Abstract
The therapeutic benefits of allogeneic stem cell transplantation in patients with hematologic disorders are limited by the significant morbidity and mortality of graft-versus-host disease (GVHD). Current agents for the prevention and treatment of GVHD have limited efficacy and often result in toxic side-effects. Mycophenolate mofetil (MMF) is a new immunosuppressant with a selective mechanism of action. When employed following solid organ transplantation, MMF reduces the incidence and severity of acute rejection episodes. By selectively targeting activated lymphocytes, the active metabolite of MMF, mycophenolic acid (MPA), appears to augment the actions of standard immunosuppressant agents without adding overlapping toxicities. Studies of combination regimens that include MMF report that this agent permits a dose reduction of cyclosporine, tacrolimus, or corticosteroid, without increasing the incidence of acute rejection in solid organ transplants. Reports on the efficacy of MMF following stem cell transplantation in animal studies were mixed. However, the use of a non-myeloablative conditioning regimen with a post-graft immunosuppressive regimen of MMF and cyclosporine was able to sustain stable mixed chimeras in 60% to 80% of dogs who received hematopoietic grafts from DLA-identical littermates. MMF has demonstrated activity in preliminary clinical trials for GVHD prophylaxis, and treatment of acute or chronic GVHD. Larger clinical trials are warranted to determine the optimum dose and route of MMF administration for GVHD, as well as the comparative safety and efficacy of MMF-containing regimens. Bone Marrow Transplantation (2001) 27, 1255–1262.
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
Anasetti C, Hansen JA . Effect of HLA incompatibility in marrow transplantation from unrelated and HLA-mismatched related donors Transfusion Sci 1994 15: 221–230
Lazarus HM, Vogelsang GB, Rowe JM . Prevention and treatment of acute graft-versus-host disease: the old and the new. A report from The Eastern Cooperative Oncology Group (ECOG) Bone Marrow Transplant 1997 19: 577–600
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
Diasio RB, LoBuglio AF . Immunomodulators: immunosuppressive agents and immunostimulants. In: Hardman JG, Limbird LE, Molinoff PB et al (eds) Goodman & Gilman's The Pharmacological Basis of Therapeutics. 9th edn McGraw-Hill: New York 1996 pp 1291–1307
Eugui EM, Almquist SJ, Muller CD, Allison AC . Lymphocyte-selective cytostatic and immunosuppressive effects of mycophenolic acid in vitro: role of deoxyguanosine nucleotide depletion Scand J Immunol 1991 33: 161–173
Simmons WD, Rayhill SC, Sollinger HW . Preliminary risk-benefit assessment of mycophenolate mofetil in transplant rejection Drug Safety 1997 17: 75–92
Langman LJ, LeGatt DF, Halloran PF, Yatscoff RW . Pharmacodynamic assessment of mycophenolic acid-induced immunosuppression in renal transplant recipients Transplantation 1996 62: 666–672
Grinyó JM . Mycophenolate-update after it has come of age Nephrol Dial Transplant 1999 14: 31–34
Bornhäuser M, Schuler U, Pörksen G et al. Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation Transplantation 1999 67: 499–504
Kiehl MG, Armstrong V, Basara N et al. Intravenous mycophenolate mofetil plus prednisolone and cyclosporine in the prophylaxis of GVHD after stem cell transplantation 41st Annual American Society of Hematology Meeting 1999 Abstr. 671
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
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
Halloran P, Mathew T, Tomlanovich S et al. Mycophenolate mofetil in renal allograft recipients Transplantation 1997 63: 39–47
Pirsch JD, Sollinger HW . Mycophenolate mofetil – clinical and experimental experience Ther Drug Monit 1996 18: 357–361
Kobashigawa J, Miller L, Renlund D et al. A randomized active-controlled trial of mycophenolate mofetil in heart transplant recipients Transplantation 1998 66: 507–515
Jain AB, Hamad I, Rakela J et al. A prospective randomized trial of tacrolimus and prednisone versus tacrolimus, prednisone, and mycophenolate mofetil in primary adult liver transplant recipients. An interim report Transplantation 1998 66: 1395–1398
Sievers TM, Rossi SJ, Ghobrial RM et al. Mycophenolate mofetil Pharmacotherapy 1997 17: 1178–1197
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
Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group . A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation Transplantation 1996 61: 1029–1037
Sollinger HW, US Renal Transplant Mycophenolate Mofetil Study Group . Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients Transplantation 1995 60: 225–232
