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.

  • Original Article
  • Published:

Viral Infections

Pre-emptive treatment of CMV DNAemia in paediatric stem cell transplantation: the impact of recipient and donor CMV serostatus on the incidence of CMV disease and CMV-related mortality

Bone Marrow Transplantation volume 31, pages 803–808 (2003)Cite this article

Summary:

Cytomegalovirus (CMV) DNAemia was detected by PCR in 30/125 (24%) consecutive paediatric patients undergoing allogeneic stem cell transplantation. All patients with CMV DNAemia received pre-emptive ganciclovir until two consecutive negative results were obtained. CMV-IgG-positive patients (R+) had a significantly increased risk of DNAemia as compared to CMV-IgG-negative (R−) patients (62% vs 8%) P<0.0001. The incidence of DNAemia was 71% (10/14) in R+ transplanted from seronegative donors (D−) compared to 54% (13/32) in those transplanted from seropositive donors (D+). Of 30 (40%) children with DNAemia, 12 developed CMV disease despite pre-emptive treatment. The overall incidence of disease was 0% (0/59) for R−/D−, 9% (3/23) for R+/D+, 7% (2/29) for R−/D+ and 57% (8/14) for R+/D−. In patients with DNAemia, 4/20 (20%) patients with D+ and 8/10 (80%) with D− became symptomatic. In the multivariate analysis of both groups, patients at risk (R+ and/or D+) and patients with DNAemia, a negative donor serostatus was the only factor associated with a significantly increased incidence of disease. Seven of 9 patients with lethal CMV disease had received CMV-IgG-negative grafts. The data suggest that in CMV seropositive recipients donor CMV seropositivity is associated with a reduced incidence of CMV disease and a favourable outcome following pre-emptive treatment.

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

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Bacigalupo A, Tedone E, Sanna MA et al. CMV infections following allogeneic BMT: risk factors, early treatment and correlation with transplant related mortality. Haematologica 1992; 77: 507–513.

    CAS  PubMed  Google Scholar 

  2. Humar A, Wood S, Lipton J et al. Effect of cytomegalovirus infection on 1-year mortality rates among recipients of allogeneic bone marrow transplants. Clin Infect Dis 1998; 26: 606–610.

    Article  CAS  PubMed  Google Scholar 

  3. Bacigalupo A, Tedone E, Isaza A et al. CMV-antigenemia after allogenic bone marrow transplantation: correlation of CMV-antigen positive cell numbers with transplant-related mortality. Bone Marrow Transplant 1995; 16: 155–161.

    CAS  PubMed  Google Scholar 

  4. Osarogiagbon RU, Defor TE, Weisdorf MA et al. CMV antigenemia following bone marrow transplantation: risk factors and outcomes [In Process Citation]. Biol Blood Marrow Transplant 2000; 6: 280–288.

    Article  CAS  PubMed  Google Scholar 

  5. Nguyen Q, Champlin R, Giralt S et al. Late cytomegalovirus pneumonia in adult allogeneic blood and marrow transplant recipients. Clin Infect Dis 1999; 28: 618–623.

    Article  CAS  PubMed  Google Scholar 

  6. Couriel D, Canosa J, Engler H et al. Early reactivation of cytomegalovirus and high risk of interstitial pneumonitis following T-depleted BMT for adults with hematological malignancies. Bone Marrow Transplant. 1996; 18: 347–353.

    CAS  PubMed  Google Scholar 

  7. Broers AE, van der Holt R, van Esser JW et al. Increased transplant-related mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depletd stem cell transplantation. Blood 2000; 95: 2240–2245.

    CAS  PubMed  Google Scholar 

  8. Craddock C, Szydlo RM, Dazzi et al. Cytomegalovirus seropositivity adversely influences outcome after T-depleted unrelated donor transplant patients with chronic myeloid leukaemia: the case for tailored graft-vs-host disease prophylaxis. Br J Haematol 2001; 112: 228–236.

    Article  CAS  PubMed  Google Scholar 

  9. Kroger N, Zabelina T, Kruger 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  CAS  PubMed  Google Scholar 

  10. Locatelli F, Percivalle E, Comoli P et al. Human cytomegalovirus (HCMV) infection in paediatric patients given allogeneic bone marrow transplantation: role of early antiviral treatment for HCMV antigenaemia on patients' outcome. Br J Haematol 1994; 88: 64–71.

    Article  CAS  PubMed  Google Scholar 

  11. Matthes-Martin S, Aberle SW, Peters C et al. CMV-viraemia during allogenic bone marrow transplantation in paediatric patients: association with survival and graft-vs-host disease. Bone Marrow Transplant 1998; 21 (Suppl 2): S53–S56.

    PubMed  Google Scholar 

  12. Einsele H, Ehninger G, Hebart H et al. Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration and side effects of antiviral therapy after bone marrow transplantation. Blood 1995; 86: 2815–2820.

    CAS  PubMed  Google Scholar 

  13. Einsele H, Hebart H, Kauffmann-Schneider C et al. Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection. Bone Marrow Transplant 2000; 25: 757–763.

