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Low-dose antithymocyte globulin inhibits chronic graft-versus-host disease in peripheral blood stem cell transplantation from unrelated donors

Bone Marrow Transplantation volume 56, pages 2231–2240 (2021)Cite this article

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Abstract

Antithymocyte globulin (ATG) has been shown to reduce chronic graft-versus-host disease (GVHD) particularly in allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors; however, anti-GVHD effects of lower doses of ATG remains to be elucidated. We conducted a nationwide retrospective study to compare the outcomes of unrelated PBSCT with or without rabbit ATG (thymoglobulin) in 287 patients. A median ATG dose was 2.0 mg/kg. The primary endpoint, the cumulative incidence of moderate–severe chronic GVHD at 2 years was 22.1% in the ATG group, which was significantly less than that in the non-ATG group (36.3%, P = 0.025). The ATG group had a higher incidence of immunosuppressant discontinuation, GVHD-free, relapse-free survival, and moderate–severe chronic GVHD-free, relapse-free survival at 2 years compared to the non-ATG group. The incidences of grade III–IV aGVHD and moderate–severe chronic GVHD were significantly higher in patients with high absolute lymphocyte count (ALC) before the administration of ATG, whereas relapse rate was significantly higher in patients with low ALC before ATG. In conclusion, low-dose ATG effectively suppresses chronic GVHD in unrelated PBSCT, and ALC before ATG may be a potential predictor for GVHD and relapse.

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Fig. 1: Impacts of ATG on the incidence of cGVHD and off-immunosuppressants, and the probability of GRFS and M/S CRFS.
Fig. 2: Association of ALC before ATG with aGVHD, cGVHD, and relapse.

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Acknowledgements

We thank all the physicians and data managers who contributed valuable data to Transplant Registry Unified Management Program, especially those who participated in the additional survey. They also thank the staff of the Japanese Data Center for Hematopoietic Cell Transplantation for their assistance. This study was collaborated by HLA-WG and GVHD-WG in JSHCT. This study was supported by the Japan Agency for Medical Research and Development (AMED, 20ek0510025h0003).

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Authors and Affiliations

  1. Department of Hematology, Hokkaido University Hospital, Sapporo, Japan

    Souichi Shiratori, Junichi Sugita, Daigo Hashimoto & Takanori Teshima

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

    Shigeo Fuji

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

    Jun Aoki & Takahiro Fukuda

  4. Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan

    Masashi Sawa

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

    Yukiyasu Ozawa

  6. Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan

    Daigo Hashimoto & Takanori Teshima

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

    Ken-ichi Matsuoka

  8. Department of Hematology, Japanese Red Cross Osaka Hospital, Osaka, Japan

    Kazunori Imada

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

    Noriko Doki

  10. Department of Hematology and Rheumatology, Faculty of Medicine, Kindai University Hospital, Osakasayama, Japan

    Takashi Ashida

  11. Department of Hematology/Oncology and Transfusion and Hemapheresis Center, Kurashiki Central Hospital, Kurashiki, Japan

    Yasunori Ueda

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

    Masatsugu Tanaka

  13. Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan

    Yasushi Sawayama

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

    Tatsuo Ichinohe

  15. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Seitaro Terakura

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

    Satoko Morishima

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

    Yoshiko Atsuta

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  1. Souichi Shiratori
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SF reports grants and personal fees from CSL Behring, outside the submitted work. MS reports personal fees from Chugai, Pfizer, Astellas, Nippon-Shinyaku, Ono, MSD, Bristol-Myers Squibb, Kyowa-Hakko Kirin, Asahi-Kasei, Novartis, Eisai, Otsuka, Sumitomo Dainippon, Sanofi, Takeda, Celgene, Mochida, Shire, Mundipharma, outside the submitted work. KM reports personal fees from Kyowa Kirin Co. Ltd., Astellas Pharma Inc., Chugai Pharmaceutical Co. Ltd., Novartis Pharma Inc., Bristol-Myers Squibb, Ono Pharmaceutical Co. Ltd., MSD K.K., JIMRO Co. Ltd., outside the submitted work. KI reports personal fees from Chugai Pharmaceutical Co. Ltd., Kyowa Hakko Kirin Co. Ltd., Novartis Pharma K.K., Celgene Co. Ltd., Bristol-Myers Squibb K.K., Takeda Pharmaceutical Co. Ltd., Nippon Shinyaku Co. Ltd., Otuka Pharmaceutical Co. Ltd., Astellas Pharma Inc., outside the submitted work. TI reports other from Astellas Pharma, Chugai Pharmaceutical Co., CSL Behring, Eisai Co., FUJIFILM Wako Chemicals., Kyowa Kirin Co., Ono Pharmaceutical Co., Pfizer, Nippon Shinyaku Co., MSD, Otsuka Pharmaceutical Co., Repertoire Genesis Inc., Sumitomo Dainippon Pharma Co., Taiho Pharmaceutical Co., other from Takara Bio Inc., Takeda Pharmaceutical Co., Zenyaku Kogyo Co., personal fees from Bristol-Myers Squibb, Celgene, personal fees from Janssen Pharmaceutical K.K., Kyowa Kirin Co., outside the submitted work. ST reports personal fees from Chugai Pharmaceutical Co. Ltd., Yakult Honsha Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Sumitomo Dainippon Pharma, Astellas Pharma Inc., Novartis, Amgen Astellas BioPharma K. K., outside the submitted work. YA reports grants from AMED, during the conduct of the study; other from Astellas Pharma Inc., Mochida Pharmaceutical Co. Ltd., Meiji Seika Pharma Co. Ltd., Chugai Pharmaceutical Co. Ltd., Kyowa Kirin Co. Ltd, outside the submitted work. TT reports personal fees from Merck Sharp & Dohme, grants and personal fees from Kyowa Kirin, personal fees from Takeda, grants, personal fees, and non-financial support from Novartis, personal fees from Pfizer, Bristol-Myers Squibb, grants from Chugai, Sanofi, Astellas, Teijin Pharma, Fuji Pharma, Nippon Shinyaku, non-financial support from Janssen, grants from Japan Society for the Promotion of Science KAKENHI (17H04206), The Center of Innovation Program from Japan Science and Technology Agency, during the conduct of the study.

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Shiratori, S., Sugita, J., Fuji, S. et al. Low-dose antithymocyte globulin inhibits chronic graft-versus-host disease in peripheral blood stem cell transplantation from unrelated donors. Bone Marrow Transplant 56, 2231–2240 (2021). https://doi.org/10.1038/s41409-021-01314-w

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