van Leeuwen L, Guiffre AK, Sewell WA et al. Administration of mycophenolate mofetil in a murine model of acute graft-versus-host disease after bone marrow transplantation Transplantation 1998 64: 1097–1101
Storb R, Yu C, Wagner JL et al. Stable mixed hematopoietic chimerism in DLA-identical littermate dogs given sublethal total body irradiation before and pharmacological immunosuppression after marrow transplantation Blood 1997 89: 3048–3054
Sandmaier BM, Yu C, Gooley T et al. Haploidentical stem cell allografts after nonmyeloablative therapy in a preclinical large animal model 41st Annual American Society of Hematology Meeting 1999 Abstr. 1424
Yu C, Seidel K, Nash RA et al. Synergism between mycophenolate mofetil and cyclosporine in preventing graft-versus-host disease among lethally irradiated dogs given DLA-nonidentical unrelated marrow grafts Blood 1998 91: 2581–2587
Renner U, Platzbecker U, Freiberg-Richter J et al. Intravenous mycophenolate mofetil (MMF) after allogeneic blood stem cell transplantation. Results of a dose-finding study 41st Annual American Society of Hematology Meeting 1999 Abstr. 681
Basara N, Blau WI, Kiehl MG et al. Mycophenolate mofetil for the prophylaxis of acute GVHD in HLA-mismatched bone marrow transplant recipients 40th Annual American Society of Hematology Meeting 1998 Abstr. 4419
McSweeney P, Niederwieser D, Shizuru J et al. Outpatient allografting with minimally myelosuppressive, immunosuppressive conditioning of low-dose TBI and postgrafting cyclosporine (CSP) and mycophenolate mofetil (MMF) 41st Annual American Society of Hematology Meeting 1999 Abstr. 1742
Niederwieser D, Wolff D, Hegenbart U et al. Hematopoietic stem cell transplants (HSCT) from HLA-matched and 1-allele mismatched unrelated donors using a nonmyeloablative regimen 41st Annual American Society of Hematology Meeting 1999 Abstr. 2506
Basara N, Blau WI, Römer 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
Kiehl MG, Armstrong V, Basara N et al. Intravenous mycophenolate mofetil plus prednisolone and cyclosporine in the prophylaxis of GVHD after stem cell transplantation 41st Annual American Society of Hematology Meeting 1999 Abstr. 671
Basara N, Blau IW, Kiehl MG et al. Mycophenolate mofetil in the treatment of acute and chronic GVHD in bone marrow transplant patients: three years' experience 41st Annual American Society of Hematology Meeting 1999 Abstr. 690
Abhyankar S, Godder K, Christiansen N et al. Treatment of resistant acute and chronic graft versus host disease with mycophenolate mofetil 40th Annual American Society of Hematology Meeting 1998 Abstr. 4467
Ilhan O, Celebi H, Arat M et al. Treatment of acute and chronic graft versus host disease with mycophenolate mofetil 41st Annual American Society of Hematology Meeting 1999 Abstr. 4873
Pallotta-Filho RS, Barbosa JAL, Macedo MCMA et al. The use of mycophenolate mofetil in the treatment of refractory chronic graft versus host disease 40th Annual American Society of Hematology Meeting 1998; Abstr. 4489
Redei I, Langston AA, Cherry JK et al. Salvage therapy with mycophenolate mofetil (MMF) for patients with severe chronic GVHD 41st Annual American Society of Hematology Meeting 1999 Abstr. 698
Roberts T, Koc Y, Sprague K et al. Mycophenolate mofetil (MMF) for the treatment of chronic graft versus host disease (cGVHD) of the liver 41st Annual American Society of Hematology Meeting 1999 Abstr. 697
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Vogelsang, G., Arai, S. Mycophenolate mofetil for the prevention and treatment of graft-versus-host disease following stem cell transplantation: preliminary findings. Bone Marrow Transplant 27, 1255–1262 (2001). https://doi.org/10.1038/sj.bmt.1703076
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bmt.1703076
Keywords
This article is cited by
-
Comparison of mycophenolate mofetil and calcineurin inhibitor versus calcineurin inhibitor-based graft-versus-host-disease prophylaxis for matched unrelated donor transplant in acute myeloid leukemia. A study from the ALWP of the EBMT
Bone Marrow Transplantation (2021)
-
Effect of methotrexate dose in graft-versus-host disease prophylaxis after single-unit cord blood transplantation in adult acute myeloid leukemia
International Journal of Hematology (2021)
-
Challenges in managing graft-versus-host disease in developing countries: a perspective
Bone Marrow Transplantation (2019)
-
GvHD prophylaxis after single-unit reduced intensity conditioning cord blood transplantation in adults with acute leukemia
Bone Marrow Transplantation (2017)
-
Pharmacodynamics of T cell function for monitoring pharmacologic immunosuppression after allogeneic hematopoietic stem cell transplantation
International Journal of Hematology (2017)