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Bone marrow-derived mesenchymal stem cells (JR-031) for steroid-refractory grade III or IV acute graft-versus-host disease: a phase II/III study

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Abstract

Following a phase I/II study using mesenchymal stem cells (MSCs; JR-031) for steroid-refractory grade II or III acute graft-versus-host disease (aGVHD), a phase II/III study using the cells focused on steroid-refractory grade III or IV aGVHD was conducted. The number of infused MSCs and the number of MSC infusions were the same as the phase I/II study. No additional immunosuppressant was given for steroid-refractory aGVHD during the course of MSC infusions. Twenty-five patients (grade III, 22 patients and grade IV, 3 patients) were enrolled in this study. At 4 weeks after the first MSC infusions, six (24 %) and nine patients (36 %) achieved a complete response (CR) and partial response (PR), respectively. Durable CR by 24 weeks, which was the primary end-point, was obtained in 12 of 25 patients (48 %). At 52 weeks, 12 patients (48 %) treated with MSCs only (six patients) and MSCs plus additional treatments (six patients) were alive in CR. The survival was significantly better in patients showing overall response (OR; CR+PR) than in those showing no OR at 4 weeks. Adverse effects commonly associated with MSC infusions were not observed. Taken together, our two clinical trials suggest JR-031 to be effective for steroid-refractory aGVHD.

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Author information

Authors and Affiliations

  1. Division of Cell Transplantation and Transfusion, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi, 329-0498, Japan

    Kazuo Muroi

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

    Koichi Miyamura

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

    Masaya Okada

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

    Takuya Yamashita

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

    Makoto Murata

  6. Kobe City Medical Center General Hospital, Kobe, Japan

    Takayuki Ishikawa

  7. National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan

    Naokuni Uike

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

    Michihiro Hidaka

  9. Department of Pediatrics, Sappro Hokuyu Hospital, Sapporo, Japan

    Ryoji Kobayashi

  10. Stem Cell Transplantation Center, Hokkaido University Hospital, Sapporo, Japan

    Masahiro Imamura

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

    Junji Tanaka

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

    Kazuteru Ohashi

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

    Shuichi Taniguchi

  14. Division of Hematology and Stem Cell Transplantation, Shizuoka Cancer Center, Nagaizumi-cho, Japan

    Takashi Ikeda

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

    Tetsuya Eto

  16. Division of Hematology, Department of Medicine, Jichi Medical University, Shimotsuke, Japan

    Masaki Mori

  17. Data Science Group, Clinical Intelligence Department, Development Division, JCR Pharmaceuticals Co., Ltd, Ashiya, Japan

    Mariko Yamaoka

  18. Division of Genetic Therapeutics, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Keiya Ozawa

Authors
  1. Kazuo Muroi
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  2. Koichi Miyamura
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  3. Masaya Okada
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  6. Takayuki Ishikawa
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  7. Naokuni Uike
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  8. Michihiro Hidaka
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  10. Masahiro Imamura
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  11. Junji Tanaka
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  12. Kazuteru Ohashi
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  13. Shuichi Taniguchi
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  14. Takashi Ikeda
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  15. Tetsuya Eto
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  16. Masaki Mori
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  18. Keiya Ozawa
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Corresponding author

Correspondence to Kazuo Muroi.

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Conflict of interest

K. Muroi and K. Ozawa received payment for consultancy from JCR Pharmaceuticals Co., Ltd. M. Yamaoka received salary from JCR Pharmaceuticals Co., Ltd. Other authors declare no conflicts of interest.

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Muroi, K., Miyamura, K., Okada, M. et al. Bone marrow-derived mesenchymal stem cells (JR-031) for steroid-refractory grade III or IV acute graft-versus-host disease: a phase II/III study. Int J Hematol 103, 243–250 (2016). https://doi.org/10.1007/s12185-015-1915-9

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  • DOI: https://doi.org/10.1007/s12185-015-1915-9

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