Mycophenolate mofetil for the prophylaxis of acute GVHD in HLA-mismatched bone marrow transplant patients
N Basara
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorWI Blau
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorMG Kiehl
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorB Schmetzer
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorM Bischoff
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorD Kirsten
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorS Günzelmann
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorAA Fauser
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorN Basara
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorWI Blau
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorMG Kiehl
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorB Schmetzer
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorM Bischoff
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorD Kirsten
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorS Günzelmann
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorAA Fauser
Clinic for Bone Marrow Transplantation and Hematology/Oncology, Idar-Oberstein, Germany
Search for more papers by this authorAbstract
Mycophenolate mofetil (MMF), a new immunosuppressive drug successfully used in renal and heart transplant recipients, was used in combination with cyclosporin A (CsA), methotrexate (MTX) and prednisolone for the prophylaxis of acute graft-versus-host disease (aGVHD) after bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) from human leukocyte antigen (HLA)-mismatched, unrelated (n=9) and related donors (n=4) in an open single-centre phase II study. Thirteen patients, transplanted from HLA-mismatched donors of 18–57 yr of age, received 1 g MMF daily, starting at day 10, in addition to CsA and prednisolone for aGVHD prophylaxis. All patients were engrafted between days 13 and 15. Four of the 13 patients experienced aGVHD grade I/II (n=2) and grade III (n=2). All patients except 3 were alive on day 100 post-transplantation. No severe adverse effects of MMF were recorded. In our pilot study, we demonstrated that MMF can be used safely for the prophylaxis of aGVHD.
References
- 1 Thomas ED, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE, Lerner KG, Buckner CD. Bone marrow transplantation. N Engl J Med 1975: 292: 832.
- 2 Anasetti C, Hansen J. Bone marrow transplantation from HLA-partially matched related donors and unrelated volunteer donors. In: Forman SJ, Blume KG, Thomas ED, eds. Bone Marrow Transplantation. Oxford: Blackwell Scientific Publications, 1994, pp 665–679.
- 3 Hansen JA, Clift RA, Thomas ED, Buckner CD, Storb R, Giblett ER. Transplantation of marrow from an unrelated donor to a patient with acute leukemia. N Engl J Med 1980: 303: 565.
- 4 Beatty PG, Hansen JA, Longton GM, Thomas ED, Sanders JE, Martin P, Bearman SI, Anasetti C, Petersdorf EW, Mickelson EM. Marrow transplantation from HLA-matched, unrelated donors for treatment of hematologic malignancies. Transplantation 1991: 51: 443.
- 5 Ash RC, Casper JT, Chitambar CP, Hansen R, Bunin N, Truitt RL, Murray K, Hunter J, BaxterLowe LA. Successful allogeneic transplantation of T-cell depleted bone marrow from closely HLA-matched unrelated donors. N Engl J Med 1990: 322: 485.
- 6 McGlave P, Bartsch G, Anasetti C, Ash R, Beatty P, Gajewski J, Kernan NA. Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia: initial experience of the National Marrow Donor Program. Blood 1993: 81: 543.
- 7 Kernan NA, Bartsch G, Ash RC, Beatty PG, Champlin R, Filipovich A, Gajewski J, Hansen JA, Henslee Downey J, McCullough J. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. N Engl J Med 1993: 328: 593.
- 8 Nademanee A, Schmidt GM, Parker P, Dagis AC, Stein A, Snyder DS, Odonell M, Smith EP, Stepan DE, Molina A. 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: 6: 1228.
- 9 Storb R, Pepe M, Anasetti C, Appelbaum FR, Beatty P, Doney K, Martin P, Stewart P, Sullivan KM, Witherspoon R. What role for prednisone in prevention of acute graft-versus-host disease in patients undergoing marrow transplants?. Blood 1990: 76: 1037.
- 10 Chao NJ, Schmidt GM, Niland JC, Amylon MD, Dagis AC, Long GD, Nademanee AP, Negrin RS, Odonell MR, Parker PM. Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prophylaxis of acute graft-versus-host disease. N Engl J Med 1993: 329: 1225.
