Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

CMV infections after hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 42, pages S70–S72 (2008)Cite this article

Abstract

CMV can cause disease in several different organs after SCT. Seropositivity remains a major risk factor for TRM in unrelated SCT patients. In a study using the EBMT registry, CMV-seropositive patients receiving seropositive unrelated donor grafts had improved survival and reduced TRM compared with those receiving seronegative grafts, and a similar result was found in a single center study. Preventive measures can be divided into prevention of a primary infection or recurrence of CMV (prophylaxis) or prevention of development of disease when a reactivation has occurred (preemptive therapy). The standard therapy for CMV pneumonia has been i.v. ganciclovir combined with high-dose Ig, but this standard has never been evaluated in a controlled study and more recent studies have questioned whether the addition of Ig improves outcome.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Nichols WG, Corey L, Gooley T, Davis C, Boeckh M . High risk of death due to bacterial and fungal infection among cytomegalovirus (CMV)-seronegative recipients of stem cell transplants from seropositive donors: evidence for indirect effects of primary CMV infection. J Infect Dis 2002; 185: 273–282.

    Article  Google Scholar 

  2. Ringden O, Schaffer M, Le Blanc K, Persson U, Hauzenberger D, Abedi MR et al. Which donor should be chosen for hematopoietic stem cell transplantation among unrelated HLA-A, -B, and -DRB1 genomically identical volunteers? Biol Blood Marrow Transplant 2004; 10: 128–134.

    Article  Google Scholar 

  3. Boeckh M, Nichols WG . The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood 2004; 103: 2003–2008.

    Article  CAS  Google Scholar 

  4. Bowden RA, Slichter SJ, Sayers MH, Mori M, Cays MJ, Meyers JD . Use of leukocyte-depleted platelets and cytomegalovirus-seronegative red blood cells for prevention of primary cytomegalovirus infection after marrow transplant. Blood 1991; 78: 246–250.

    CAS  PubMed  Google Scholar 

  5. Nichols WG, Price TH, Gooley T, Corey L, Boeckh M . Transfusion-transmitted cytomegalovirus infection after receipt of leukoreduced blood products. Blood 2003; 101: 4195–4200.

    Article  CAS  Google Scholar 

  6. Ljungman P, Larsson K, Kumlien G, Aschan J, Barkholt L, Gustafsson-Jernberg A et al. Leukocyte depleted, unscreened blood products give a low risk for CMV infection and disease in CMV seronegative allogeneic stem cell transplant recipients with seronegative stem cell donors. Scand J Infect Dis 2002; 34: 347–350.

    Article  Google Scholar 

  7. Bowden R, Cays M, Schoch G, Sayers M, Slichter S, Welk K et al. Comparison of filtered blood (FB) to seronegative blood products (SB) for prevention of cytomegalovirus (CMV) infection after marrow transplant. Blood 1995; 86: 3598–3603.

    CAS  PubMed  Google Scholar 

  8. Prentice HG, Gluckman E, Powles RL, Ljungman P, Milpied N, Fernandez Ranada JM et al. Impact of long-term acyclovir on cytomegalovirus infection and survival after allogeneic bone marrow transplantation. European Acyclovir for CMV Prophylaxis Study Group. Lancet 1994; 343: 749–753.

    Article  CAS  Google Scholar 

  9. Ljungman P, De La Camara R, Milpied N, Volin L, Russell CA, Webster A et al. A randomised study of valaciclovir as prophylaxis against CMV reactivation in allogeneic bone marrow transplant recipients. Blood 2002; 73: 930–936.

    Google Scholar 

  10. Winston DJ, Young JA, Pullarkat V, Papanicolaou GA, Vij R, Vance E et al. Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem-cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study. Blood 2008.

  11. Marty FM, Bryar J, Browne SK, Schwarzberg T, Ho VT, Bassett IV et al. Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis. Blood 2007; 110: 490–500.

    Article  CAS  Google Scholar 

  12. Reusser P, Einsele H, Lee J, Volin L, Rovira M, Engelhard D et al. Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood 2002; 99: 1159–1164.

    Article  CAS  Google Scholar 

  13. Einsele H, Reusser P, Bornhauser M, Kalhs P, Ehninger G, Hebart H et al. Oral valganciclovir leads to higher exposure to ganciclovir than intravenous ganciclovir in patients following allogeneic stem cell transplantation. Blood 2006; 107: 3002–3008.

    Article  CAS  Google Scholar 

  14. Nichols WG, Corey L, Gooley T, Drew WL, Miner R, Huang M et al. Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes. Blood 2001; 97: 867–874.

    Article  CAS  Google Scholar 

  15. Gerna G, Lilleri D, Zecca M, Alessandrino EP, Baldanti F, Revello MG et al. Rising antigenemia levels may be misleading in pre-emptive therapy of human cytomegalovirus infection in allogeneic hematopoietic stem cell transplant recipients. Haematologica 2005; 90: 526–533.

