Skip to main content

Advertisement

SpringerLink
Log in

Adenovirus Infection in Patients Undergoing Hematopoietic Stem Cell Transplantation

  • Review
  • Published:
Current Treatment Options in Infectious Diseases Aims and scope Submit manuscript

Abstract

Purpose of Review

Adenovirus (AdV) is a relatively common cause of viral infection in the general population, especially in childhood. In patients undergoing hematopoietic stem cell transplantation (HSCT), AdV infections can present as disseminated disease and can be life-threatening. Here, we present a review of AdV infection in the stem cell transplant setting, including AdV clinical presentation, epidemiology, and treatment, with a particular focus on novel virus-specific T cell (VST) therapy.

Recent Findings

Safe and effective treatments of AdV infection and disease are lacking; current therapies such as cidofovir are often accompanied by significant toxicity. Most recent advances in the treatment of AdV infection and disease have occurred in the realm of cytotoxic T cell therapy in which AdV is one of many viral targets. Notably, third-party VSTs have been observed to improve AdV viral load and improve disease symptoms without clear evidence for increased graft-versus-host disease risk.

Summary

While donor-derived and third-party AdV-targeted VSTs offer promise in the treatment of severe and disseminated AdV infection and disease, randomized-controlled trials are needed to demonstrate VST safety and efficacy in the stem cell transplant population. Despite encouraging findings, questions remain about ideal therapy candidates, donor sources, and combinations of viral targets for effective VST therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Human Adenovirus Working Group [Internet]. [cited 2023 Oct 1]. Available from: http://hadvwg.gmu.edu/

  2. Bennett JE, Dolin R, Blaser MJ, editors. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. 9th ed. Philadelphia, PA: Elsevier; 2020.

    Google Scholar 

  3. Lindemans CA, Leen AM, Boelens JJ. How I treat adenovirus in hematopoietic stem cell transplant recipients. Blood. 2010;116:5476–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Al-Heeti OM, Cathro HP, Ison MG. Adenovirus infection and transplantation. Transplantation. 2022;106:920–7.

    Article  CAS  PubMed  Google Scholar 

  5. Papanicolaou GA, Dvorak CC, Dadwal S, Maron G, Prasad VK, Giller R, et al. Practice patterns and incidence of adenovirus infection in allogeneic hematopoietic cell transplant recipients: multicenter survey of transplant centers in the United States. Transplant Infectious Dis. 2020;22:e13283.

    Article  Google Scholar 

  6. González-Vicent M, Verna M, Pochon C, Chandak A, Vainorius E, Brundage T, et al. Current practices in the management of adenovirus infection in allogeneic hematopoietic stem cell transplant recipients in Europe: The AdVance study. Eur J Haematol. 2019;102:210–7.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Kinchington PR, Romanowski EG, Jerold GY. Prospects for adenovirus antivirals. J Antimicrob Chemother. 2005;55:424–9.

    Article  CAS  PubMed  Google Scholar 

  8. Grimley MS, Chemaly RF, Englund JA, Kurtzberg J, Chittick G, Brundage TM, et al. Brincidofovir for asymptomatic adenovirus viremia in pediatric and adult allogeneic hematopoietic cell transplant recipients: a randomized placebo-controlled phase II trial. Biol Blood Marrow Transplant. 2017;23:512–21.

    Article  CAS  PubMed  Google Scholar 

  9. • Motta CM, Keller MD, Bollard CM. Applications of virus-specific T cell therapies post-BMT. Seminars Hematol. 2023;60:10–9. Comprehensive review of the applications of T cell therapies as treatment for different infections including Adenovirus post-HSCT.

    Article  Google Scholar 

  10. • Galletta TJ, Lane A, Lutzko C, Leemhuis T, Cancelas JA, Khoury R, et al. Third-party and patient-specific donor-derived virus-specific T cells demonstrate similar efficacy and safety for management of viral infections after hematopoietic stem cell transplantation in children and young adults. Transplant Cellular Ther. 2023;29:305–10. Retrospective cohort study of adults and children who received third-party and donor-derived VSTs for refractory viral infections at a single institution.

    Article  CAS  Google Scholar 

  11. Basso S, Compagno F, Zelini P, Giorgiani G, Boghen S, Bergami E, et al. Harnessing T cells to control infections after allogeneic hematopoietic stem cell transplantation. Front Immunol. 2020;11:567531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tischer S, Priesner C, Heuft H-G, Goudeva L, Mende W, Barthold M, et al. Rapid generation of clinical-grade antiviral T cells: selection of suitable T-cell donors and GMP-compliant manufacturing of antiviral T cells. J Transl Med. 2014;12:336.