- 11 Allison AC & Eugui EM. Purine metabolism and immunosuppressive effects of mycophenolate mofetil (MMF). Clin Transplantation 1996: 10: 77.
- 12 Sollinger HW. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. Transplantation 1995: 60: 225.
- 13 Kobashigawa J, Miller L, Renlund D, Mentzer R, Alderman E, Bourge R, Costanzo M, Eisen H, Dureau G, Ratkovec R, Hummel M, Ipe D, Johnson J, Keogh A, Mamelok R, Mancini D, Smart F, Valentine H. A randomized active-controlled trial of mycophenolate mofetil in hearth transplant recipients. Transplantation 1998: 66: 507.
- 14 Basara N, Blau IW, Römer E, Rudolphi M, Bischoff M, Kirsten D, Sanchez H, Günzelmann S, Fauser AA. Mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant patients. Bone Marrow Transplant 1998: 22: 61.
- 15 Basara N, Blau IW, Kiehl MG, Roemer E, Rudolphi M, Bischoff M, Kirsten D, Sanchez H, Günzelmann S, Fauser AA. The efficacy and safety of mycophenolate mofetil for the treatment of acute and chronic GVHD in bone marrow transplant recipients. Transplant Proc 1998: 30: 4087.
- 16 Ottinger HD, Albert E, Arnold R, Beelen DW, Blasczyk R, Bunjes D, Burdach S, Ebell W, Ehninger G, Einsele H, Enczmann J, Fauser A, Fridrich W, Finke J, Göbel U, Goldmann SF, Gramatzki M, Helbig W, Kanz L, Klingebiel T, Kolb HJ, Kühni P, Löliger C, Müller CR, GrosseWilde H. German Consensus on immunogenetic donor search for transplantation of allogeneic bone marrow and peripheral blood stem cells. Bone Marrow Transplant 1997: 20: 101.
- 17 Kiehl MG, Armstrong VW, Basara N, Blau IW, Fauser AA. Mycophenolate mofetil for the treatment of severe acute GVHD in stem cell transplant patients in relation to plasma level of active metabolite. Blood 1998: 10(suppl. 1): 1856a.
- 18 Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. Meeting report: Consensus Conference on Acute GVHD grading. Bone Marrow Transplant 1995: 15: 825.
- 19 Socie GG, Landman J, Gluckman E, Devergie A, Raynal B, Esperou Bourdeau H, Brison O. Short-term study of chimerism after bone marrow transplantation for severe aplastic anaemia. Brit J Haematol 1992: 80: 391.
- 20 Van Leeuwen L, Guiffre AK, Sewell WA, Vos BJ, Rainer S, Atkinson K. Administration of mycophenolate mofetil in a murine model of acute graft-versus-host disease after bone marrow transplantation. Transplantation 1997: 64: 1097.
- 21 Bornhäuser M, Schuler U, Pörksen G, Naumann R, Geissler G, Thiede C, Schwerdtfeger R, Ehninger G, Thiede HM. Mycophenolate mofetil and cyclosporine as graft-versus-host disease prophylaxis after allogeneic blood stem cell transplantation. Transplantation 1999: 67: 499.
- 22 Yu C, Seidel K, Nash RA, Deeg HJ, Sandmaier BM, Barsoukov A, Santos E, Storb R. 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.
- 23 Nash RA, Pineiro LA, Storb R, Deeg HJ, Sandmaier BM, Barsoukov A, Santos E, Storb R. FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors. Blood 1996: 88: 3634.
- 24 Ringden O, Remberger M, Runde V, Bornhäuser M, Blau IW, Basara N, Hölig K, Beelen DW, Hägglund H, Basu O, Ehninger G, Fauser AA. Peripheral blood stem cell transplantation from unrelated donors: a comparison with marrow transplantation. Blood 1999: 94: 455.
- 25 Ottinger HD, Beelen DW, Scheulen B, Schaefer UW, Grosse Wilde H. Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow. Blood 1996: 88: 2775.
