Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Graft-Versus-Host Disease

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

Abstract

The use of mycophenolate mofetil (MMF) for prophylaxis of aGVHD and/or for treatment of acute or chronic GVHD is increasing. However, the benefit of MMF as an alternative to commonly used immunosuppressive agents still needs to be assessed. We ran a retrospective study on 21 consecutive patients (median age, 36 years; range, 20–63) with aGVHD or extensive cGVHD following related (17) or unrelated (4) matched donor SCT (BM, 16; PBSC, 5) who received MMF (2 g/day) because of intolerance to or failure of CsA-containing combinations. Four of the six patients with aGVHD responded, and the response rate was 69% in cGVHD patients. We observed neither significant differences in terms of response rate for skin, liver and bowel nor dissociated response in cases of multiple organ involvement (67% of the patients). Response was the same for lichenoid and sclerodermatous skin cGVHD subtypes. No adverse effects, except diarrhea (three patients), were observed. However, 22 opportunistic or serious viral or bacterial infections occurred in 10 patients. Analysis of trough plasma levels showed a trend for a higher mean MPA concentration in patients responding to MMF. Our study highlights the high risk of infectious complications induced by the administration of MMF, an otherwise efficient and well-tolerated treatment for GVHD.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Kiehl MG, Shipkova M, Basara N et al. New strategies in GVHD prophylaxis Bone Marrow Transplant 2000 25: (Suppl. 2) S16 S19

    Article  PubMed  Google Scholar 

  2. Byrne JL, Stainer C, Hyde H et al. Low incidence of acute graft-versus-host disease and recurrent leukaemia in patients undergoing allogeneic haemopoietic stem cell transplantation from sibling donors with methotrexate and dose-monitored cyclosporin A prophylaxis Bone Marrow Transplant 1998 22: 541 545

    Article  CAS  PubMed  Google Scholar 

  3. Zikos P, Van Lint MT, Frassoni F et al. Low transplant mortality in allogeneic bone marrow transplantation for acute myeloid leukemia: a randomized study of low-dose cyclosporin versus low-dose cyclosporin and low-dose methotrexate Blood 1998 91: 3503 3508

    CAS  PubMed  Google Scholar 

  4. Michallet M, Perrin MC, Belhabri A et al. Impact of cyclosporine and methylprednisolone dose used for prophylaxis and therapy of graft-versus-host disease on survival and relapse after allogeneic bone marrow transplantation Bone Marrow Transplant 1999 23: 145 150

    Article  CAS  PubMed  Google Scholar 

  5. Deeg HJ, Lin D, Leisenring W et al. Cyor cyclosporine plus methylprednisolone for prophylaxis of graft-versus-host disease: a prospective, randomized trial Blood 1997 89: 3880 3887

    CAS  PubMed  Google Scholar 

  6. Hale G, Zhang MJ, Bunjes D et al. Improving the outcome of bone marrow transplantation by using CD52 monoclonal antibodies to prevent graft-versus-host disease and graft rejection Blood 1998 92: 4581 4590

    CAS  PubMed  Google Scholar 

  7. Ratanatharathorn V, Nash RA, Przepiorka 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 2314

    CAS  PubMed  Google Scholar 

  8. Nash RA, Pineiro LA, Storb R et al. FK506 in combination with methotrexate for the prevention of graft-versus-host-disease after marrow transplantation from matched unrelated donors Blood 1996 88: 3634 3641

    CAS  PubMed  Google Scholar 

  9. Deeg HJ . Prophylaxis and treatment of acute graft-versus-host-disease: current state, implications of new immunopharmacologic compounds and future strategies to prevent and treat acute GVHD in high risk patients Bone Marrow Transplant 1994 14: (Suppl. 4) S56 S60

    PubMed  Google Scholar 

  10. Nademanee A, Schmidt GM, Parker P et al. The outcome of matched unrelated donor bone marrow transplantation in patients with hematologic malignancies using molecular typing for donor selection and graft-versus-host-disease prophylaxis regimen of cyclosporine, methotrexate and prednisone Blood 1995 86: 1228 1234

    CAS  PubMed  Google Scholar 

  11. Storb R, Pepe M, Anasetti C et al. What role for prednisone in prevention of acute graft-versus-host disease in patients undergoing marrow transplants? Blood 1990 76: 1037 1045

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  13. Schiller G, Gale RP . Is there an effective therapy for chronic graft-versus-host disease? Bone Marrow Transplant 1993 11: 189 192

