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Graft-Versus-Host Disease

Low-dose thymoglobulin as second-line treatment for steroid-resistant acute GvHD: an analysis of the JSHCT

Bone Marrow Transplantation volume 52, pages 252–257 (2017)Cite this article

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Abstract

A nationwide retrospective study for the clinical outcomes of 99 patients who had received thymoglobulin at a median total dose of 2.5 mg/kg (range, 0.5–18.5 mg/kg) as a second-line treatment for steroid-resistant acute GvHD was conducted. Of the 92 evaluable patients, improvement (complete or partial response) was observed in 55 patients (60%). Multivariate analysis demonstrated that male sex and grade III and IV acute GvHD were associated with a lower improvement rate, whereas thymoglobulin dose (<2.0, 2.0–3.9 and ⩾4.0 mg/kg) was NS. Factors associated with significantly higher nonrelapse mortality included higher patient age (⩾50 years), grade IV acute GvHD, no improvement of GvHD and higher dose of thymoglobulin (hazard ratio, 2.55; 95% confidence interval, 1.34–4.85; P=0.004 for 2.0–3.9 mg/kg group and 1.79; 0.91–3.55; P=0.093 for ⩾4.0 mg/kg group). Higher dose of thymoglobulin was associated with a higher incidence of bacterial infections, CMV antigenemia and any additional infection. Taken together, low-dose thymoglobulin at a median total dose of 2.5 mg/kg provides a comparable response rate to standard-dose thymoglobulin reported previously, and <2.0 mg/kg thymoglobulin is recommended in terms of the balance between efficacy and adverse effects.

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Acknowledgements

We would like to thank the physicians at each transplantation center and the data manager at the Japanese Data Center for Hematopoietic Cell Transplantation. This study was supported in part by a grant from the Japan Society for the Promotion of Science (JSPS) (15K09498 to MM) and the Japan Agency for Medical Research and Development (AMED) (15ek0510010h0003 to MM).

Author information

Authors and Affiliations

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

    M Murata & T Nishida

  2. Division of Hematology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan

    K Ikegame, H Ogawa & K Kaida

  3. Department of Internal Medicine, Holy Spirit Hospital, Nagoya, Japan

    Y Morishita

  4. Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan

    H Nakamae

  5. Division of Hematology and Stem Cell Transplantation, Shizuoka Cancer Center, Shizuoka, Japan

    T Ikeda

  6. Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan

    M Inoue

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

    T Eto

  8. Department of Hematology, Aomori Prefectural Central Hospital, Aomori, Japan

    K Kubo

  9. Leukemia Research Center, Saiseikai Maebashi Hospital, Maebashi, Japan

    T Sakura

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

    T Mori

  11. Department of Hematology, Toranomon Hospital, Tokyo, Japan

    N Uchida

  12. Division of Hematology and Rheumatology, Department of Internal Medicine, Kinki University, School of Medicine, Osakasayama, Japan

    T Ashida

  13. Department of Hematology, Kawasaki Medical School, Kurashiki, Japan

    Y Matsuhashi

  14. Department of Hematology, Oita Prefectural Hospital, Oita, Japan

    Y Miyazaki

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

    T Ichinohe

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

    Y Atsuta

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

    Y Atsuta

  18. Department of Hematology, Hokkaido University Graduate School of Medical Science, Sapporo, Japan

    T Teshima

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  1. M Murata
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Correspondence to M Murata.

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Appendix

Appendix

Institutes participating in this study: Hokkaido University Hospital; Sapporo Hokuyu Hospital; Sapporo City General Hospital; Aomori Prefectural Central Hospital; Iwate Medical University; University of Tsukuba Hospital; Jichi Medical University Hospital; Gunmaken Saiseikai Maebashi Hospital; Saitama Medical Center; Saitama Medical Center, Jichi Medical University; National Cancer Center Hospital; The Jikei University; Keio University Hospital; Toranomon Hospital; Medical Hospital, Tokyo Medical and Dental University; Kanagawa Cancer Center; Tokai University School of Medicine; Kanagawa Children’s Medical Center; Yokohama Municipal Citizen’s Hospital; Niigata University Medical & Dental Hospital; Toyama Prefectural Central Hospital; Shizuoka Cancer Center; Nagoya University Hospital; Nagoya Medical Center; Aichi Medical University Hospital; Osaka Medical Center for Cancer and Cardiovascular Diseases; Kinki University Hospital, Faculty of Medicine; Osaka University hospital; Osaka City University Hospital; Osaka City General Hospital; Osaka Medical Center and Research Institute for Maternal and Child Health; Matsushita Memorial Hospital; Sakai Hospital Kinki University, Faculty of Medicine; Hirakata Kohsai Hospital; Hyogo College of Medicine; Hyogo Cancer Center; Shimane Prefectural Central Hospital; Okayama University Hospital; Kawasaki Medical School Hospital; Hiroshima University Hospital; Tokushima Red Cross Hospital; Kochi Medical School Hospital; Kyushu University Hospital; Harasanshin Hospital; Hamanomachi Hospital; St Mary’s Hospital; Kurume University Hospital; National Kyushu Medical Center; Kitakyushu Municipal Medical Center; Nagasaki University Hospital; Oita University Hospital; Oita Prefectural Hospital.

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Murata, M., Ikegame, K., Morishita, Y. et al. Low-dose thymoglobulin as second-line treatment for steroid-resistant acute GvHD: an analysis of the JSHCT. Bone Marrow Transplant 52, 252–257 (2017). https://doi.org/10.1038/bmt.2016.247

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