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A survey on incidence and management of adenovirus infection after allogeneic HSCT

Bone Marrow Transplantation volume 54, pages 1275–1280 (2019)Cite this article

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Abstract

To determine the current practices on the management of Adenovirus (ADV) infection after allogenic stem cell transplantation, a survey was undertook among EBMT centres. The response rate was 20% (91/446): 46% were adult, 44% were paediatric and 10% were mixed centres, respectively. The overall incidence of ADV infection was 7.1%: 4.1% in adult, 15.4% in paediatric, and 3.6% in mixed population. The determination of ADV-DNA in biological samples was used in 96% of centres; 58% of them monitored asymptomatic patients with a frequency of twice a week in 9%, once a week in 45%, every two weeks in 4% of centres. The treatment of ADV infection was mainly based on the administration of cidofovir (87%), being the schedule of 5 mg/kg/week with probenecid the most used, and the reduction of immunosuppression (84%). The threshold of ADV-DNAemia to start cidofovir in high-risk patients was most frequently >1000 copies/ml. Innovative treatments, such as brincidofovir and adoptive ADV-cytotoxic-T-lymphocytes, were used in 27% and 20% of centres, respectively. Almost all responding centres consider ADV infection serious enough to deserve testing asymptomatic or symptomatic patients. Cidofovir and reduction of immunosuppression represent the main therapeutic options but one fourth of responding centres experimented novel therapies.

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References

  1. Rowe WP, Huebner RJ, Gilmore LK, et al. Isolation of a cytopathogenic agent from human adenoids undergoing spontaneous degeneration in tissue culture. Proc Soc Exp Biol Med. 1953;84:570–3.

    Article  CAS  Google Scholar 

  2. 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 

  3. Heim A. Advances in the management of disseminated adenovirus disease in stem cell transplant recipients: impact of adenovirus load (DNAemia) testing. Expert Rev Anti Infect Ther. 2011;9:943–5.

    Article  Google Scholar 

  4. 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;102:1114–20.

    Article  CAS  Google Scholar 

  5. Öhrmalm L, Lindblom A, Omar H, Norbeck O, Gustafson I, Lewensohn-Fuchs I, Johansson JE, Brune M, Ljungman P, Broliden K. 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. 2011;46:267–72.

    Article  Google Scholar 

  6. La Rosa AM, Champlin RE, Mirza N, Gajewski J, Giralt S, Rolston KV, et al. Adenovirus infections in adult recipients of blood and marrow transplants. Clin Infect Dis. 2001;32:871–6.

    Article  Google Scholar 

  7. Howard DS, Phillips IG, Reece DE, Munn RK, Henslee-Downey I, Pittard M, et al. Adenovirus infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 1999;29:1494–501.

    Article  CAS  Google Scholar 

  8. 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;26:1333–8.

    Article  CAS  Google Scholar 

  9. Runde V, Ross S, Trenschel R, Lagemann E, Basu O, Renzing-Kohler K, et al. Adenoviral infection after allogeneic stem cell transplantation (SCT): report on 130 patients from a single SCT unit involved in a prospective multicenter surveillance study. Bone Marrow Transplant. 2001;28:51–57.

    Article  CAS  Google Scholar 

  10. Robin M, Marque-Juillet S, Scieux C, Peffault de Latour R, Ferry C, Rocha V, et al. Disseminated adenovirus infections after allogeneic hematopoietic stem cell transplantation: incidence, risk factors and outcome. Haematologica. 2007;92:1254–7.

    Article  Google Scholar 

  11. Symeonidis N, Jakubowski A, Pierre-Louis S, Jaffe D, Pamer E, Sepkowitz K, et al. Invasive adenoviral infections in T-cell-depleted allogeneic hematopoietic stem cell transplantation: high mortality in the era of cidofovir. Transpl Infect Dis. 2007;9:108–13.