    CAS  PubMed  Google Scholar 

  14. 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 

  15. Vogelsang GB . How I treat chronic graft-versus-host disease Blood 2001 97: 1196 1201

    Article  CAS  PubMed  Google Scholar 

  16. Allison AC, Eugui EM . Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF) Clin Transplant 1996 10: 77 84

    CAS  PubMed  Google Scholar 

  17. Sollinger HW . Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients Transplantation 1995 60: 225 243

    Article  CAS  PubMed  Google Scholar 

  18. Halloran P, Mathew T, Tomlanovich S et al. Mycophenolate mofetil in renal allograft recipients: a pooled efficacy analysis of three randomized, double-blind, clinical studies in prevention of rejection Transplantation 1997; 63: 39–47 (erratum, Transplantation 1997 63: 618

    Google Scholar 

  19. Chan TM, Li FK, Tang CSO et al. Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis N Engl J Med 2000 343: 1157 1162

    Article  Google Scholar 

  20. Bornhauser M, Schuler U, Porksen G 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 

  21. Basara N, Blau WI, Kiehl E et al. Mycophenolate mofetil for the prophylaxis of acute GVHD in HLA-mismatched bone marrow transplant patients Clin Transplant 2000 14: 121 126

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  24. Busca A, Saroglia E, 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 

  25. Sullivan KM . Graft-versus-host disease. In: Forman SJ, Blume KG, Thomas ED (eds) Bone Marrow Transplantation Blackwell Scientific: Oxford 1994 339 362

    Google Scholar 

  26. Tsina I, Kaloostian M, Lee R et al. High-performance liquid chromatographic method for the determination of mycophenolate mofetil in human plasma J Chromatogr B 1996 681: 347 353

    Article  CAS  Google Scholar 

  27. Sugioka N, Odani H, Ohta T et al. Determination of a new immunosuppressant, mycophenolate mofetil, and its active metabolite, mycophenolic acid, in rat and human body fluids by high-performance liquid chromatography J Chromatogr B Biomed Appl 1994 654: 249 256

    Article  CAS  PubMed  Google Scholar 

  28. Torgovnick J, Arsura EL, Lala D . Cytomegalovirus ventriculoencephalitis presenting as a Wernicke's encephalopathy-like syndrome Neurology 2000 55: 1910 1913

    Article  CAS  PubMed  Google Scholar 

  29. Weber LT, Shipkova M, Lamersdorf T et al. Pharmacokinetics of mycophenolic acid (MPA) and determinants of MPA free fraction in pediatric and adult renal transplant recipients. German Study Group on Mycophenolate Mofetil Therapy in Pediatric Renal Transplant Recipients J Am Soc Nephrol 1988 9: 1511 1520

    Google Scholar 

  30. Sullivan KM, Witherspoon RP, Storb R et al. Prednisone and azathioprine compared with prednisone and placebo for treatment of chronic graft-versus-host disease: prognostic influence of prolonged thrombocytopenia after allogeneic bone marrow transplantation Blood 1988 72: 546 554

    CAS  PubMed  Google Scholar 

  31. ter Meulen CG, Wetzels JF, Hilbrands LB . The influence of mycophenolate mofetil on the incidence and severity of primary cytomegalovirus infections and disease after renal transplantation Nephrol Dial Transplant 2000 15: 711 714

    Article  CAS  PubMed  Google Scholar 

  32. Sarmiento JM, Dockrell DH, Schwab TR et al. Mycophenolate mofetil increases cytomegalovirus invasive organ disease in renal transplant patients Clin Transplant 2000 14: 136 138

    Article  CAS  PubMed  Google Scholar 

  33. Kiehl MG, Shipkova M, Basara N et al. Mycophenolate mofetil in stem cell transplant patients in relation to plasma level of active metabolite Clin Biochem 2000 33: 203 208

    Article  CAS  PubMed  Google Scholar 

  34. Shaw LM, Holt DW, Keown P et al. Current opinions on therapeutic drug monitoring of immunosuppressive drugs Clin Ther 1999 21: 1632 1652

    Article  CAS  PubMed  Google Scholar 

  35. Mourad M, Malaise J, Chaib Eddour D et al. Correlation of mycophenolic acid pharmacokinetic parameters with side-effects in kidney transplant patients treated with mycophenolate mofetil Clin Chem 2001 47: 88 94

    CAS  PubMed  Google Scholar 

  36. Bullingham R, Nicholls A, Kamm B . Clinical pharmacokinetics of mycophenolate mofetil Clin Pharmacokinet 1998 34: 429 455

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baudard, M., Vincent, A., Moreau, P. et al. 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 30, 287–295 (2002). https://doi.org/10.1038/sj.bmt.1703633

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703633

Keywords

This article is cited by

Search

Quick links