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:

Infections Post Transplant

Evaluation of the NucliSens CMV pp67 assay for detection and monitoring of human cytomegalovirus infection after allogeneic stem cell transplantation

Bone Marrow Transplantation volume 30, pages 181–187 (2002)Cite this article

Abstract

Preemptive treatment based on the sensitive detection of CMV-DNA has helped to reduce HCMV-related mortality after allogeneic stem cell transplantation (SCT). Detection of active viral replication might help to better predict HCMV disease. In this study, 33 recipients at risk for HCMV infection after allogeneic SCT were prospectively monitored 1×/week for active HCMV infection by NASBA, whole blood DNA-PCR and virus culture assays. Preemptive antiviral therapy was initiated after the second positive PCR result, while NASBA results were not considered for clinical decision-making. Overall, a high agreement between PCR and NASBA on a per sample (85.3%) and per patient (87.9%) level was demonstrated. HCMV DNA titers in the blood were found to be higher in PCR+/NASBA+ compared to PCR+/NASBA− samples (P < 0.01). None of the NASBA-negative patients developed HCMV disease. Sixteen of 18 patients receiving PCR-based preemptive therapy were also found NASBA positive. There was no difference between the assays for the time to the first positive test result. However, the time to the first negative test result upon initiation of antiviral therapy was significantly shorter for the NASBA assay (P = 0.002), indicating a high positive predictive value to assess the efficacy of antiviral therapy. Three patients developed late-onset HCMV disease, all of whom were found to be PCR and NASBA positive. In conclusion, the data presented clearly demonstrate the value of patient monitoring using the NASBA assay to early diagnose active HCMV infection and to assess the efficacy of antiviral therapy in high risk patients after allogeneic SCT. A prospective comparison of PCR-based vs NASBA-based preemptive therapy is ongoing.

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
Figure 3

Similar content being viewed by others

References

  1. Emanuel D, Cunningham L, Jules-Elysee K et al. Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin Ann Intern Med 1988 109: 777 782

    Article  CAS  PubMed  Google Scholar 

  2. 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 

  3. Meyers JD, Flournoy N, Thomas ED . Risk factors for cytomegalovirus infection after human bone marrow transplantation J Infect Dis 1998 153: 478 488

    Article  Google Scholar 

  4. Reed EC, Bowden R, Dandliker PS et al. Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplantation Ann Intern Med 1998 109: 783 788

    Article  Google Scholar 

  5. Boeckh M, Bowden R, Gooley TA et al. Successful modification of a pp65 antigenemia-based early treatment strategy for prevention of cytomegalovirus disease in allogeneic marrow transplant recipients (letter) Blood 1999 93: 1781 1782

    CAS  PubMed  Google Scholar 

  6. Einsele H, Steidle M, Vallbracht A et al. Early occurence of HCMV infection after BMT as demonstrated by the PCR technique Blood 1991 77: 1104 1110

    CAS  PubMed  Google Scholar 

  7. Einsele H, Ehninger G, Steidle M et al. Polymerase chain reaction to evaluate antiviral therapy for cytomegalovirus disease Lancet 1991 338: 1170 1172

    Article  CAS  PubMed  Google Scholar 

  8. 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 

  9. Gor D, Sabin D, Prentice G et al. Longitudinal analysis in cytomegalovirus load in bone marrow transplant patients: relationship between peak virus load, donor/recipient serostatus, GVHD and disease Bone Marrow Transplant 1998 21: 597 605

    Article  CAS  PubMed  Google Scholar 

  10. Wolf DG, Spector S . Early diagnosis of human cytomegalovirus disease in transplant recipients by DNA amplification in plasma Transplantation 1993 56: 330 334

    Article  CAS  PubMed  Google Scholar 

  11. Einsele H, Hebart H, Kauffmann 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 

  12. Li CR, Greenberg P, Gilbert MJ et al. Recovery of HLA-restricted cytomegalovirus (CMV)-specific T-cell responses after allogeneic bone marrow transplant: correlation with CMV disease and effect of ganciclovir prophylaxis Blood 1994 83: 1971 1979

