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Individual HLAs influence immunological events in allogeneic stem cell transplantation from HLA-identical sibling donors

Bone Marrow Transplantation volume 56, pages 646–654 (2021)Cite this article

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Abstract

In allogeneic hematopoietic stem cell transplantation (allo-HSCT), the effects of patient and donor human leukocyte antigen (HLA) matching status on graft-versus-host disease (GVHD) have been extensively elucidated, but the effects of specific HLAs on acute GVHD remain unclear. Using data from a Japanese registry, we retrospectively analyzed 4392 patients with leukemia or myelodysplastic syndrome who received transplants from HLA-identical sibling donors to investigate the effects of HLAs on acute GVHD. From unbiased searches of HLA-A, -B, and -DR, HLA-B60 was significantly associated with an increased risk of grades II–IV acute GVHD (HR, 1.34; 95% CI, 1.13–1.59; P = 0.001). In contrast, HLA-B62 was significantly associated with a decreased risk of grades II–IV (HR, 0.73; 95% CI, 0.62–0.87; P < 0.001) and III–IV acute GVHD (HR, 0.63; 95% CI, 0.46–0.87; P = 0.005). The risk of leukemia relapse was significantly higher in HLA-B62-positive patients than in HLA-B62-negative patients (HR, 1.23; 95% CI, 1.05–1.43; P = 0.01). Both HLA-B60 and -B62 did not affect overall survival. The findings of this study may by implication suggest the possibility that the effects of specific HLAs on transplant outcomes may reflect inherent biological features, and thus consideration of specific HLAs may be helpful to predict transplant outcomes.

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Fig. 1: Cumulative incidences of grades II–IV acute GVHD.
Fig. 2: Subgroup analysis for effect of HLA-B60 on grades II–IV acute GVHD.
Fig. 3: Subgroup analysis for effect of HLA-B62 on grades II–IV acute GVHD.
Fig. 4: Subgroup analysis for effect of HLA-B62 on leukemia relapse.

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Acknowledgements

The authors thank all of the physicians and data managers who contributed valuable transplantation data to the Japan Society for Hematopoietic Cell Transplantation (JSHCT). We also thank the members of the data management committee of the JSHCT for their assistance. This work was supported by JSPS KAKENHI Grant Number 17K09934, 20K08737, and MEXT KAKENHI Grant Number 19H04811 to SM.

HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation

Satoko Morishima, Yoshiko Atsuta, Kazuhiro Ikegame, Tatsuo Ichinohe, Atae Utsunomiya, Makoto Onizuka, Shunichi Kato, Takakazu Kawase, Junya Kanda, Yoshinobu Kanda, Sung-Won Kim, Takeshi Kobayashi, Yoshifusa Takatsuka, Yoshiyuki Takahashi, Junji Tanaka, Hiroya Tamaki, Masanori Tsuji, Tetsuya Nishida, Yoshinobu Maeda, Masayoshi Masuko, Ryosuke Matsuno, Makoto Murata, Yasuo Morishima, Hisayuki Yokoyama, Atsushi Wake, Nobuhiro Watanabe, Takashi Ashida, Minoko Takanashi, Takumi Hoshino, Toshio Yabe, Kana Sakamoto, Shigeo Fuji, Koichi Miyamura, Nobuyoshi Arima, Eisei Kondo, Koji Kawamura, Takahito Kawata, Kenji Kishimoto, Raine Tatara, Takeshi Hagino, Shin-Ichiro Fujiwara, Yoshimitsu Shimomura, Hirotoshi Sakaguchi, Shigeki Hirabayashi, Hiroto Ishii, Yoshiyuki Onda, Itaru Kato, Akihisa Kawajiri, Takero Shindo, Masahito Tokunaga, Atsushi Nonami, Hiroyuki Muranushi, Noriyoshi Yoshinaga, Naomi Kawashima, Souichi Shiratori, Yuma Tada, Susumu Tanoue, Masahiro Hirayama, Keiko Fukunaga, Marie Ohbiki, Fumihiro Azuma, Minoru Kaneya, Takahiro Fujino, Takaya Yamashita, Shouhei Tomori, Yuki Takeuchi, Takahiko Sato, Kaoru Morita, Norina Tanaka, Fumiya Wada, Taro Edahiro, Makoto Iwasaki, Kento Umino

Author information

Authors and Affiliations

  1. Division of Endocrinology, Diabetes and Metabolism, Hematology and Rheumatology, Second Department of Internal Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan

