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Mycophenolate Mofetil Is Effective and Well Tolerated in the Treatment of Refractory Acute and Chronic Graft-versus-Host Disease

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Abstract

We enrolled 11 patients with refractory graft-versus-host disease (GVHD) in a prospective trial evaluating the efficacy of mycophenolate mofetil (MMF). Four (67%) of the 6 patients with acute GVHD and all 5 patients with chronic GVHD responded to MMF. Ten (91%) of the 11 patients were able to decrease steroid use (median decrease, 86%; range, 25%-100%). After a median follow-up of 18 months (range, 1-65 months), 7 patients (64%) remained alive. The adverse events were infectious complications (36%), diarrhea (27%), and neutropenia (18%); the only patient discontinuing MMF did so because of grade 4 neutropenia. This preliminary study suggests that MMF is a well-tolerated agent and has a beneficial effect in the treatment of refractory acute and chronic GVHD.

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References

  1. Martin PJ, Schoch G, Fisher L et al. A retrospective analysis of therapy for acute graft-versus-host disease: secondary treatment. Blood. 1991;77:1821–1828.

    CAS  PubMed  Google Scholar 

  2. Furlong T, Storb R, Anasetti C, et al. Clinical outcome after conversion to FK 506 (tacrolimus) therapy for acute graft-versus-host disease resistant to cyclosporine or for cyclosporine-associated toxicities. Bone Marrow Transplant. 2000;26:985–991.

    Article  CAS  PubMed  Google Scholar 

  3. Carnevale-Schianca F, Martin P, Sullivan K et al.. Changing from cyclosporine to tacrolimus as salvage therapy for chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2000;6:613–620.

    Article  CAS  PubMed  Google Scholar 

  4. Sullivan KM, Witherspoon RP, Storb R, et al. Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease. Blood. 1988;72:555–561.

    CAS  PubMed  Google Scholar 

  5. Wingard JR, Piantadosi S, Vogelsang GB, et al. Predictors of death from chronic graft-versus-host disease after bone marrow transplantation. Blood. 1989;74:1428–1435.

    CAS  PubMed  Google Scholar 

  6. Bolanos-Meade J, Vogelsang GB. Novel strategies for steroid-refractory acute graft-versus-host disease. Curr Opin Hematol. 2005;12:40–44.

    Article  CAS  PubMed  Google Scholar 

  7. Devetten MP, Vose JM. Graft-versus-host disease: how to translate new insights into new therapeutic strategies. Biol Blood Marrow Transplant. 2004;10:815–825.

    Article  PubMed  Google Scholar 

  8. Antin JH, Chen AR, Couriel DR, Ho VT, Nash RA, Weisdorf D. Novel approaches to the therapy of steroid-resistant acute graft-versus-host disease. Biol Blood Marrow Transplant. 2004;10:655–668.

    Article  CAS  PubMed  Google Scholar 

  9. Martin PJ, Carpenter PA, Sanders JE, Flowers ME. Diagnosis and clinical management of chronic graft-versus-host disease. Int J Hematol. 2004;79:221–228.

    Article  PubMed  Google Scholar 

  10. Socie G. Chronic graft-versus-host disease: clinical features and grading systems. Int J Hematol. 2004;79:216–220.

    Article  PubMed  Google Scholar 

  11. Bacigalupo A, Palandri F. Management of acute graft versus host disease (GvHD). Hematol J. 2004;5:189–196.

    Article  CAS  PubMed  Google Scholar 

  12. Mookerjee B, Altomonte V, Vogelsang G. Salvage therapy for refractory chronic graft-versus-host disease with mycophenolate mofetil and tacrolimus. Bone Marrow Transplant. 1999;24:517–520.

    Article  CAS  PubMed  Google Scholar 

  13. Allison AC, Eugui EM. Purine metabolism and immunosuppres-sive effects of mycophenolate mofetil (MMF). Clin Transplant. 1996;10:77–84.

    CAS  PubMed  Google Scholar 

  14. Lipsky JJ. Mycophenolate mofetil. Lancet. 1996;348:1357–1359.

    Article  CAS  PubMed  Google Scholar 

  15. European Mycophenolate Mofetil Cooperative Study Group. Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. Lancet. 1995;345:1321–1325.

    Article  Google Scholar 

  16. Basara N, Blau WI, Kiehl MG, et al. Efficacy and safety of mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant recipient. Transplant Proc. 1998;30:4087–4089.

    Article  CAS  PubMed  Google Scholar 

  17. Basara N, Blau WI, Romer E, et al. Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients. Bone Marrow Transplant. 1998;22:61–65.

    Article  CAS  PubMed  Google Scholar 

  18. Busca A, Saroglia EM, Lanino E, et al. Mycophenolate mofetil (MMF) as therapy for refractory chronic GVHD (cGVHD) in children receiving bone marrow transplantation. Bone Marrow Transplant. 2000;25:1067–1071.

