Skip to main content

Advertisement

SpringerLink
Log in

Use of mycophenolate mofetil in patients received allogeneic hematopoietic stem cell transplantation in Japan

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

We evaluated the use of mycophenolate mofetil (MMF) after hematopoietic stem cell transplantation (HSCT) in Japan from 1999 to 2008. MMF was administered to 301 patients, including 157 for the prevention of graft-versus-host disease (GVHD), 94 for the treatment of acute GVHD and 50 for the treatment of chronic GVHD. The three most common doses were 500 mg twice daily, 250 mg three times daily and 1,000 mg twice daily, given to 63, 54 and 45 patients, respectively. The incidence of grade II–IV acute GVHD was 30.0% and grade III–IV was 20.0% in the GVHD prevention group. Among treated patients, disappearance or improvement of subjective symptoms occurred in 57.0% of acute GVHD patients and in 52.0% of chronic GVHD patients. With regard to safety, the following major adverse events (grade 3 or more) were recorded: 31 infections, 31 neutropenia, 28 thrombocytopenia, 25 diarrhea and 1 renal disorder. A total of 116 patients developed grade 3 or 4 adverse events, but 79 were successfully treated with supportive treatment. Thus, our findings suggest that MMF is safe and effective for the prevention and treatment of GVHD in patients who have received an allogeneic stem cell transplant.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Goker H, Haznedaroglu IC, Chao NJ. Acute graft-vs-host disease: pathobiology and management. Exp Hematol. 2001;29:259–77.

    Article  CAS  PubMed  Google Scholar 

  2. Martin PJ, Schoch G, Fisher L, Byers V, Anasetti C, Appelbaum FR, et al. A retrospective analysis of therapy for acute graft-versus-host disease: initial treatment. Blood. 1990;76:1464–72.

    CAS  PubMed  Google Scholar 

  3. Martin PJ, Carpenter PA, Sanders JE, Flowers ME. Diagnosis and clinical management of chronic graft-versus-host disease. Int J Hematol. 2004;79:221–8.

    Article  PubMed  Google Scholar 

  4. Basara N, Blau WI, Kiehl MG, Romer E, Rudolphi M, Bischoff M, et al. Efficacy and safety of mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant recipient. Transplant Proc. 1998;30:4087–9.

    Article  CAS  PubMed  Google Scholar 

  5. Basara N, Blau WI, Kiehl MG, Schmetzer B, Bischoff M, Kirsten D, et al. Mycophenolate mofetil for the prophylaxis of acute GVHD in HLA-mismatched bone marrow transplant patients. Clin Transplant. 2000;14:121–6.

    Article  CAS  PubMed  Google Scholar 

  6. Basara N, Blau WI, Romer E, Rudolphi M, Bischoff M, Kirsten D, et al. Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients. Bone Marrow Transplant. 1998;22:61–5.

    Article  CAS  PubMed  Google Scholar 

  7. Bolwell B, Sobecks R, Pohlman B, Andresen S, Rybicki L, Kuczkowski E, et al. A prospective randomized trial comparing cyclosporine and short course methotrexate with cyclosporine and mycophenolate mofetil for GVHD prophylaxis in myeloablative allogeneic bone marrow transplantation. Bone Marrow Transplant. 2004;34:621–5.

    Article  CAS  PubMed  Google Scholar 

  8. Bornhauser M, Schuler U, Porksen G, Naumann R, Geissler G, Thiede C, et al. Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation. Transplantation. 1999;67:499–504.

    Article  CAS  PubMed  Google Scholar 

  9. Busca A, Saroglia EM, Lanino E, Manfredini L, Uderzo C, Nicolini B, et al. Mycophenolate mofetil (MMF) as therapy for refractory chronic GVHD (cGVHD) in children receiving bone marrow transplantation. Bone Marrow Transplant. 2000;25:1067–71.

    Article  CAS  PubMed  Google Scholar 

  10. Kim JG, Sohn SK, Kim DH, Lee NY, Suh JS, Lee KS, et al. Different efficacy of mycophenolate mofetil as salvage treatment for acute and chronic GVHD after allogeneic stem cell transplant. Eur J Haematol. 2004;73:56–61.

    Article  CAS  PubMed  Google Scholar 

  11. Mookerjee B, Altomonte V, Vogelsang G. Salvage therapy for refractory chronic graft-versus-host disease with mycophenolate mofetil and tacrolimus. Bone Marrow Transplant. 1999;24:517–20.

