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Cytomegalovirus DNAemia Detected with Real-Time Polymerase Chain Reaction in Hematopoietic Stem Cell Transplant Patients

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Abstract

Introduction

Cytomegalovirus (CMV) infections continue to cause significant morbidity and mortality in hematopoietic stem cell transplant (HSCT) recipients. Successful pre-emptive therapy in transplant patients depends on the availability of reliable diagnostic tests for CMV infections. The purpose of this retrospective study was to evaluate CMV DNA viral load, incidence of CMV disease and CMV seropositivity, risk factors and correlation between CMV DNA positivity and clinical course in HSCT patients.

Methods

Two hundred and twenty-five patients who underwent peripheral blood stem cell or bone marrow transplantation between June 2003 and April 2010 were included. A real-time polymerase chain reaction (RT-PCR) assay was used for CMV monitoring.

Results

Recipient median age was 42.5 years. CMV seropositivity was 95.6%. CMV DNA positivity determined by RT-PCR was 24.9% among the entire patient group. CMV DNA positivity with RT-PCR was found to be significantly higher in allogeneic transplant recipients than autologous transplant recipients (46.7% vs 14.0%; P < 0.0001). Gender, age, conditioning regimen, stem cell source, underlying disease and recipient and donor seropositivity (alone or paired) were not significant risk factors for CMV DNAemia. We did not observe any CMV end-organ disease.

Conclusion

CMV DNAemia was significantly higher in allogeneic transplant recipients than in autologous transplant patients. End-organ disease could be prevented with appropriate pre-emptive therapy.

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References

  1. Boeckh M, Nichols WG, Papanicolaou G, et al. Cytomegalovirus in hematopoietic stem cell transplant recipients: current status, known challenges, and future strategies. Biol Blood Marrow Transplant. 2003;9:543–58.

    Article  PubMed  Google Scholar 

  2. Leruez-Ville M, Ouachee M, Delarue R, et al. Monitoring cytomegalovirus infection in adult and pediatric bone marrow transplant recipients by a real-time PCR assay performed with blood plasma. J Clin Microbiol. 2003;41:2040–6.

    Article  PubMed  CAS  Google Scholar 

  3. Goodrich JM, Mori M, Gleaves CA, et al. Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N Engl J Med. 1991;325:1601–7.

    Article  PubMed  CAS  Google Scholar 

  4. Goodrich JM, Bowden RA, Fisher L, et al. Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant. Ann Intern Med. 1993;118:173–8.

    Article  PubMed  CAS  Google Scholar 

  5. de la Cruz-Vicente F, Perez-Romero P, Aguilar-Guisado M, et al. Differences in cytomegalovirus replication quantified using quantitative polymerase chain reaction and antigenemia after allogeneic stem cell transplantation. Transplant Proc. 2010;42:3230–1.

    Article  PubMed  Google Scholar 

  6. Farfan UM, Torres TJ, Vergara AA, et al. Comparison of real-time polymerase chain reaction and antigenemia assay to detect cytomegalovirus in pediatric transplants. Rev Chilena Infectol. 2011;28:113–7.

    Article  Google Scholar 

  7. Zhai WJ, Wei JL, Zhao MF, et al. Comparison between CMV quantitative PCR and CMV-pp 65 antigen test for detection of CMV infection in allogeneic hematopoietic stem cell transplantation. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009;17:1522–6.

    PubMed  CAS  Google Scholar 

  8. Choi SM, Lee DG, Lim J, et al. Comparison of quantitative cytomegalovirus real-time PCR in whole blood and pp 65 antigenemia assay: clinical utility of CMV real-time PCR in hematopoietic stem cell transplant recipients. J Korean Med Sci. 2009;24:571–8.

    Article  PubMed  Google Scholar 

  9. Gimeno C, Solano C, Latorre JC, et al. Quantification of DNA in plasma by an automated real-time PCR assay (cytomegalovirus PCR kit) for surveillance of active cytomegalovirus infection and guidance of preemptive therapy for allogeneic hematopoietic stem cell transplant recipients. J Clin Microbiol. 2008;46:3311–8.

    Article  PubMed  CAS  Google Scholar 

  10. Ljungman P, Hakki M, Boeckh M. Cytomegalovirus in hematopoietic stem cell transplant recipients. Hematol Oncol Clin North Am. 2011;25:151–69.

    Article  PubMed  Google Scholar 

  11. Meyers JD, Flournoy N, Thomas ED. Risk factors for cytomegalovirus infection after human marrow transplantation. J Infect Dis. 1986;153:478–88.

    Article  PubMed  CAS  Google Scholar 

  12. Patel SR, Ridwan RU, Ortin M. Cytomegalovirus reactivation in pediatric hemopoietic progenitors transplant: a retrospective study on the risk factors and the efficacy of treatment. J Pediatr Hematol Oncol. 2005;27:411–5.

    Article  PubMed  Google Scholar 

  13. Zaucha-Prazmo A, Wojcik B, Drabko K, Choma M, Kowalczyk JR. Cytomegalovirus (CMV) infections in children undergoing hematopoietic stem cell transplantation. Pediatr Hematol Oncol. 2005;22:271–6.

    Article  PubMed  Google Scholar 

  14. Ataman S, Colak D, Gunseren F, et al. Investigation of cytomegalovirus seroepidemiology in Antalya with a population-based cross-sectional study and review of related data in Turkey. Mikrobiyol Bul. 2007;41:545–55.

