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Impact of HLA disparity on the risk of overall mortality in patients with grade II–IV acute GVHD on behalf of the HLA Working Group of Japan Society for Hematopoietic Cell Transplantation

Bone Marrow Transplantation volume 56, pages 2990–2996 (2021)Cite this article

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Abstract

Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Stem cell source or HLA disparity may exert a significant impact on the overall survival (OS) after the development of aGVHD. In order to clarify this point, we performed a retrospective analysis using a database of the Japan Society for HCT. We analyzed the clinical outcomes of 10,035 patients who developed grade II–IV aGVHD. The median age of the patients was 48 years. The probability of 2-year OS after the onset of grade II–IV aGVHD in the study cohort was 54.1%. The multivariate analysis showed that the HLA ≥2-loci mismatched related donor and HLA 1-locus mismatched unrelated donor were significantly associated with an inferior OS after grade II–IV aGVHD. In a subgroup analysis, peripheral blood stem cells and HLA disparity were associated with an inferior OS in patients who received related or unrelated HCT. Thus, the clinical outcome after grade II–IV aGVHD significantly varied as per the combination of the presence of HLA disparity and stem cell source. Further research using other databases is necessary to confirm our findings.

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Fig. 1: Overall survival in the whole cohort.
Fig. 2: Overall survival in patients who received a related HSCT.
Fig. 3: Overall survival in patients who received an unrelated HSCT.
Fig. 4: Overall survival in patients who received a cord blood transplant.

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Acknowledgements

This study was partly supported by Health, Labor and Welfare Sciences Research Grants (20FF1002).

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Authors and Affiliations

  1. Department of Hematology, Osaka International Cancer Institute, Osaka, Japan

    Shigeo Fuji

  2. Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka, Japan

    Akitoshi Hakoda & Ayumi Shintani

  3. Department of Hematology, Kyoto University Hospital, Kyoto, Japan

    Junya Kanda & Tadakazu Kondo

  4. Department of Hematology, Nagoya University Hospital, Nagoya, Aichi, Japan

    Makoto Murata & Seitaro Terakura

  5. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan

    Yoshihiro Inamoto

  6. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations Toranomon Hospital, Tokyo, Japan

    Naoyuki Uchida & Takahiro Fukuda

  7. Hematology Division, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Takashi Toya

  8. Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan

    Tetsuya Eto

  9. Department of Hematology, Osaka City University Hospital, Osaka, Japan

    Hirohisa Nakamae

  10. Department of Hematology, Hyogo College of Medicine Hospital, Hyogo, Japan

    Kazuhiro Ikegame

  11. Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan

    Masatsugu Tanaka

  12. Department of Hematology, National Hospital Organization Kumamoto Medical Center, Kumamoto, Japan

    Toshiro Kawakita

  13. Hematology, Oncology & Cardiovascular medicine, Kyushu University Hospital, Fukuoka, Japan

    Toshihiro Miyamoto

  14. Department of Hematology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    Tatsuo Ichinohe

  15. Preparation Department, Japanese Red Cross Kinki Block Blood Center, Osaka, Japan

    Takafumi Kimura

  16. Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan

    Yoshiko Atsuta

  17. Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan

    Yoshiko Atsuta

  18. Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan

    Satoko Morishima

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  1. Shigeo Fuji
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  2. Akitoshi Hakoda
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  19. Yoshiko Atsuta
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  20. Ayumi Shintani
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Contributions

MY, AU, SF, HF, TF, and KK designed the research, organized the project, and wrote the paper. MY performed the statistical analyses. H Ogawa, YT, KI, AY, H Okumura, KI, AN, TE, AY, KM, J Tsukada, J Tanaka, and YA gathered the data. All authors contributed to the final version of the manuscript and have approved it for submission for publication.

Corresponding author

Correspondence to Shigeo Fuji.

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Competing interests

HN received honoraria from Amgen Astellas BioPharma K.K., Astellas Pharma Inc., Otsuka Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Kyowa-Hakko Kirin Co., Ltd., Shire Japan KK., Celgene Corporation, Daiichi Sankyo Company., Ltd., Takeda Pharmaceutical Company Limited., Chugai Pharmaceutical Co., Ltd., Japan Blood Products Organization, Nippon Shinyaku Co., Ltd., Novartis, Pfizer Japan Inc, Bristol-Myers Squibb Company, and research funding from Astellas Pharma Inc, Otsuka Pharmaceutical Co. Ltd., Novartis and Bristol-Myers Squibb Company.

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Fuji, S., Hakoda, A., Kanda, J. et al. Impact of HLA disparity on the risk of overall mortality in patients with grade II–IV acute GVHD on behalf of the HLA Working Group of Japan Society for Hematopoietic Cell Transplantation. Bone Marrow Transplant 56, 2990–2996 (2021). https://doi.org/10.1038/s41409-021-01443-2

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