    Article  CAS  PubMed  Google Scholar 

  12. Nash RA, Johnston L, Parker P, McCune JS, Storer B, Slattery JT, et al. A phase I/II study of mycophenolate mofetil in combination with cyclosporine for prophylaxis of acute graft-versus-host disease after myeloablative conditioning and allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2005;11:495–505.

    Article  CAS  PubMed  Google Scholar 

  13. Neumann F, Graef T, Tapprich C, Vaupel M, Steidl U, Germing U, et al. Cyclosporine A and mycophenolate mofetil vs cyclosporine A and methotrexate for graft-versus-host disease prophylaxis after stem cell transplantation from HLA-identical siblings. Bone Marrow Transplant. 2005;35:1089–93.

    Article  CAS  PubMed  Google Scholar 

  14. Okamura A, Yamamori M, Shimoyama M, Kawano Y, Kawano H, Kawamori Y, et al. Pharmacokinetics-based optimal dose-exploration of mycophenolate mofetil in allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2008;88:104–10.

    Article  CAS  PubMed  Google Scholar 

  15. Takami A, Mochizuki K, Okumura H, Ito S, Suga Y, Yamazaki H, et al. Mycophenolate mofetil is effective and well tolerated in the treatment of refractory acute and chronic graft-versus-host disease. Int J Hematol. 2006;83:80–5.

    Article  CAS  PubMed  Google Scholar 

  16. Atsuta Y, Suzuki R, Yoshimi A, Gondo H, Tanaka J, Hiraoka A, et al. Unification of hematopoietic stem cell transplantation registries in Japan and establishment of the TRUMP System. Int J Hematol. 2007;86:269–74.

    Article  PubMed  Google Scholar 

  17. Alousi AM, Weisdorf DJ, Logan BR, Bolanos-Meade J, Carter S, Difronzo N, et al. Etanercept, mycophenolate, denileukin, or pentostatin plus corticosteroids for acute graft-versus-host disease: a randomized phase 2 trial from the Blood and Marrow Transplant Clinical Trials Network. Blood. 2009;114:511–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lee SJ, Vogelsang G, Gilman A, Weisdorf DJ, Pavletic S, Antin JH, et al. A survey of diagnosis, management, and grading of chronic GVHD. Biol Blood Marrow Transplant. 2002;8:32–9.

    Article  PubMed  Google Scholar 

  19. Lee SJ, Vogelsang G, Flowers ME. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003;9:215–33.

    Article  CAS  PubMed  Google Scholar 

  20. Furlong T, Martin P, Flowers ME, Carnevale-Schianca F, Yatscoff R, Chauncey T, et al. Therapy with mycophenolate mofetil for refractory acute and chronic GVHD. Bone Marrow Transplant. 2009;44:739–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kanda Y, Chiba S, Hirai H, Sakamaki H, Iseki T, Kodera Y, et al. Allogeneic hematopoietic stem cell transplantation from family members other than HLA-identical siblings over the last decade (1991–2000). Blood. 2003;102:1541–7.

    Article  CAS  PubMed  Google Scholar 

  22. Martin PJ, Storer BE, Rowley SD, Flowers ME, Lee SJ, Carpenter PA, et al. Evaluation of mycophenolate mofetil for initial treatment of chronic graft-versus-host disease. Blood. 2009;113:5074–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Arai S, Vogelsang GB. Management of graft-versus-host disease. Blood Rev. 2000;14:190–204.

    Article  CAS  PubMed  Google Scholar 

  24. Bornhauser M, Thiede C, Schuler U, Platzbecker U, Freiberg-Richter J, Helwig A, et al. Dose-reduced conditioning for allogeneic blood stem cell transplantation: durable engraftment without antithymocyte globulin. Bone Marrow Transplant. 2000;26:119–25.

    Article  CAS  PubMed  Google Scholar 

  25. Krejci M, Doubek M, Buchler T, Brychtova Y, Vorlicek J, Mayer J. Mycophenolate mofetil for the treatment of acute and chronic steroid-refractory graft-versus-host disease. Ann Hematol. 2005;84:681–5.

    Article  CAS  PubMed  Google Scholar 

  26. Nash RA, Antin JH, Karanes C, Fay JW, Avalos BR, Yeager AM, et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood. 2000;96:2062–8.

