropriate unit selection and improve the overall prognosis of patients with hematologic malignancies who undergo CBT.

Keywords: Cord blood transplantation; Graft-versus-host disease; Graft-versus-tumor effects; HLA epitope.

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