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Graft Versus Host Disease

Mycophenolate mofetil (MMF) as therapy for refractory chronic GVHD (cGVHD) in children receiving bone marrow transplantation

Bone Marrow Transplantation volume 25, pages 1067–1071 (2000)Cite this article

Abstract

Mycophenolate mofetil (MMF) is an alternative immunosuppressant which inhibits the proliferation of T and B lymphocytes. The purpose of the present study was to evaluate the safety and efficacy of MMF as salvage therapy for chronic GVHD (cGVHD) in children receiving allogeneic bone marrow transplantation. Fifteen children, 3–16 years of age, who had received grafts from HLA-compatible siblings (n = 8), partially matched related donors (n = 2) or matched unrelated donors (n = 5), developed extensive cGVHD which had proved unresponsive to standard immunosuppressive therapy. Patients were treated with MMF at the dose of 15–40 mg/kg/day in combination with other immunosuppressive therapy for a median of 4 months (range 1–15 months). The overall response rate (complete or partial response) was 60%. Thirteen percent had only minor responses, whereas 27% of patients had progressive disease. Best responses were seen in patients with GI tract (60% of complete responses) or mouth (33% of complete responses) cGVHD and skin involvement (43% of complete responses) that did not include sclerodermatous manifestations. Once MMF was started, improvements in the clinical manifestations of cGVHD allowed a significant reduction of steroids in 45% of patients and discontinuation in 27% of cases. Six patients (40%) experienced adverse events, with gastrointestinal symptoms predominating. Five patients experienced opportunistic infections. MMF was discontinued after 35–180 days in six patients for the following reasons: parents choice (n = 2), liver toxicity (n = 1), poor compliance (n = 2), and no response (n = 1). In conclusion, these preliminary results suggest that MMF in combination with other immunosuppressive agents may have a role to play in patients with cGVHD. Prospective clinical trials are needed to establish exact indications for therapy and dosage scheduling. Bone Marrow Transplantation (2000) 25, 1067–1071.

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References

  1. Ferrara JLM, Deeg HJ . Graft-versus-host disease New Engl J Med 1991 324: 667–674

    Article  CAS  Google Scholar 

  2. Locatelli F, Uderzo C, Dini G et al. Graft-versus-host disease in children: the AIEOP-BMT Group experience with cyclosporine A Bone Marrow Transplant 1993 12: 627–633

    CAS  PubMed  Google Scholar 

  3. Sullivan KM, Witherspoon RP, Storb R et al. Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-versus-host disease Blood 1998 72: 555–561

    Google Scholar 

  4. 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 

  5. 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  Google Scholar 

  6. Nash RA, Furlong T, Storb R et al. Mycophenolate mofetil (MMF) as salvage treatment for graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT): safety analysis Blood 1997 90: (Suppl. 1) 105a

    Google Scholar 

  7. 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  Google Scholar 

  8. Sullivan KM . Graft-versus-host disease. In: Forman SJ, Blume KG, Thomas ED (eds) Bone Marrow Transplantation Blackwell Scientific: Boston 1994 p353

    Google Scholar 

  9. Hebert MF, Ascher NL, Lake JR et al. Four-year follow-up of mycophenolate mofetil for graft rescue in liver allograft recipients Transplantation 1999 67: 707–712

    Article  CAS  Google Scholar 

  10. Sollinger HW . Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients: US Renal Transplant Mycophenolate Mofetil Study Group Transplantation 1995 60: 225–232

    Article  CAS  Google Scholar 

  11. Sweeney MJ, Hoffman DH, Esterman MA . Metabolism and biochemistry of mycophenolic acid Cancer Res 1972 32: 1803–1808

    CAS  PubMed  Google Scholar 

  12. Franklin TJ, Cook JM . The inhibition of nucleic acid synthesis by mycophenolic acid Biochem J 1969 113: 515–517

    Article  CAS  Google Scholar 

  13. 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

    CAS  PubMed  Google Scholar 

  14. 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: 1097–2002

    Article  Google Scholar 

  15. 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  Google Scholar 

  16. Mirkovich A, Eugui EM . Prevention of murine graft-versus-host disease (GVHD) by mycophenolate mofetil (CellCept) 9th International Congress of Immunology, San Francisco July 1995 426

  17. Mathew TH, for the Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group . A blinded, long-term, randomized multicenter study of mycophenolate mofetil in cadaveric renal transplantation Transplantation 1998 65: 1450–1454

    Article  CAS  Google Scholar 

  18. Atkinson K, Rarewell V, Storb R et al. Analysis of late infections after human bone marrow transplantation: role of genotypic nonidentity between marrow donor and recipient and of nonspecific suppressor cells in patients with chronic graft-versus-host disease Blood 1982 60: 714–720

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, University of Turin, Italy

    A Busca & EM Saroglia

  2. IRCCS Istituto ‘Giannina Gaslini’ Genova, Italy

    E Lanino & L Manfredini

  3. Department of Pediatrics, University of Milan, Monza, Italy

    C Uderzo & B Nicolini

  4. Department of Pediatrics, Padova, Italy

    C Messina

  5. Department of Pediatrics, Trieste, Italy

    M Rabusin

  6. Department of Clinical and Biological Sciences, University of Turin, Italy

    R Miniero

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  1. A Busca
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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 25, 1067–1071 (2000). https://doi.org/10.1038/sj.bmt.1702410

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