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. 2025 Jul 1;109(7):1241-1250.
doi: 10.1097/TP.0000000000005347. Epub 2025 Feb 14.

Impact of HLA Epitope Matching on Outcomes in Haploidentical HSCT With Distinct GVHD Prophylaxes

Makoto Iwasaki  1 , Junya Kanda  1 , Hidenori Tanaka  2 , Kazuhiro Ikegame  3 , Takero Shindo  4 , Takakazu Kawase  5 , Satoshi Yoshihara  3 , Noriko Doki  6 , Hirohisa Nakamae  7 , Tetsuya Eto  8 , Takashi Tanaka  9 , Takahide Ara  10 , Nobuhiro Hiramoto  11 , Yukio Kondo  12 , Ken-Ichi Matsuoka  13 , Toshihiko Ando  14 , Katsuhiro Shono  15 , Koji Nagafuji  16 , Takahiro Fukuda  9 , Tatsuo Ichinohe  4 , Yoshiko Atsuta  17 , Makoto Murata  18 , Satoko Morishima  19
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Impact of HLA Epitope Matching on Outcomes in Haploidentical HSCT With Distinct GVHD Prophylaxes

Makoto Iwasaki et al. Transplantation. .

Abstract

Background: The introduction of posttransplant cyclophosphamide (PTCy) for prophylaxis against graft-versus-host disease (GVHD) has led to an increase in the number of transplants from haploidentical donors. Accordingly, we aimed to understand the impact of HLA epitope mismatch on the outcomes of haploidentical hematopoietic stem cell transplantation (HSCT) with prophylaxis against GVHD.

Methods: This retrospective study included 1037 patients who underwent their first HSCT for hematologic malignancies from haploidentical peripheral blood donors in a Japanese registry between 2011 and 2019. In total, 542 patients received PTCy and 495 received antithymocyte globulin-based GVHD prophylaxis.

Results: In patients with high-risk disease who received PTCy, higher class I Predicted Indirectly ReCognizable HLA Epitopes (PIRCHE-I) scores were associated with a significantly lower risk of relapse, leading to a higher overall survival (OS: high PIRCHE-I patients compared with low PIRCHE-I patients: relapse: hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.46-0.98; P = 0.040; mortality: HR, 0.69; 95% CI, 0.46-0.99; P = 0.042). In patients with standard-risk disease who received antithymocyte globulin, a significant association between class II PIRCHE (PIRCHE-II) and a lower incidence of nonrelapse mortality (NRM) leading to higher OS was observed (high PIRCHE-II patients compared with low PIRCHE-II patients, NRM: HR, 0.41; 95% CI, 0.19-0.86; P = 0.019; OS: HR, 0.55; 95% CI, 0.32-0.94; P = 0.030).

Conclusions: These findings suggest the differential effects of T-cell epitope matching based on GVHD prophylaxis after haploidentical HSCT. Pretransplant disease status may also be important for understanding the graft-versus-leukemia effect of mismatched HLA in haploidentical HSCT using PTCy.

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Conflict of interest statement

M.I. received grants from JSPS KAKENHI (grant 22K21082). J.K. reports grants from AMED (grant JP18pc0101031), JSPS KAKENHI (grants 18K08325 and 21K08391), and Takeda Science Foundation during the conduct of the study. The other authors declare no conflicts of interest.

References

    1. Ikegame K, Yoshida T, Yoshihara S, et al. Unmanipulated haploidentical reduced-intensity stem cell transplantation using fludarabine, busulfan, low-dose antithymocyte globulin, and steroids for patients in non–complete remission or at high risk of relapse: a prospective multicenter phase I/II study in Japan. Biol Blood Marrow Transplant. 2015;21:1495–1505.
    1. McCurdy SR, Kanakry JA, Showel MM, et al. Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. Blood. 2015;125:3024–3031.
    1. Ciurea SO, Zhang MJ, Bacigalupo AA, et al. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia. Blood. 2015;126:1033–1040.
    1. Martínez C, Gayoso J, Canals C, et al.; Lymphoma Working Party of the European Group for Blood and Marrow Transplantation. Post-transplantation cyclophosphamide-based haploidentical transplantation as alternative to matched sibling or unrelated donor transplantation for Hodgkin Lymphoma: a registry study of the lymphoma working party of the European Society for Blood and Marrow Transplantation. J Clin Oncol. 2017;35:3425–3432.
    1. Takehiko S, Takeo J, Yasuo M, et al. Effect of matching of class I HLA alleles on clinical outcome after transplantation of hematopoietic stem cells from an unrelated donor. N Engl J Med. 1998;339:1177–1185.

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