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:

Post-Transplant Events

Evaluation of a surveillance strategy for early detection of adenovirus by PCR of peripheral blood in hematopoietic SCT recipients: incidence and outcome

Abstract

Adenoviruses (AdV) have emerged as important causes of morbidity and mortality in patients after hematopoietic SCT (HSCT). Early diagnosis of the infection by detection of viral DNA may improve the prognosis. A surveillance strategy was evaluated for detection of AdV DNA by PCR in a prospective study of unselected allogeneic HSCT recipients. In parallel with a routine CMV surveillance program, plasma from 20 children and 77 adults was analyzed by quantitative PCR for detection of AdV DNA. In addition, in 12 unselected patients, the presence of AdV-specific T cells were analyzed by enzyme-linked immunosorbent spot (ELISPOT) at 1 to 3 months after transplantation. A total of 5 of 97 (5%) patients had detectable AdV DNA in peripheral blood. Only one patient had high titers and none developed AdV disease. BM as a source of stem cells and myelodysplastic syndrome as the indication for transplantation were independently associated with higher risk of acquiring AdV infection. AdV-specific T cells were detected in 7 (58%) of 12 patients. Although AdV DNA was found in peripheral blood by quantitative PCR in 5% of patients undergoing allogeneic HSCT, the present surveillance program did not have a significant effect on the clinical outcome.

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

Access options

Buy this article

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

Figure 1

Similar content being viewed by others

References

  1. Billings JL, Hertz MI, Wendt CH . Community respiratory virus infections following lung transplantation. Transpl Infect Dis 2001; 3: 138–148.

    Article  CAS  Google Scholar 

  2. Emovon OE, Lin A, Howell DN, Afzal F, Baillie M, Rogers J et al. Refractory adenovirus infection after simultaneous kidney-pancreas transplantation: successful treatment with intravenous ribavirin and pooled human intravenous immunoglobulin. Nephrol Dial Transplant 2003; 18: 2436–2438.

    Article  CAS  Google Scholar 

  3. Hale GA, Heslop HE, Krance RA, Brenner MA, Jayawardene D, Srivastava DK et al. Adenovirus infection after pediatric bone marrow transplantation. Bone Marrow Transplant 1999; 23: 277–282.

    Article  CAS  Google Scholar 

  4. Hierholzer JC . Adenoviruses in the immunocompromised host. Clin Microbiol Rev 1992; 5: 262–274.

    Article  CAS  Google Scholar 

  5. Howard DS, Phillips IG, Reece DE, Munn RK, Henslee-Downey J, Pittard M et al. Adenovirus infections in hematopoietic stem cell transplant recipients. Clin Infect Dis 1999; 29: 1494–1501.

    Article  CAS  Google Scholar 

  6. Mori K, Yoshihara T, Nishimura Y, Uchida M, Katsura K, Kawase Y et al. Acute renal failure due to adenovirus-associated obstructive uropathy and necrotizing tubulointerstitial nephritis in a bone marrow transplant recipient. Bone Marrow Transplant 2003; 31: 1173–1176.

    Article  CAS  Google Scholar 

  7. Munoz FM, Piedra PA, Demmler GJ . Disseminated adenovirus disease in immunocompromised and immunocompetent children. Clin Infect Dis 1998; 27: 1194–1200.

    Article  CAS  Google Scholar 

  8. Walls T, Shankar AG, Shingadia D . Adenovirus: an increasingly important pathogen in paediatric bone marrow transplant patients. Lancet Infect Dis 2003; 3: 79–86.

    Article  Google Scholar 

  9. Echavarria M, Forman M, van Tol MJ, Vossen JM, Charache P, Kroes AC . Prediction of severe disseminated adenovirus infection by serum PCR. Lancet 2001; 358: 384–385.

    Article  CAS  Google Scholar 

  10. Gustafson I, Lindblom A, Yun Z, Omar H, Engstrom L, Lewensohn-Fuchs I et al. Quantification of adenovirus DNA in unrelated donor hematopoietic stem cell transplant recipients. J Clin Virol 2008; 43: 79–85.