    Article  PubMed  PubMed Central  Google Scholar 

  13. • Pfeiffer T, Tzannou I, Wu M, Ramos C, Sasa G, Martinez C, et al. Posoleucel, an allogeneic, off-the-shelf multivirus-specific T-cell therapy, for the treatment of refractory viral infections in the post-HCT setting. Clin Cancer Res. 2023;29:324–30. Open-label, phase II study of off the shelf third-party VSTs for treatment of adults and children post-HSCT with refractory viral infections.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. •• Leen AM, Bollard CM, Mendizabal AM, Shpall EJ, Szabolcs P, Antin JH, et al. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood. 2013;121:5113–23. Multicenter phase I/II study of adults and children post-HSCT with refractory viral infections treated with third-party VSTs.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Leen AM, Christin A, Myers GD, Liu H, Cruz CR, Hanley PJ, et al. Cytotoxic T lymphocyte therapy with donor T cells prevents and treats adenovirus and Epstein-Barr virus infections after haploidentical and matched unrelated stem cell transplantation. Blood. 2009;114:4283–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Papadopoulou A, Gerdemann U, Katari UL, Tzannou I, Liu H, Martinez C, et al. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med. 2014;6:242ra83.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ma CKK, Blyth E, Clancy L, Simms R, Burgess J, Brown R, et al. Addition of varicella zoster virus-specific T cells to cytomegalovirus, Epstein-Barr virus and adenovirus tri-specific T cells as adoptive immunotherapy in patients undergoing allogeneic hematopoietic stem cell transplantation. Cytotherapy. 2015;17:1406–20.

    Article  CAS  PubMed  Google Scholar 

  18. Quach DH, Lulla P, Rooney CM. Banking on virus-specific T cells to fulfill the need for off-the-shelf cell therapies. Blood. 2023;141:877–85.

    Article  CAS  PubMed  Google Scholar 

  19. Tzannou I, Papadopoulou A, Naik S, Leung K, Martinez CA, Ramos CA, et al. Off-the-shelf virus-specific T cells to treat BK virus, human herpesvirus 6, cytomegalovirus, Epstein-Barr virus, and adenovirus infections after allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 2017;35:3547–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. •• Rubinstein JD, Zhu X, Leemhuis T, Pham G, Ray L, Emberesh S, et al. Virus-specific T cells for adenovirus infection after stem cell transplantation are highly effective and class II HLA restricted. Blood Adv. 2021;5:3309–21. Single-center phase I/II trial treating patients with ADV infection with either donor-derived or third-party VSTs.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. •• Feucht J, Opherk K, Lang P, Kayser S, Hartl L, Bethge W, et al. Adoptive T-cell therapy with hexon-specific Th1 cells as a treatment of refractory adenovirus infection after HSCT. Blood. 2015;125:1986–94. Single-center clinical trial of donor-derived VSTs for treatment of adults and children post-HSCT with ADV infection refractory to antiviral therapy over 14 days.

    Article  CAS  PubMed  Google Scholar 

  22. Qian C, Campidelli A, Wang Y, Cai H, Venard V, Jeulin H, et al. Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial. J Hematol Oncol. 2017;10:102.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gerdemann U, Katari UL, Papadopoulou A, Keirnan JM, Craddock JA, Liu H, et al. Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant. Mol Ther. 2013;21:2113–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    A. Friedland MD & T. M. Andermann MD, MPH

  2. Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    A. Friedland MD & T. M. Andermann MD, MPH

  3. Division of Infectious Diseases, Department of Medicine, Duke University, Durham, NC, USA

    J. A. Messina MD

Authors
  1. A. Friedland MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. A. Messina MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. M. Andermann MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

A.F., J.A.M., and T.M.A. wrote the main manuscript. A.F. created Table 1. All authors reviewed the manuscript.

Corresponding author

Correspondence to T. M. Andermann MD, MPH.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Friedland, A., Messina, J.A. & Andermann, T.M. Adenovirus Infection in Patients Undergoing Hematopoietic Stem Cell Transplantation. Curr Treat Options Infect Dis (2024). https://doi.org/10.1007/s40506-024-00275-0

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s40506-024-00275-0

Keywords

Search

Navigation