    Satoko Morishima

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

    Takahiro Fukuda

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

    Noriko Doki

  4. Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan

    Takehiko Mori

  5. Department of Hematology/Oncology, Tokai University School of Medicine, Isehara, Japan

    Makoto Onizuka

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

    Toshihiro Kawakita

  7. Department of Hematology, Meitetsu Hospital, Nagoya, Japan

    Chiaki Kato

  8. Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan

    Yukiyasu Ozawa

  9. Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan

    Masatsugu Tanaka

  10. Department of Cell Therapy and Transplantation Medicine, The University of Tokyo Hospital, Tokyo, Japan

    Mineo Kurokawa

  11. Department of Hematology, Harasanshin Hospital, Fukuoka, Japan

    Tomohiko Kamimura

  12. Department of Hematology/Oncology, Osaka Women’s and Children’s Hospital, Izumi, Japan

    Masami Inoue

  13. Department of Hematology, Tokyo Women’s Medical University, Tokyo, Japan

    Junji Tanaka

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

    Tatsuo Ichinohe

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

    Yoshiko Atsuta

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

    Yoshiko Atsuta

  17. Central Japan Cord Blood Bank, Seto, Japan

    Yasuo Morishima

  18. Department of Hematology and Oncology, Nakagami Hospital, Okinawa, Japan

    Yasuo Morishima

  19. Department of Promotion for Blood and Marrow Transplantation, Aichi Medical University School of Medicine, Nagakute, Japan

    Yasuo Morishima

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  1. Satoko Morishima
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Consortia

on behalf of the HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation

  • Satoko Morishima
  • , Yoshiko Atsuta
  • , Kazuhiro Ikegame
  • , Tatsuo Ichinohe
  • , Atae Utsunomiya
  • , Makoto Onizuka
  • , Shunichi Kato
  • , Takakazu Kawase
  • , Junya Kanda
  • , Yoshinobu Kanda
  • , Sung-Won Kim
  • , Takeshi Kobayashi
  • , Yoshifusa Takatsuka
  • , Yoshiyuki Takahashi
  • , Junji Tanaka
  • , Hiroya Tamaki
  • , Masanori Tsuji
  • , Tetsuya Nishida
  • , Yoshinobu Maeda
  • , Masayoshi Masuko
  • , Ryosuke Matsuno
  • , Makoto Murata
  • , Yasuo Morishima
  • , Hisayuki Yokoyama
  • , Atsushi Wake
  • , Nobuhiro Watanabe
  • , Takashi Ashida
  • , Minoko Takanashi
  • , Takumi Hoshino
  • , Toshio Yabe
  • , Kana Sakamoto
  • , Shigeo Fuji
  • , Koichi Miyamura
  • , Nobuyoshi Arima
  • , Eisei Kondo
  • , Koji Kawamura
  • , Takahito Kawata
  • , Kenji Kishimoto
  • , Raine Tatara
  • , Takeshi Hagino
  • , Shin-Ichiro Fujiwara
  • , Yoshimitsu Shimomura
  • , Hirotoshi Sakaguchi
  • , Shigeki Hirabayashi
  • , Hiroto Ishii
  • , Yoshiyuki Onda
  • , Itaru Kato
  • , Akihisa Kawajiri
  • , Takero Shindo
  • , Masahito Tokunaga
  • , Atsushi Nonami
  • , Hiroyuki Muranushi
  • , Noriyoshi Yoshinaga
  • , Naomi Kawashima
  • , Souichi Shiratori
  • , Yuma Tada
  • , Susumu Tanoue
  • , Masahiro Hirayama
  • , Keiko Fukunaga
  • , Marie Ohbiki
  • , Fumihiro Azuma
  • , Minoru Kaneya
  • , Takahiro Fujino
  • , Takaya Yamashita
  • , Shouhei Tomori
  • , Yuki Takeuchi
  • , Takahiko Sato
  • , Kaoru Morita
  • , Norina Tanaka
  • , Fumiya Wada
  • , Taro Edahiro
  • , Makoto Iwasaki
  •  & Kento Umino

Contributions

SM designed the research, organized the project, performed the statistical analysis, and analyzed the data; YM analyzed and interpreted the data; TF, ND, TM, MO, TKaw, CK, YO, MT, MK, TKam, MI, JT, TI, and YA gathered and organized the data; SM and YM wrote the paper. All authors checked the final version of the paper.

Corresponding author

Correspondence to Satoko Morishima.

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Conflict of interest

MK: Research Funding; Otsuka Pharmaceutical Co., Ltd., Astellas Pharma, Novartis Pharmaceuticals, Pfizer Seiyaku KK, Shionogi & Co., Ltd, Honoraria; Otsuka Pharmaceutical Co., Ltd., Astellas Pharma, Shionogi & Co., Ltd. The other authors declare that they have no conflict of interest.

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Members of the HLA Working Group of the Japan Society for Hematopoietic Cell Transplantation are listed below Acknowledgements.

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Morishima, S., Fukuda, T., Doki, N. et al. Individual HLAs influence immunological events in allogeneic stem cell transplantation from HLA-identical sibling donors. Bone Marrow Transplant 56, 646–654 (2021). https://doi.org/10.1038/s41409-020-01070-3

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