    PubMed  Google Scholar 

  16. Ljungman P, Deliliers GL, Platzbecker U, Matthes-Martin S, Bacigalupo A, Einsele H et al. Cidofovir for cytomegalovirus infection and disease in allogeneic stem cell transplant recipients. The Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Blood 2001; 97: 388–392.

    Article  CAS  Google Scholar 

  17. Cesaro S, Zhou X, Manzardo C, Buonfrate D, Cusinato R, Tridello G et al. Cidofovir for cytomegalovirus reactivation in pediatric patients after hematopoietic stem cell transplantation. J Clin Virol 2005; 34: 129–132.

    Article  CAS  Google Scholar 

  18. Kaptein SJ, Efferth T, Leis M, Rechter S, Auerochs S, Kalmer M et al. The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo. Antiviral Res 2006; 69: 60–69.

    Article  CAS  Google Scholar 

  19. Levi ME, Mandava N, Chan LK, Weinberg A, Olson JL . Treatment of multidrug-resistant cytomegalovirus retinitis with systemically administered leflunomide. Transpl Infect Dis 2006; 8: 38–43.

    Article  CAS  Google Scholar 

  20. Ehlert K, Groll AH, Kuehn J, Vormoor J . Treatment of refractory CMV-infection following hematopoietic stem cell transplantation with the combination of foscarnet and leflunomide. Klin Padiatr 2006; 218: 180–184.

    Article  CAS  Google Scholar 

  21. Boeckh M, Leisenring W, Riddell SR, Bowden RA, Huang ML, Myerson D et al. Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood 2003; 101: 407–414.

    Article  CAS  Google Scholar 

  22. Machado CM, Dulley FL, Boas LS, Castelli JB, Macedo MC, Silva RL et al. CMV pneumonia in allogeneic BMT recipients undergoing early treatment of pre-emptive ganciclovir therapy. Bone Marrow Transplant 2000; 26: 413–417.

    Article  CAS  Google Scholar 

  23. Reusser P, Riddell SR, Meyers JD, Greenberg PD . Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. Blood 1991; 78: 1373–1380.

    CAS  PubMed  Google Scholar 

  24. Krause H, Hebart H, Jahn G, Muller CA, Einsele H . Screening for CMV-specific T cell proliferation to identify patients at risk of developing late onset CMV disease. Bone Marrow Transplant 1997; 19: 1111–1116.

    Article  CAS  Google Scholar 

  25. Ljungman P . Would monitoring CMV immune responses allow improved control of CMV in stem cell transplant patients. J Clin Virol 2006; 35: 493–495.

    Article  CAS  Google Scholar 

  26. Gerna G, Lilleri D, Fornara C, Comolli G, Lozza L, Campana C et al. Monitoring of human cytomegalovirus-specific CD4 and CD8 T-cell immunity in patients receiving solid organ transplantation. Am J Transplant 2006; 6: 2356–2364.

    Article  CAS  Google Scholar 

  27. Lilleri D, Fornara C, Furione M, Zavattoni M, Revello MG, Gerna G . Development of human cytomegalovirus-specific T cell immunity during primary infection of pregnant women and its correlation with virus transmission to the fetus. J Infect Dis 2007; 195: 1062–1070.

    Article  Google Scholar 

  28. Cwynarski K, Ainsworth J, Cobbold M, Wagner S, Mahendra P, Apperley J et al. Direct visualization of cytomegalovirus-specific T-cell reconstitution after allogeneic stem cell transplantation. Blood 2001; 97: 1232–1240.

    Article  CAS  Google Scholar 

  29. Peggs K, Verfuerth S, Mackinnon S . Induction of cytomegalovirus (CMV)-specific T-cell responses using dendritic cells pulsed with CMV antigen: a novel culture system free of live CMV virions. Blood 2001; 97: 994–1000.

    Article  CAS  Google Scholar 

  30. Einsele H, Roosnek E, Rufer N, Sinzger C, Riegler S, Loffler J et al. Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood 2002; 99: 3916–3922.

    Article  CAS  Google Scholar 

  31. Szmania S, Galloway A, Bruorton M, Musk P, Aubert G, Arthur A et al. Isolation and expansion of cytomegalovirus-specific cytotoxic T lymphocytes to clinical scale from a single blood draw using dendritic cells and HLA-tetramers. Blood 2001; 98: 505–512.

    Article  CAS  Google Scholar 

  32. Grigoleit GU, Kapp M, Hebart H, Fick K, Beck R, Jahn G et al. Dendritic cell vaccination in allogeneic stem cell recipients: induction of human cytomegalovirus (HCMV)-specific cytotoxic T lymphocyte responses even in patients receiving a transplant from an HCMV-seronegative donor. J Infect Dis 2007; 196: 699–704.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

    P Ljungman

Authors
  1. P Ljungman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P Ljungman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ljungman, P. CMV infections after hematopoietic stem cell transplantation. Bone Marrow Transplant 42 (Suppl 1), S70–S72 (2008). https://doi.org/10.1038/bmt.2008.120

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2008.120

Keywords

This article is cited by

Search

Advanced search

Quick links