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
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Kiehl MG, Shipkova M, Basara N et al. New strategies in GVHD prophylaxis Bone Marrow Transplant 2000 25: (Suppl. 2) S16 S19
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
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
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
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
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
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
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
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
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
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
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
Schiller G, Gale RP . Is there an effective therapy for chronic graft-versus-host disease? Bone Marrow Transplant 1993 11: 189 192
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
Vogelsang GB . How I treat chronic graft-versus-host disease Blood 2001 97: 1196 1201
Allison AC, Eugui EM . Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF) Clin Transplant 1996 10: 77 84
Sollinger HW . Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients Transplantation 1995 60: 225 243
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
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
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
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
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
Przepiorka D, Weisdorf D, Martin P et al. Consensus Conference on Acute GVHD Grading Bone Marrow Transplant 1995 15: 825 828
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
Sullivan KM . Graft-versus-host disease. In: Forman SJ, Blume KG, Thomas ED (eds) Bone Marrow Transplantation Blackwell Scientific: Oxford 1994 339 362
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
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
Torgovnick J, Arsura EL, Lala D . Cytomegalovirus ventriculoencephalitis presenting as a Wernicke's encephalopathy-like syndrome Neurology 2000 55: 1910 1913
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
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
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
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
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
Shaw LM, Holt DW, Keown P et al. Current opinions on therapeutic drug monitoring of immunosuppressive drugs Clin Ther 1999 21: 1632 1652
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
Bullingham R, Nicholls A, Kamm B . Clinical pharmacokinetics of mycophenolate mofetil Clin Pharmacokinet 1998 34: 429 455
Author information
Authors and Affiliations
Rights 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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1703633
Keywords
This article is cited by
-
Mesenchymal stromal cells plus basiliximab improve the response of steroid-refractory acute graft-versus-host disease as a second-line therapy: a multicentre, randomized, controlled trial
BMC Medicine (2024)
-
Ocular Graft-Versus-Host Disease Topic Review
Current Ophthalmology Reports (2020)
-
Retrospective single center analysis of outcome, risk factors and therapy in steroid refractory graft-versus-host disease after allogeneic hematopoietic cell transplantation
Bone Marrow Transplantation (2019)
-
Inpatient Management of Mucocutaneous GVHD
Current Dermatology Reports (2019)
-
Cutaneous Graft-Versus-Host Disease: Diagnosis and Treatment
American Journal of Clinical Dermatology (2018)