    Article  CAS  Google Scholar 

  11. Schilham MW, Claas EC, van Zaane W, Heemskerk B, Vossen JM, Lankester AC et al. High levels of adenovirus DNA in serum correlate with fatal outcome of adenovirus infection in children after allogeneic stem-cell transplantation. Clin Infect Dis 2002; 35: 526–532.

    Article  Google Scholar 

  12. Bhadri VA, Lee-Horn L, Shaw PJ . Safety and tolerability of cidofovir in high-risk pediatric patients. Transpl Infect Dis 2009; 11: 373–379.

    Article  CAS  Google Scholar 

  13. Chakrabarti S, Mautner V, Osman H, Collingham KE, Fegan CD, Klapper PE et al. Adenovirus infections following allogeneic stem cell transplantation: incidence and outcome in relation to graft manipulation, immunosuppression, and immune recovery. Blood 2002; 100: 1619–1627.

    Article  CAS  Google Scholar 

  14. Heemskerk B, Lankester AC, van Vreeswijk T, Beersma MF, Claas EC, Veltrop-Duits LA et al. Immune reconstitution and clearance of human adenovirus viremia in pediatric stem-cell recipients. J Infect Dis 2005; 191: 520–530.

    Article  CAS  Google Scholar 

  15. van Tol MJ, Claas EC, Heemskerk B, Veltrop-Duits LA, de Brouwer CS, van Vreeswijk T et al. Adenovirus infection in children after allogeneic stem cell transplantation: diagnosis, treatment and immunity. Bone Marrow Transplant 2005; 35 (Suppl 1): S73–S76.

    Article  Google Scholar 

  16. Feuchtinger T, Lucke J, Hamprecht K, Richard C, Handgretinger R, Schumm M et al. Detection of adenovirus-specific T cells in children with adenovirus infection after allogeneic stem cell transplantation. Br J Haematol 2005; 128: 503–509.

    Article  Google Scholar 

  17. Feuchtinger T, Matthes-Martin S, Richard C, Lion T, Fuhrer M, Hamprecht K et al. Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation. Br J Haematol 2006; 134: 64–76.

    Article  Google Scholar 

  18. Ljungman P, Ribaud P, Eyrich M, Matthes-Martin S, Einsele H, Bleakley M et al. Cidofovir for adenovirus infections after allogeneic hematopoietic stem cell transplantation: a survey by the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 2003; 31: 481–486.

    Article  CAS  Google Scholar 

  19. Atkinson K, Horowitz MM, Gale RP, Lee MB, Rimm AA, Bortin MM . Consensus among bone marrow transplanters for diagnosis, grading and treatment of chronic graft-versus-host disease. Committee of the International Bone Marrow Transplant Registry. Bone Marrow Transplant 1989; 4: 247–254.

    CAS  PubMed  Google Scholar 

  20. Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA 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  Google Scholar 

  21. Le Blanc K, Remberger M, Uzunel M, Mattsson J, Barkholt L, Ringden O . A comparison of nonmyeloablative and reduced-intensity conditioning for allogeneic stem-cell transplantation. Transplantation 2004; 78: 1014–1020.

    Article  CAS  Google Scholar 

  22. Feuchtinger T, Lang P, Hamprecht K, Schumm M, Greil J, Jahn G et al. Isolation and expansion of human adenovirus-specific CD4+ and CD8+ T cells according to IFN-gamma secretion for adjuvant immunotherapy. Exp Hematol 2004; 32: 282–289.

    Article  CAS  Google Scholar 

  23. Baldwin A, Kingman H, Darville M, Foot AB, Grier D, Cornish JM et al. Outcome and clinical course of 100 patients with adenovirus infection following bone marrow transplantation. Bone Marrow Transplant 2000; 26: 1333–1338.

    Article  CAS  Google Scholar 

  24. Bruno B, Gooley T, Hackman RC, Davis C, Corey L, Boeckh M . Adenovirus infection in hematopoietic stem cell transplantation: effect of ganciclovir and impact on survival. Biol Blood Marrow Transplant 2003; 9: 341–352.