    CAS  PubMed  Google Scholar 

  13. Hiyoshi M, Tagawa S, Takubo T et al. Evaluation of AMPLICOR CMV test for direct detection of cytomegalovirus in plasma specimens J Clin Microbiol 1997 35: 2692 2694

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Sia IG, Wilson J, Espy MJ et al. Evaluation of the COBAS Amplicor CMV Monitor test for detection of viral DNA in specimens taken from patients after liver transplantation J Clin Microbiol 2000 38: 600 606

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Grundy JE, Ehrnst A, Einsele H et al. A three-center European external quality control study of PCR for detection of cytomegalovirus DNA in blood J Clin Microbiol 1996 34: 1166 1170

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Gerna G, Baldanti F, Middeldorp J et al. Clinical significance of expression of human cytomegalovirus pp67 late transcript in heart, lung and bone marrow transplant recipients as determined by nucleic acid sequence-based amplification J Clin Microbiol 1999 37: 902 911

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Kievits T, van Gemen B, van Strijp D et al. NASBA isothermal enzymatic in vitro nucleic acid amplification optimized for the diagnosis of HIV-1 infection J Virol Methods 1991 35: 273 286

    Article  CAS  PubMed  Google Scholar 

  18. Hebart H, Müller C, Löffler J et al. Monitoring of CMV infection: a comparison of PCR from whole blood, plasma-PCR, pp65-antigenemia and virus culture in patients after bone marrow transplantation Bone Marrow Transplant 1996 17: 861 868

    CAS  PubMed  Google Scholar 

  19. Ljungman P, Griffiths P . Definitions of cytomegalovirus infection and disease In: Michelson S, Plotkin SA (eds) Multidisciplinary Approach to Understanding Cytomegalovirus Disease Elsevier Science Publishers: Paris 1993 pp 233 237

    Google Scholar 

  20. Blok MJ, Goossens VJ, Vanherle SJ et al. Diagnostic value of monitoring CMV late pp67 mRNA expression in renal allograft recipients by nucleic-acid sequence-based amplification J Clin Microbiol 1998 36: 1341 1346

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Boom R, Sol CJ, Salimans MM et al. Rapid and simple method for purification of nucleic acids J Clin Microbiol 1990 28: 495 503

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Goodrich JM, Bowden R, Fisher L et al. Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant Ann Intern Med 1990 118: 173 178

    Article  Google Scholar 

  23. Emery VC, Cope AV, Bowen EF et al. The dynamics of human cytomegalovirus in vivo J Exp Med 1999 190: 177 182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Preiser W, Brauninger S, Schwerdtfeger R et al. Evaluation of diagnostic methods for the detection of cytomegalovirus in recipients of allogeneic stem cell transplants J Clin Virol 2001 20: 59 70

    Article  CAS  PubMed  Google Scholar 

  25. Saltzman RL, Quirk MR, Jordan MC . High levels of circulating cytomegalovirus DNA reflect visceral organ disease in viremic immunosuppressed patients other than marrow recipients J Clin Invest 1992 90: 1832 1838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the Deutsche Forschungsgemeinschaft (DFG), SFB 510, project B3, NucliSens pp67 test kits were kindly provided by Organon Teknika, The Netherlands.

Author information

Authors and Affiliations

  1. Abteilung II, Medizinische Klinik und Poliklinik, Tübingen, Germany

    H Hebart, T Rudolph, J Loeffler, T Ljubicic & H Einsele

  2. Abteilung für Medizinische Virologie, Hygieneinstitut, Tübingen, Germany

    G Jahn

  3. Department of Pathology, Free University Hospital, Amsterdam, The Netherlands

    J Middeldorp

Authors
  1. H Hebart
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T Rudolph
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Loeffler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Middeldorp
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T Ljubicic
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. G Jahn
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. H Einsele
    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

Hebart, H., Rudolph, T., Loeffler, J. et al. Evaluation of the NucliSens CMV pp67 assay for detection and monitoring of human cytomegalovirus infection after allogeneic stem cell transplantation. Bone Marrow Transplant 30, 181–187 (2002). https://doi.org/10.1038/sj.bmt.1703604

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1703604

Keywords

This article is cited by

Search

Advanced search

Quick links