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Impact of donor type on the outcomes of acute graft versus host disease to systemic corticosteroid therapy

Bone Marrow Transplantation volume 59, pages 1763–1772 (2024)Cite this article

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Abstract

Systemic corticosteroid therapy is a well-established first-line treatment for grades II–IV acute graft-versus-host disease (aGVHD). Recently, several developments have occurred, including the introduction of transplantation from human leukocyte antigen (HLA) haploidentical donors using post-transplant cyclophosphamide (PTCY-Haplo), and improvements in prognosis after cord blood transplantation (CBT) in Japan. This study aimed to analyze the association between donor sources and outcomes in patients with aGVHD. Our study included 2732 patients who developed grades II–IV aGVHD, and were treated with systemic corticosteroids. We compared HLA-matched related donors (MRD), HLA-matched unrelated donors (MUD), PTCY-Haplo, and CBT. We set endpoint as response rate, 1-year cumulative incidence of non-relapse mortality (NRM), and overall survival (OS). The adjusted odds ratios for a complete response (CR) were 0.99 (95% confidence interval [CI]: 0.74–1.31, P = 0.925) for MUD, 2.08 (95% CI: 1.35–3.25, P = 0.001) for PTCY-Haplo, and 1.08 (95% CI: 0.83–1.41, P = 0.550) for CBT compared with MRD. A significant increase in response rates for PTCY were only found in a single-organ involvement. No significant association was observed between the donor source and NRM or OS. In conclusion, PTCY-Haplo is associated with a high response rate in patients with a single-organ aGVHD; however, MUD and CBT were not associated with treatment response.

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Fig. 1: Participant enrollment flowchart.
Fig. 2: Transplant outcomes after the development of acute graft-versus-host disease.
Fig. 3: Non-relapse mortality and overall survival according to treatment response to systemic corticosteroids.

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Data availability

The data for this study are not publicly available because of ethical restrictions that exceed the scope of the recipient’s or donor’s consent for research use in the registry.

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Acknowledgements

The authors thank all the physicians and data managers at the centers that contributed to the collection of data on transplantation for the Japanese Data Center for Hematopoietic Cell Transplantation and TRUMP2.

Author information

Authors and Affiliations

  1. Department of Hematology, Kobe City Hospital Organization Kobe City Medical Center General Hospital, Kobe, Japan

    Yoshimitsu Shimomura & Nobuhiro Hiramoto

  2. Department of Environmental Medicine and Population Science, Graduate School of Medicine, Osaka University, Suita, Japan

    Yoshimitsu Shimomura & Tetsuhisa Kitamura

  3. Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan

    Junichi Sugita

  4. Department of Hematology and Oncology, Okayama University Hospital, Okayama, Japan

    Toshiki Terao

  5. First Department of Internal Medicine, Kansai Medical University, Osaka, Japan

    Atsushi Satake

  6. Department of Hematology, Nippon Medical School, Tokyo, Japan

    Tsuneaki Hirakawa

  7. Department of Hematology, Federation of National Public Service Personnel Mutual Aid Associations toranomon hosplital, Tokyo, Japan

    Naoyuki Uchida

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

    Masashi Shimabukuro

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

    Masatsugu Tanaka

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

    Tetsuya Eto

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

    Keisuke Kataoka

  12. Division of Molecular Oncology, National Cancer Center Research Institute, Tokyo, Japan

    Keisuke Kataoka

  13. Department of hematology, Osaka Metropolitan University, Graduate School of Medicine, Osaka, Japan

    Hirohisa Nakamae

  14. Department of Hematology, NHO Kyusyu Medical Center, Fukuoka, Japan

    Ken Takase

  15. Department of Hematology, NHO Kumamoto Medical Center, Kumamoto, Japan

    Toshiro Kawakita

  16. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Yasuyuki Arai & Junya Kanda

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

    Wataru Takeda & Takahiro Fukuda

  18. Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Kanagawa, Japan

    Fumihiko Ishimaru

  19. Japanese Data Center for Hematopoietic Cell Transplantation, Nagakute, Japan

    Yoshiko Atsuta

  20. Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan

    Yoshiko Atsuta

  21. Division of Hematology, Jichi Medical University Saitama Medical Center, Saitama, Japan

    Hideki Nakasone

  22. Division of Emerging Medicine for Integrated Therapeutics (EMIT), Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan

    Hideki Nakasone

Authors
  1. Yoshimitsu Shimomura
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  2. Tetsuhisa Kitamura
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  3. Junichi Sugita
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  4. Toshiki Terao
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  5. Atsushi Satake
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  6. Tsuneaki Hirakawa
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  7. Naoyuki Uchida
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  8. Masashi Shimabukuro
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  9. Masatsugu Tanaka
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  10. Tetsuya Eto
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  11. Nobuhiro Hiramoto
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  12. Keisuke Kataoka
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  13. Hirohisa Nakamae
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  14. Ken Takase
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  15. Toshiro Kawakita
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  16. Yasuyuki Arai
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  17. Wataru Takeda
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  18. Fumihiko Ishimaru
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  19. Takahiro Fukuda
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  20. Yoshiko Atsuta
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  21. Hideki Nakasone
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  22. Junya Kanda
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Contributions

YS designed the study, developed the models, performed statistical analysis, and wrote the first draft of the manuscript. TK, JS, TT, AS, TH, HN, and JK critically reviewed the data analysis and manuscript. YA managed the unified registry database. HN and JK advised on the methods, revised the manuscript, and were responsible for the co-project of JSTCT Donor/Source and JSTCT GVHD Working Groups, respectively. All the other authors contributed to data collection. All the authors approved the final version of the manuscript.

Corresponding author

Correspondence to Yoshimitsu Shimomura.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate statement

This study was approved by the Data Management Committee of the Japanese Data Center for Hematopoietic Cell Transplantation and the Ethics Committee of the Kobe City Hospital Organization, Kobe City Medical Center General Hospital. All methods were performed in accordance with the relevant guidelines and regulations. Patient consent was obtained prior to registration in the Transplant Registry Unified Management Program 2.

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Shimomura, Y., Kitamura, T., Sugita, J. et al. Impact of donor type on the outcomes of acute graft versus host disease to systemic corticosteroid therapy. Bone Marrow Transplant 59, 1763–1772 (2024). https://doi.org/10.1038/s41409-024-02424-x

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