    CAS  PubMed  Google Scholar 

  27. Ratanatharathorn V, Nash RA, Przepiorka D, Devine SM, Klein JL, Weisdorf D, et al. Phase III study comparing methotrexate and tacrolimus (prograf, FK506) with methotrexate and cyclosporine for graft-versus-host disease prophylaxis after HLA-identical sibling bone marrow transplantation. Blood. 1998;92:2303–14.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by Health and Labour Sciences Research Grants for Clinical Cancer Research from the Ministry of Health, Labour and Welfare, Japan. The authors would like to thank the staff of the Data Center of the Japan Society for Hematopoietic Cell Transplantation and the following collaborating institutions for providing patient data and specimens: Hokkaido University, Sapporo Hokuyu Hospital, Sapporo City General Hospital, Hakodate Municipal Hospital, Aomori Prefectural Central Hospital, Tsukuba University, Gunma University, Saitama Medical University International Medical Center, Chiba University, Jikei University Kashiwa Hospital, National Cancer Center Hospital, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Keio University, Tokyo Women’s Medical University, Kyorinn University, Toranomon Hospital, Tokai University, St. Marianna University Yokohama City Seibu Hospital, Nagaoka Red Cross Hospital, Kouseiren Takaoka Hospital, Kanazawa University, Yamanashi Prefectural Central Hospital, Shinshu University, Nagano Red Cross Hospital, Gifu University, Hamamatsu Medical University, Nagoya University, National Hospital Organization Nagoya Medical Center, Konan Kosei Hospital, Mie University, Yamada Red Cross Hospital, Shiga University, Kyoto University, Kyoto Prefectural University, Kinki University, Osaka City University, Osaka City General Hospital, Matsushita Memorial Hospital, Osaka Medical College, Kitano Hospital, Hyogo College of Medicine, Kobe University, Kurashiki Central Hospital, Hiroshima University, National Hospital Organization Kure Medical Center, Yamaguchi University, Tokushima University, Tokushima Red Cross Hospital, Kagawa University, Ehime Prefectural Central Hospital, Ehime University, Kyushu University First Department of Internal Medicine, Kyusyu University Third Department of Internal Medicine, Hamanomachi Hospital, National Organization Kyusyu Cancer Center, Nagasaki University, Sasebo City General Hospital, Oita University, Kyusyu University Hospital at Beppu, Imamura Bun-in Hospital and Kagoshima University.

Author information

Authors and Affiliations

  1. Department of HSCT Data Management and Biostatistics, Nagoya University School of Medicine, Nagoya, Japan

    Minako Iida, Yoshiko Atsuta & Ritsuro Suzuki

  2. Department of Promotion for Blood and Marrow Transplantation, Aichi Medical University School of Medicine, 21, Karimata, Yazako, Nagakute-cho, Aichi-gun, Aichi, 480-1195, Japan

    Minako Iida & Yoshihisa Kodera

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

    Takahiro Fukuda

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

    Kazuhiro Ikegame, Satoshi Yoshihara & Hiroyasu Ogawa

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

    Shuichi Taniguchi

  6. Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

    Akiyoshi Takami

  7. Department of Medicine and Bioregulatory Science, Graduate School of Medical Science, Kyusyu University, Fukuoka, Japan

    Yasunobu Abe

  8. Department of Hematology, Osaka City University Graduate School of Medicine, Osaka, Japan

    Masayuki Hino

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

    Tetsuya Etou

  10. Department of Hematology, Kurashiki Central Hospital, Okayama, Japan

    Yasunori Ueda

  11. Third Department of Internal Medicine, Yamaguchi University School of Medicine, Yamaguchi, Japan

    Toshiaki Yujiri

  12. Department of Hematology, Kobe University Graduate School of Medicine, Hyogo, Japan

    Toshimitsu Matsui & Atsuo Okamura

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

    Junji Tanaka

Authors
  1. Minako Iida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takahiro Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kazuhiro Ikegame
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Satoshi Yoshihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroyasu Ogawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shuichi Taniguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Akiyoshi Takami
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yasunobu Abe
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Masayuki Hino
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Tetsuya Etou
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yasunori Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Toshiaki Yujiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Toshimitsu Matsui
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Atsuo Okamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Junji Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Yoshiko Atsuta
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Yoshihisa Kodera
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Ritsuro Suzuki
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Minako Iida.

About this article

Cite this article

Iida, M., Fukuda, T., Ikegame, K. et al. Use of mycophenolate mofetil in patients received allogeneic hematopoietic stem cell transplantation in Japan. Int J Hematol 93, 523–531 (2011). https://doi.org/10.1007/s12185-011-0817-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-011-0817-8

Keywords

Search

Navigation