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Adenovirus infection in children after allogeneic stem cell transplantation: diagnosis, treatment and immunity

Bone Marrow Transplantation volume 35, pages S73–S76 (2005)Cite this article

Summary:

Human adenoviruses (HAdV) are a frequent cause of potentially fatal infections in patients after allogeneic stem cell transplantation, especially in children. Monitoring of serum/plasma by real-time quantitative PCR is a sensitive tool for the recognition of patients at risk of a potentially fatal infection and for the evaluation of the efficacy of treatment. Data from a retrospective study and from a prospective study demonstrate that recovery of immunity after transplantation is essential for the elimination of HAdV infection. The feasibility of several approaches for the manipulation of immunity in the immunocompromised host to prevent a fatal course of the infection is discussed.

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References

  1. 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  PubMed  Google Scholar 

  2. Kojaoghlanian T, Flomenberg P, Horwitz MS . The impact of adenovirus infection on the immunocompromised host. Rev Med Virol 2003; 13: 155–171.

    Article  PubMed  Google Scholar 

  3. Horwitz MS . Adenoviruses. In: Knipe DM, Howley PM (eds). Fields’ Virology. Lippincott Williams & Wilkins: Philadelphia, 2001, pp 2301–2326.

    Google Scholar 

  4. Garnett CT, Erdman D, Xu W, Gooding LR . Prevalence and quantitation of species C adenovirus DNA in human mucosal lymphocytes. J Virol 2002; 76: 10608–10616.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Heemskerk B, Lankester AC, van Vreeswijk T et al. Immune reconstitution and clearance of human adenovirus viremia in pediatric stem-cell recipients. J Infect Dis 2005; 191, in press.

    Article  CAS  PubMed  Google Scholar 

  6. Lankester AC, van Tol MJD, Claas ECJ et al. Quantification of adenovirus DNA in plasma: a role in management of stem cell graft recipients. Clin Infect Dis 2002; 34: 864–867.

    Article  CAS  PubMed  Google Scholar 

  7. Schilham MW, Claas EC, van Zaane W 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  PubMed  Google Scholar 

  8. Lion T, Baumgartinger R, Watzinger F 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  PubMed  Google Scholar 

  9. Bordigoni P, Carret AS, Venard V et al. Treatment of adenovirus infections in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 2001; 32: 1290–1297.

    Article  CAS  PubMed  Google Scholar 

  10. Legrand F, Berrebi D, Houhou N et al. Early diagnosis of adenovirus infection and treatment with cidofovir after bone marrow transplantation in children. Bone Marrow Transplant 2001; 27: 621–626.

    Article  CAS  PubMed  Google Scholar 

  11. Hoffman JA, Shah AJ, Ross LA, Kapoor N . Adenoviral infections and a prospective trial of cidofovir in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2001; 7: 388–394.

    Article  CAS  PubMed  Google Scholar 

  12. Miyamura K, Hamaguchi M, Taji H et al. Successful ribavirin therapy for severe adenovirus hemorrhagic cystitis after allogeneic marrow transplant from close HLA donors rather than distant donors. Bone Marrow Transplant 2000; 25: 545–548.

    Article  CAS  PubMed  Google Scholar 

  13. Lankester AC, Heemskerk B, Claas EC et al. Effect of ribavirin on the plasma viral DNA load in patients with disseminating adenovirus infection. Clin Infect Dis 2004; 38: 1521–1525.

    Article  CAS  PubMed  Google Scholar 

  14. Schleuning M, Buxbaum-Conradi H, Jager G, Kolb HJ . Intravenous ribavirin for eradication of respiratory syncytial virus (RSV) and adenovirus isolates from the respiratory and/or gastrointestinal tract in recipients of allogeneic hematopoietic stem cell transplants. Hematol J 2004; 5: 135–144.

    Article  CAS  PubMed  Google Scholar 

  15. Morfin F, Dupuis-Girod S, Mundweiler S et al. In vitro susceptibility of adenovirus to antiviral drugs is species-dependent. Antiviral Ther 2005, in press.