    Article  Google Scholar 

  25. Flomenberg P, Babbitt J, Drobyski WR, Ash RC, Carrigan DR, Sedmak GV et al. Increasing incidence of adenovirus disease in bone marrow transplant recipients. J Infect Dis 1994; 169: 775–781.

    Article  CAS  Google Scholar 

  26. Lion T, Baumgartinger R, Watzinger F, Matthes-Martin S, Suda M, Preuner S et al. Molecular monitoring of adenovirus in peripheral blood after allogeneic bone marrow transplantation permits early diagnosis of disseminated disease. Blood 2003; 102: 1114–1120.

    Article  CAS  Google Scholar 

  27. Walls T, Hawrami K, Ushiro-Lumb I, Shingadia D, Saha V, Shankar AG . Adenovirus infection after pediatric bone marrow transplantation: is treatment always necessary? Clin Infect Dis 2005; 40: 1244–1249.

    Article  Google Scholar 

  28. Shields AF, Hackman RC, Fife KH, Corey L, Meyers JD . Adenovirus infections in patients undergoing bone-marrow transplantation. N Engl J Med 1985; 312: 529–533.

    Article  CAS  Google Scholar 

  29. Suparno C, Milligan DW, Moss PA, Mautner V . Adenovirus infections in stem cell transplant recipients: recent developments in understanding of pathogenesis, diagnosis and management. Leuk Lymphoma 2004; 45: 873–885.

    Article  Google Scholar 

  30. Kalpoe JS, van der Heiden PL, Barge RM, Houtzager S, Lankester AC, van Tol MJ et al. Assessment of disseminated adenovirus infections using quantitative plasma PCR in adult allogeneic stem cell transplant recipients receiving reduced intensity or myeloablative conditioning. Eur J Haematol 2007; 78: 314–321.

    Article  CAS  Google Scholar 

  31. Lankester AC, van Tol MJ, Claas EC, Vossen JM, Kroes AC . Quantification of adenovirus DNA in plasma for management of infection in stem cell graft recipients. Clin Infect Dis 2002; 34: 864–867.

    Article  CAS  Google Scholar 

  32. Yusuf U, Hale GA, Carr J, Gu Z, Benaim E, Woodard P et al. Cidofovir for the treatment of adenoviral infection in pediatric hematopoietic stem cell transplant patients. Transplantation 2006; 81: 1398–1404.

    Article  CAS  Google Scholar 

  33. Avivi I, Chakrabarti S, Milligan DW, Waldmann H, Hale G, Osman H et al. Incidence and outcome of adenovirus disease in transplant recipients after reduced-intensity conditioning with alemtuzumab. Biol Blood Marrow Transplant 2004; 10: 186–194.

    Article  Google Scholar 

  34. Myers GD, Krance RA, Weiss H, Kuehnle I, Demmler G, Heslop HE et al. Adenovirus infection rates in pediatric recipients of alternate donor allogeneic bone marrow transplants receiving either antithymocyte globulin (ATG) or alemtuzumab (Campath). Bone Marrow Transplant 2005; 36: 1001–1008.

    Article  CAS  Google Scholar 

  35. Rebello P, Cwynarski K, Varughese M, Eades A, Apperley JF, Hale G . Pharmacokinetics of CAMPATH-1H in BMT patients. Cytotherapy 2001; 3: 261–267.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank all patients, including guardians, for their involvement in the study. We are indebted to Karin Fransson and the staff of the SCT units for their dedication to the study and collection of specimens. We acknowledge the technical and scientific contributions of Annika Allard at the clinical virological laboratory at Umeå University Hospital, Sweden, and the staff at the virological laboratory at Karolinska University Hospital, Huddinge, Sweden. Grants were received from the Stockholm City Council/Karolinska Institutet and from the Swedish Children's Cancer Foundation.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L Öhrmalm.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Öhrmalm, L., Lindblom, A., Omar, H. et al. Evaluation of a surveillance strategy for early detection of adenovirus by PCR of peripheral blood in hematopoietic SCT recipients: incidence and outcome. Bone Marrow Transplant 46, 267–272 (2011). https://doi.org/10.1038/bmt.2010.86

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2010.86

Keywords

This article is cited by

Search

Quick links