    Article  CAS  PubMed  Google Scholar 

  14. Gratama JW, van Esser JW, Lamers CH et al. Tetramer based quantification of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in T-cell-depleted stem cell grafts and after transplantation may identify patients at risk for progressive CMV infection. Blood 2001; 98: 1358–1364.

    Article  CAS  PubMed  Google Scholar 

  15. Olive M, Simsek M, and Al Mufti S . Polymerase chain reaction assay for detection of human cytomegalovirus. J Clin Microbiol 1989; 27: 1238–1242.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Ljungman P, Griffiths PD, Paya C . Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 2002; 34: 1094–1097.

    Article  PubMed  Google Scholar 

  17. Prentice HG, Kho P . Clinical strategies for the management of cytomegalovirus infection and disease in allogeneic bone marrow transplant. Bone Marrow Transplant. 1997; 19: 135–142.

    Article  CAS  PubMed  Google Scholar 

  18. Bacigalupo A, Mordini N, Pitto A et al. Transplantation of HLA-mismatched CD34+ selected cells in patients with advanced malignancies: severe immunodeficiency and related complications. Br J Haematol 1997; 98: 760–766.

    Article  CAS  PubMed  Google Scholar 

  19. Foot AB, Pamphilon D, Caul EO et al. Cytomegalovirus in-fection in recipients of related and unrelated donor bone marrow transplants: no evidence of increased incidence in patients receiv-ing unrelated donor grafts. Br J Haematol 1998; 102: 671–677.

    Article  CAS  PubMed  Google Scholar 

  20. Mori T, Okamoto T, Matsuoka S et al. Risk-adapted pre-emptive therapy for cytomegalovirus disease in patients undergoing allogeneic bone marrow transplantation. Bone Marrow Transplant 2000; 25: 765–769.

    Article  CAS  PubMed  Google Scholar 

  21. Appleton AL, Sviland L, Peiris JS et al. Role of target organ infection with cytomegalovirus in the pathogenesis of graft-vs-host disease. Bone Marrow Transplant. 1995; 15: 557–561.

    CAS  PubMed  Google Scholar 

  22. Waldmann WJ, Knight DA, Adams PW . Cytolytic activity against allogeneic human endothelia: resistance of cytomegalovirus-infected cells and virally activated lysis of uninfected cells. Transplantation. 1998; 66: 67–77.

    Article  Google Scholar 

  23. Borchers AT, Perez R, Kaysen G, Ansari AA, Gershwin ME . Role of cytomegalovirus infection in allograft rejection: a review of possible mechanisms. Transplant Immunol 1999; 7: 75–82.

    Article  CAS  Google Scholar 

  24. Hagglund H, Bostrom L, Remberger M et al. Risk factors for acute graft-vs-host disease in 291 consecutive HLA-identical bone marrow transplant recipients. Bone Marrow Transplant 1995; 16: 747–753.

    CAS  PubMed  Google Scholar 

  25. Ljungman P, Aschan J, Azinge JN et al. Cytomegalovirus viraemia and specific T-helper cell responses as predictors of disease after allogeneic marrow transplantation. Br J Haematol 1993; 83: 118–124.

    Article  CAS  PubMed  Google Scholar 

  26. 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 

  27. Gor D, Sabin C, Prentice HG et al. Longitudinal fluctuations in cytomegalovirus load in bone marrow transplant patients: relationship between peak virus load donor/recipient serostatus, acute GVHD and CMV disease. Bone Marrow Transplant 1998; 21: 597–605.

    Article  CAS  PubMed  Google Scholar 

  28. Nichols WG, Corey L, Gooley TA et al. Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic stem cell transplantation: risk factors, cor-relation with DNA load, and outcomes. Blood 2001; 97: 867–874.

    Article  CAS  PubMed  Google Scholar 

  29. Ljungman P, Aschan J, Lewensohn-Fuchs I et al. Results of different strategies for reducing cytomegalovirus-associated mortality in allogeneic stem cell transplant recipients. Transplantation 1998; 66: 1330–1334.

    Article  CAS  PubMed  Google Scholar 

  30. Ljungman P, Brand R, Einsele H, Niederwieser D, Cordonnier C . Donor CMV serostatus influences outcome after unrelated donor stem cell transplantation; an EBMT megafile analysis. Blood 2001; 98: S2005.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. St. Anna Children's Hospital, Vienna, Austria

    S Matthes-Martin, A Lawitschka & C Peters

  2. Children's Cancer Research Institute, Vienna, Austria

    T Lion, G Fritsch & H Gadner

  3. Institute of Virology, University of Vienna, Vienna, Austria

    S W Aberle

  4. Department of Medical Statistics, University of Vienna, Vienna, Austria

    B Bittner & F Frommlet

Authors
  1. S Matthes-Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T Lion
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S W Aberle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G Fritsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Lawitschka
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. B Bittner
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F Frommlet
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H Gadner
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. C Peters
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matthes-Martin, S., Lion, T., Aberle, S. et al. Pre-emptive treatment of CMV DNAemia in paediatric stem cell transplantation: the impact of recipient and donor CMV serostatus on the incidence of CMV disease and CMV-related mortality. Bone Marrow Transplant 31, 803–808 (2003). https://doi.org/10.1038/sj.bmt.1703927

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703927

Keywords

This article is cited by

Search

Advanced search

Quick links