    Article  CAS  PubMed  Google Scholar 

  19. Basara N, Kiehl MG, Blau W, et al. Mycophenolate mofetil in the treatment of acute and chronic GVHD in hematopoietic stem cell transplant patients: four years of experience. Transplant Proc. 2001;33:2121–2123.

    Article  CAS  PubMed  Google Scholar 

  20. Baudard M, Vincent A, Moreau P, Kergueris MF, Harousseau JL, Milpied N. Mycophenolate mofetil for the treatment of acute and chronic GVHD is effective and well tolerated but induces a high risk of infectious complications: a series of 21 BM or PBSC transplant patients. Bone Marrow Transplant. 2002;30:287–295.

    Article  CAS  PubMed  Google Scholar 

  21. Busca A, Locatelli F, Marmont F, Audisio E, Falda M. Response to mycophenolate mofetil therapy in refractory chronic graft-versus-host disease. Haematologica. 2003;88:837–839.

    PubMed  Google Scholar 

  22. Kim JG, Sohn SK, Kim DH, et al. Different efficacy of mycophenolate mofetil as salvage treatment for acute and chronic GVHD after allogeneic stem cell transplant. EurJ Haematol. 2004;73:56–61.

    Article  CAS  Google Scholar 

  23. Lopez F, Parker P, Nademanee A, et al. Efficacy of mycophenolate mofetil in the treatment of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2005;11:307–313.

    Article  CAS  PubMed  Google Scholar 

  24. Shulman HM, Sullivan KM, Weiden PL, et al. Chronic graft-versus-host syndrome in man: a long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980;69:204–217.

    Article  CAS  PubMed  Google Scholar 

  25. Przepiorka D, Weisdorf D, Martin P, et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995;15:825–828.

    CAS  PubMed  Google Scholar 

  26. Hambach L, Stadler M, Dammann E, Ganser A, Hertenstein B. Increased risk of complicated CMV infection with the use of mycophenolate mofetil in allogeneic stem cell transplantation. Bone Marrow Transplant. 2002;29:903–906.

    Article  CAS  PubMed  Google Scholar 

  27. Shapira MY, Hirshfeld E, Weiss L, et al. Mycophenolate mofetil does not suppress the graft-versus-leukemia effect or the activity of lymphokine-activated killer (LAK) cells in a murine model. Cancer Immunol Immunother. 2005;54:383–388.

    Article  CAS  PubMed  Google Scholar 

  28. Weiss L, Reich S, Slavin S. Effect of cyclosporine A and methyl-prednisolone on the graft-versus-leukemia effects across major his-tocompatibility barriers in mice following allogeneic bone marrow transplantation. Bone Marrow Transplant. 1990;6:229–233.

    CAS  PubMed  Google Scholar 

  29. Bacigalupo A, van Lint MT, Occhini D, et al. Increased risk of leukemia relapse with high-dose cyclosporine A after allogeneic marrow transplantation for acute leukemia. Blood. 1991;77:1423–1428.

    CAS  PubMed  Google Scholar 

  30. Hiraoka A, Ohashi Y, Okamoto S, et al. for the Japanese FK506 BMT Study Group. Phase III study comparing tacrolimus (FK506) with cyclosporine for graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation. Bone Marrow Transplant. 2001;28:181–185.

    Article  CAS  PubMed  Google Scholar 

  31. Ruutu T, Hermans J, Niederwieser D, et al. Thrombotic thrombo- cytopenic purpura after allogeneic stem cell transplantation: a survey of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol. 2002;118:1112–1119.

    Article  PubMed  Google Scholar 

  32. Antin JH, Kim HT, Cutler C, et al. Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation. Blood. 2003;102:1601–1605.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medicine, 13-1 Takaramachi, 920-8641, Kanazawa, Ishikawa, Japan

    Akiyoshi Takami, Kanako Mochizuki, Hirokazu Okumura, Hirohito Yamazaki, Masahide Yamazaki, Yukio Kondo, Hidesaku Asakura & Shinji Nakao

  2. Department of Pharmacy, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

    Satsuki Ito & Yukio Suga

Authors
  1. Akiyoshi Takami
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  2. Kanako Mochizuki
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  3. Hirokazu Okumura
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  4. Hirohito Yamazaki
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  5. Masahide Yamazaki
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  6. Yukio Kondo
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  7. Hidesaku Asakura
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  8. Shinji Nakao
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  9. Satsuki Ito
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  10. Yukio Suga
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Correspondence to Akiyoshi Takami.

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Takami, A., Mochizuki, K., Okumura, 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 83, 80–85 (2006). https://doi.org/10.1532/IJH97.05111

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  • DOI: https://doi.org/10.1532/IJH97.05111

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