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Mycophenolate mofetil combined with tacrolimus and minidose methotrexate after unrelated donor bone marrow transplantation with reduced-intensity conditioning

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Abstract

We evaluated the efficacy of a post-grafting immunosuppressive regimen consisting of tacrolimus, methotrexate, and mycophenolate mofetil (MMF) in 21 adults (median age, 55 years) with poor-risk hematologic malignancy who underwent unrelated bone marrow transplantation after fludarabine-based reduced-intensity conditioning (RIC). In combination with intravenous tacrolimus and minidose methotrexate (5 mg/m2 on days 1, 3, and 6), MMF was orally administered at 30 mg/kg daily in three divided doses between days 7 and 27. All patients achieved neutrophil recovery with donor-type chimerism at a median of 19 days (range, 13–35). Cumulative incidences of grades II–IV and III–IV acute graft-versus-host disease (GVHD) were 33% (95% CI, 15–53%) and 5% (95% CI, 0.3–20%), respectively. Five of 20 evaluable patients developed extensive chronic GVHD. Toxicities associated with the use of MMF were acceptable, although one patient experienced intractable GVHD immediately after the cessation of MMF. With a median follow-up of 24 months, overall survival at 3 years was 38% (95% CI, 14–63%). No late graft failure was observed. In conclusion, post-transplant MMF combined with tacrolimus and methotrexate was well tolerated and conferred stable donor cell engraftment, low risk of severe acute GVHD, and encouraging overall survival in unrelated donor marrow transplantation after RIC regimens.

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Acknowledgments

The authors thank Dr. Martin Körbling (Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center) for his assistance in developing our transplant program and critical reading of the manuscript. We also thank the physicians and nurses at Kyoto University Hospital for their dedicated care for the patients and donors.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto, 606-8507, Japan

    Chisaki Mizumoto, Junya Kanda, Tatsuo Ichinohe, Takayuki Ishikawa, Masashi Matsui, Norimitsu Kadowaki, Tadakazu Kondo, Masakatsu Hishizawa, Hiroshi Kawabata, Momoko Nishikori, Kouhei Yamashita, Akifumi Takaori-Kondo, Toshiyuki Hori & Takashi Uchiyama

  2. Department of Hematology, Kokura Memorial Hospital, Kita-kyushu, Japan

    Kazunori Imada

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  1. Chisaki Mizumoto
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Correspondence to Tatsuo Ichinohe.

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Mizumoto, C., Kanda, J., Ichinohe, T. et al. Mycophenolate mofetil combined with tacrolimus and minidose methotrexate after unrelated donor bone marrow transplantation with reduced-intensity conditioning. Int J Hematol 89, 538–545 (2009). https://doi.org/10.1007/s12185-009-0306-5

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