  16. Olive M, Eisenlohr L, Flomenberg N et al. The adenovirus capsid protein hexon contains a highly conserved human CD4+ T-cell epitope. Hum Gene Ther 2002; 13: 1167–1178.

    Article  CAS  PubMed  Google Scholar 

  17. Leen AM, Sili U, Vanin EF et al. Conserved CTL epitopes on the adenovirus hexon protein expand subgroup cross-reactive and subgroup-specific CD8+ T cells. Blood 2004; 104: 2432–2440.

    Article  CAS  PubMed  Google Scholar 

  18. Burgert HG, Ruzsics Z, Obermeier S et al. Subversion of host defense mechanisms by adenoviruses. Curr Top Microbiol Immunol 2002; 269: 273–318.

    CAS  PubMed  Google Scholar 

  19. Hromas R, Cornetta K, Srour E et al. Donor leukocyte infusion as therapy of life-threatening adenoviral infections after T cell depleted bone marrow transplantation. Blood 1994; 84: 1689–1690.

    CAS  PubMed  Google Scholar 

  20. Chakrabarti S, Collingham KE, Fegan CD et al. Adenovirus infections following haematopoietic cell transplantation: is there a role for adoptive immunotherapy? Bone Marrow Transplant 2000; 26: 305–307.

    Article  CAS  PubMed  Google Scholar 

  21. Chakrabarti S, Mautner V, Osman H 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  PubMed  Google Scholar 

  22. Andre-Schmutz I, Le Deist F, Hacein-Bey-Abina S et al. Immune reconstitution without graft-versus-host disease after haemopoietic stem-cell transplantation: a phase 1/2 study. Lancet 2002; 360: 130–137.

    Article  PubMed  Google Scholar 

  23. Heemskerk B, Veltrop-Duits LA, van Vreeswijk T et al. Extensive cross-reactivity of CD4+ adenovirus-specific T cells: implications for immunotherapy and gene therapy. J Virol 2003; 77: 6562–6566.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Veltrop-Duits LA, Heemskerk B, Sombroek CC et al. Human CD4+ T cells preferentially recognize conserved peptides of the adenovirus hexon protein: consequences for immuno- and gene therapy (submitted).

  25. Regn S, Raffegerst S, Chen X et al. Ex vivo generation of cytotoxic T lymphocytes specific for one or two distinct viruses for the prophylaxis of patients receiving an allogeneic bone marrow transplant. Bone Marrow Transplant 2001; 27: 53–64.

    Article  CAS  PubMed  Google Scholar 

  26. Leen AM, Sili U, Savoldo B et al. Fiber-modified adenoviruses generate subgroup cross-reactive, adenovirus-specific cytotoxic T lymphocytes for therapeutic applications. Blood 2004; 103: 1011–1019.

    Article  CAS  PubMed  Google Scholar 

  27. Feuchtinger T, Lang P, Hamprecht K 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  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Paediatrics, Leiden University Medical Centre, Leiden, The Netherlands

    M J D van Tol, B Heemskerk, L A Veltrop-Duits, T van Vreeswijk, C C Sombroek, R M Egeler, A C Lankester & M W Schilham

  2. Department of Medical Microbiology, Leiden University Medical Centre, Leiden, The Netherlands

    E C J Claas, C S de Brouwer, A C M Kroes, M F C Beersma & E P A de Klerk

Authors
  1. M J D van Tol
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  2. E C J Claas
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  3. B Heemskerk
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  4. L A Veltrop-Duits
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  5. C S de Brouwer
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  6. T van Vreeswijk
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  7. C C Sombroek
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  8. A C M Kroes
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  9. M F C Beersma
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  10. E P A de Klerk
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  11. R M Egeler
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  12. A C Lankester
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  13. M W Schilham
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Correspondence to M J D van Tol.

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van Tol, M., Claas, E., Heemskerk, B. et al. Adenovirus infection in children after allogeneic stem cell transplantation: diagnosis, treatment and immunity. Bone Marrow Transplant 35 (Suppl 1), S73–S76 (2005). https://doi.org/10.1038/sj.bmt.1704852

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