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Use of mycophenolate mofetil and a calcineurin inhibitor in allogeneic hematopoietic stem-cell transplantation from HLA-matched siblings or unrelated volunteer donors: Japanese multicenter phase II trials

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Abstract

To test the feasibility of mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis in Japanese patients, we conducted two multicenter prospective phase II trials of allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA-matched related donors (MRD group) with MMF and cyclosporine or HLA 7–8/8 allele-matched unrelated bone-marrow donors (URD group) with MMF and tacrolimus. The cumulative incidences of grade II–IV acute GVHD on day 100, which was the primary endpoint in these trials, were 45.0% (90% CI 25.8–62.5) and 25.8% (90% CI 13.9–39.5) in the MRD (n = 20) and URD (n = 31) groups, respectively. The rates of 3-year overall survival and non-relapse mortality were 80.0 and 15.0% in the MRD group and 74.2 and 6.5% in the URD group, respectively. GVHD prophylaxis with MMF may lead to a lower incidence of severe mucositis and faster neutrophil engraftment compared to that with methotrexate. A pharmacokinetics study of mycophenolic acid (MPA) showed that a relatively higher plasma concentration of MPA was associated with a lower incidence of acute GVHD. In conclusion, the results of these studies suggest that GVHD prophylaxis with MMF may be useful as an alternative in Japanese patients who may benefit from faster engraftment or less severe mucositis after allogeneic HSCT.

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Acknowledgements

We thank all the participating patients, the medical staff who provided care for these patients, and the data managers of the Japan Clinical Research Support Unit.

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Authors and Affiliations

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

    Takahiko Nakane, Hirohisa Nakamae & Masayuki Hino

  2. Division of Biostatistics, Tohoku University Graduate School of Medicine, Miyagi, Japan

    Takuhiro Yamaguchi

  3. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Saiko Kurosawa, Shigeo Fuji & Takahiro Fukuda

  4. Department of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan

    Atsuo Okamura & Kimikazu Yakushijin

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

    Michihiro Hidaka

  6. Department of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan

    Akio Kohno

  7. Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    Takeshi Saito

  8. Department of Hematology, Seichokai Fuchu Hospital, Izumi, Japan

    Yasutaka Aoyama

  9. Department of Hematology/Oncology, Wakayama Medical University Hospital, Wakayama, Japan

    Kazuo Hatanaka

  10. Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

    Yoshio Katayama & Toshimitsu Matsui

  11. Department of Clinical Pharmacy, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women’s University, Hyogo, Japan

    Motohiro Yamamori

  12. Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan

    Akiyoshi Takami

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  1. Takahiko Nakane
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  2. Hirohisa Nakamae
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  18. Takahiro Fukuda
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Correspondence to Takahiro Fukuda.

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Conflict of interest

This work was supported in part by grants from the National Cancer Research and Development Fund (26-A-26) and Health and Labour Sciences Research Grants (Gan Rinsho) from the Ministry of Health, Labour and Welfare, Japan. HN and MH received grants and personal fees from CHUGAI PHARMACEUTICAL CO.,LTD., outside the submitted work. AT received grant from CHUGAI PHARMACEUTICAL CO.,LTD., outside the submitted work. All other authors have no conflicts of interest to disclose.

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Nakane, T., Nakamae, H., Yamaguchi, T. et al. Use of mycophenolate mofetil and a calcineurin inhibitor in allogeneic hematopoietic stem-cell transplantation from HLA-matched siblings or unrelated volunteer donors: Japanese multicenter phase II trials. Int J Hematol 105, 485–496 (2017). https://doi.org/10.1007/s12185-016-2154-4

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