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Post-Transplant Complications

Increased risk of complicated CMV infection with the use of mycophenolate mofetil in allogeneic stem cell transplantation

Abstract

Mycophenolate mofetil (MMF) is increasingly used for prophylaxis and therapy of GVHD in allogeneic stem cell transplantation. In some recent reports of use of MMF in solid organ transplantation a high incidence of CMV disease has been described. We evaluated the frequency and course of active CMV infection in patients who received MMF compared to those who did not receive MMF after allogeneic stem cell transplantation. We retrospectively analyzed 48 adult patients who consecutively underwent unmanipulated allogeneic bone marrow (n = 15) or peripheral stem cell transplantation (n = 33) from HLA-compatible family donors (n = 30) or unrelated donors (n = 18) from February 1997 to September 2000 at our institution. Only patients who were evaluable for the first 100 days were included in this analysis. Sixteen patients received MMF post transplant (MMF+). CMV-antigenemia was monitored by CMV-pp65 antigen. CMV-antigenemia occurred in 14 patients and was virtually only observed in CMV-IgG+ recipients (13/23, 56%). CMV-IgG+/MMF+ patients developed a higher incidence of CMV-antigenemia (8/9, 89%) compared to the CMV-IgG+/MMF− patients (5/14, 35%; P < 0.05). Moreover, five of six patients with persistent or recurrent CMV-antigenemia received MMF. No patient in either group developed CMV disease or died of CMV-related complications. In multivariate analysis including MMF treatment, unrelated vs related donor, GVHD, CMV-serostatus of the donor and stem cell graft type, only MMF treatment was found to be a significant risk factor for both overall and complicated CMV infection.

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References

  1. Basara N, Blau W, Kiehl M et al. Myocophenolate 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 

  2. Basara N, Blau W, Römer M 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  PubMed  Google Scholar 

  3. Allison A, Eugui E . Preferential suppression of lymphocyte proliferation by mycophenolic acid and predicted long-term effects of mycophenolate mofetil in transplantation Transplant Proc 1994 26: 3205 3210

    CAS  PubMed  Google Scholar 

  4. Sarmiento J, Dockrell D, Schwab T et al. Mycophenolate mofetil increases cytomegalovirus invasive organ disease in renal transplant patients Clin Transplant 2000 14: 136 138

    Article  CAS  PubMed  Google Scholar 

  5. ter Meulen C, Wetzels J, Hilsbrands L . 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 

  6. Moreso F, Seron D, Morales J et al. Incidence of leukopenia and cytomegalovirus disease in kidney transplants treated with mycophenolate mofetil combined with low cyclosporine and steroid doses Clin Transplant 1998 12: 198 205

    CAS  PubMed  Google Scholar 

  7. Glucksberg H, Storb R, Fefer A et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors Transplantation 1974 18: 295 304

    Article  CAS  PubMed  Google Scholar 

  8. van der Bij W, Torensma R, van Son W et al. Rapid immunodiagnosis of active cytomegalovirus infection by monoclonal antibody staining of blood leucocytes J Med Virol 1988 25: 179 188

    Article  CAS  PubMed  Google Scholar 

  9. Miller W, Flynn P, McCullough J et al. Cytomegalovirus infection after bone marrow transplantation: an association with acute graft-versus-host disease Blood 1986 67: 1162 1167

    CAS  PubMed  Google Scholar 

  10. Meyers J, Flournoy N, Thomas E . Risk factors for cytomegalovirus infection after human marrow transplantation J Infect Dis 1986 153: 478 488

    Article  CAS  PubMed  Google Scholar 

  11. Kröger N, Zabelina T, Krüger W et al. Patient cytomegalovirus seropositivity with or without reactivation is the most important prognostic factor for survival and treatment-related mortality in stem cell transplantation from unrelated donors using pretransplant in vivo T-cell depletion with anti-thymocyte globulin Br J Haematol 2001 113: 1060 1071

    Article  PubMed  Google Scholar 

  12. Trenschel R, Ross S, Hüsing J et al. Reduced risk of persisting cytomegalovirus pp65 antigenemia and cytomegalovirus interstitial pneumonia following allogeneic PBSCT Bone Marrow Transplant 2000 25: 665 672

    Article  CAS  PubMed  Google Scholar 

  13. Hebart H, Brugger W, Grigoleit U et al. Risk for cytomegalovirus disease in patients receiving polymerase chain reaction-based pre-emptive antiviral therapy after allogeneic stem cell transplantation Blood 2001 97: 2183 2185

    Article  CAS  PubMed  Google Scholar 

  14. McSweeney P, Niederwieser D, Shizuru J et al. Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects Blood 2001 97: 3390 3400

    Article  CAS  PubMed  Google Scholar 

  15. Bienvenu F, Thervet E, Bedrossian J et al. Development of cytomegalovirus resistance to ganciclovir after oral maintenance treatment in a renal transplant recipient Transplantation 1999 69: 182 184

    Article  Google Scholar 

Download references

Acknowledgements

We are grateful to Dr Martin Stanulla (Department of Pediatric Hematology and Oncology, Hannover Medical School) for critical reading of the manuscript and to Dr Heinz Geerlings (Department of Biometry, Hannover Medical School) for his support in the statistical analysis.

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Hambach, L., Stadler, M., Dammann, E. et al. Increased risk of complicated CMV infection with the use of mycophenolate mofetil in allogeneic stem cell transplantation. Bone Marrow Transplant 29, 903–906 (2002). https://doi.org/10.1038/sj.bmt.1703583

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