    PubMed  Google Scholar 

  15. Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol. 2010;20:202–13.

    Article  PubMed  Google Scholar 

  16. Peres RM, Costa CR, Andrade PD, et al. Surveillance of active human cytomegalovirus infection in hematopoietic stem cell transplantation (HLA sibling identical donor): search for optimal cutoff value by real-time PCR. BMC Infect Dis. 2010;10:147.

    Article  PubMed  Google Scholar 

  17. Emery V, Zuckerman M, Jackson G, et al. Management of cytomegalovirus infection in haemopoietic stem cell transplantation. Br J Haematol. 2013;162:25–39.

    Article  PubMed  CAS  Google Scholar 

  18. Nichols WG, Boeckh M. Recent advances in the therapy and prevention of CMV infections. J Clin Virol. 2000;16:25–40.

    Article  PubMed  CAS  Google Scholar 

  19. de la Camara R, Fernandez-Ranada JM. Increased incidence of CMV infection after allogeneic bone marrow transplantation from unrelated donors but doubts about an increase in CMV-associated disease. Bone Marrow Transplant. 1997;20:181.

    Article  PubMed  Google Scholar 

  20. Takami A, Mochizuki K, Asakura H, et al. High incidence of cytomegalovirus reactivation in adult recipients of an unrelated cord blood transplant. Haematologica. 2005;90:1290–2.

    PubMed  Google Scholar 

  21. Takenaka K, Gondo H, Tanimoto K, et al. Increased incidence of cytomegalovirus (CMV) infection and CMV-associated disease after allogeneic bone marrow transplantation from unrelated donors. The Fukuoka Bone Marrow Transplantation Group. Bone Marrow Transplant. 1997;19:241–8.

    Article  PubMed  CAS  Google Scholar 

  22. Yoon HS, Lee JH, Choi ES, et al. Cytomegalovirus infection in children who underwent hematopoietic stem cell transplantation at a single center: a retrospective study of the risk factors. Pediatr Transplant. 2009;13:898–905.

    Article  PubMed  Google Scholar 

  23. Walker CM, van Burik JA, De For TE, Weisdorf DJ. Cytomegalovirus infection after allogeneic transplantation: comparison of cord blood with peripheral blood and marrow graft sources. Biol Blood Marrow Transplant. 2007;13:1106–15.

    Article  PubMed  Google Scholar 

  24. Asano-Mori Y, Oshima K, Sakata-Yanagimoto M, et al. High-grade cytomegalovirus antigenemia after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2005;36:813–9.

    Article  PubMed  CAS  Google Scholar 

  25. Zaia JA. Prevention of cytomegalovirus disease in hematopoietic stem cell transplantation. Clin Infect Dis. 2002;35:999–1004.

    Article  PubMed  Google Scholar 

  26. Reusser P, Attenhofer R, Hebart H, et al. Cytomegalovirus-specific T-cell immunity in recipients of autologous peripheral blood stem cell or bone marrow transplants. Blood. 1997;89:3873–9.

    PubMed  CAS  Google Scholar 

  27. Emery VC, Sabin CA, Cope AV, et al. Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation. Lancet. 2000;355:2032–6.

    Article  PubMed  CAS  Google Scholar 

  28. Gentile G, Picardi A, Capobianchi A, et al. A prospective study comparing quantitative cytomegalovirus (CMV) polymerase chain reaction in plasma and pp 65 antigenemia assay in monitoring patients after allogeneic stem cell transplantation. BMC Infect Dis. 2006;6:167.

    Article  PubMed  Google Scholar 

  29. Yakushiji K, Gondo H, Kamezaki K, et al. Monitoring of cytomegalovirus reactivation after allogeneic stem cell transplantation: comparison of an antigenemia assay and quantitative real-time polymerase chain reaction. Bone Marrow Transplant. 2002;29:599–606.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

No funding or sponsorship was received for this study or publication of this article. Dr. Deniz Goren Sahin is the guarantor for this article and takes responsibility for the integrity of the work as a whole.

Conflict of interest

Deniz Goren Sahin, Eren Gunduz, Nilgun Kasifoglu, Olga Akay, Tercan Us and Zafer Gulbas declare that they have no conflicts of interest.

Compliance with ethics guidelines

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients prior to inclusion in the study.

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Authors and Affiliations

  1. Department of Hematology, School of Medicine, Eskisehir Osmangazi University, Meselik Campus, 26480, Eskisehir, Turkey

    Deniz Goren Sahin, Eren Gunduz & Olga Meltem Akay

  2. Department of Microbiology, School of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey

    Nilgun Kasifoglu & Tercan Us

  3. Bone Marrow Transplantation Center, Anadolu Health Center, Gebze, Turkey

    Zafer Gulbas

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  1. Deniz Goren Sahin
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  2. Eren Gunduz
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  3. Nilgun Kasifoglu
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  4. Olga Meltem Akay
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  5. Tercan Us
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  6. Zafer Gulbas
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Correspondence to Deniz Goren Sahin.

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Sahin, D.G., Gunduz, E., Kasifoglu, N. et al. Cytomegalovirus DNAemia Detected with Real-Time Polymerase Chain Reaction in Hematopoietic Stem Cell Transplant Patients. Adv Ther 30, 784–791 (2013). https://doi.org/10.1007/s12325-013-0049-9

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  • DOI: https://doi.org/10.1007/s12325-013-0049-9

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