    Article  CAS  Google Scholar 

  12. 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;100:1619–27.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Lee YJ, Chung D, Xiao K, Papadopoulos EB, Barker JN, Small TN, et al. Adenovirus viremia and disease: comparison of T cell-depleted and conventional hematopoietic stem cell transplantation recipients from a single institution. Biol Blood Marrow Transplant. 2013;19:387–92.

    Article  Google Scholar 

  15. 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;36:1001–8.

    Article  CAS  Google Scholar 

  16. Matthes-Martin S, Feuchtinger T, Shaw PJ, Engelhard D, Hirsch HH, Cordonnier C, Ljungman P. The fourth European Conference on Infections in Leukemia. European guidelines for diagnosis and treatment of adenovirus infection in leukemia and stem cell transplantation: summary of ECIL‐4 (2011). Transpl Infect Dis. 2012;14:555–63.

    Article  CAS  Google Scholar 

  17. 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;102:1114–20.

    Article  CAS  Google Scholar 

  18. Geyeregger R, Freimuller C, Stemberger J, Artwohl M, Witt V, Lion T, et al. First-in-man clinical results with good manufacturing practice (GMP)-compliant polypeptide-expanded adenovirus-specific T cells after haploidentical hematopoietic stem cell transplantation. J Immunother. 2014;37:245–9.

    Article  CAS  Google Scholar 

  19. Lee YL, Prockop SE, Papanicolaou G. Approach to adenovirus infections in the setting of hematopoietic cell transplantation. Curr Opin Infect Dis. 2017;30:377–87.

    Article  Google Scholar 

  20. Kerensky T, Hasan A, Schain D, Trikha G, Liu GC, Rand K, et al. Histopathologic resolution of adult liver transplantation adenovirus hepatitis with cidofovir and intravenous immunoglobulin: a case report. Transplant Proc. 2013;45:293–6.

    Article  CAS  Google Scholar 

  21. 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. 2013;18:2436–8.

    Article  Google Scholar 

  22. Voigt S, Pochon C, Rao K, et al. Incidence of adenovirus infections in pediatric and aldult allogeneic hematopoietic cell transplant recipeint inEurope. Bone Marrow Transplant. 2018;S1:83–84.

    Google Scholar 

  23. Hill JA, Mayer BT, Xie H, Leisenring WM, Huang ML, Stevens-Ayers T, et al. The cumulative burden of double-stranded DNA virus detection after allogeneic HSCT is associated with increased mortality. Blood. 2017;129:2316–25.

    Article  CAS  Google Scholar 

  24. Lion T, Kosulin K, Landlinger C, Rauch M, Preuner S, Jugovic D, et al. Monitoring of adenovirus load in stool by real-time PCR permits early detection of impending invasive infection in patients after allogeneic stem cell transplantation. Leukemia. 2010;24:706–14.

    Article  CAS  Google Scholar 

  25. Kosulin K, Geiger E, Vecsei A, et al. Persistence and reactivation of human adenoviruses in the gastrointestinal tract. Clin Microbiol Infect. 2016;22:381. e381‐388

    Article  Google Scholar 

  26. van Maarseveen NM, Wessels E, de Brouwer CS, Vossen AC, Claas EC. Diagnosis of viral gastroenteritis by simultaneous detection of Adenovirus group F, Astrovirus, Rotavirus group A, Norovirus genogroups I and II, and Sapovirus in two internally controlled multiplex real-time PCR assays. J Clin Virol. 2010;49:205–10.

    Article  Google Scholar 

  27. Pillet S, Lardeux M, Dina J, Grattard F, Verhoeven P, Le Goff J, Vabret A, Pozzetto B. Comparative evaluation of six commercialized multiplex PCR kits for the diagnosis of respiratory infections. PLoS One. 2013;8:e72174.

    Article  CAS  Google Scholar 

  28. Cox GJ, Matsui SM, Lo RS, et al. Etiology and outcome of diarrhea after marrow transplantation (a prospective study). Gastroenterology. 1994;107:1398–407.

    Article  CAS  Google Scholar 

  29. Troussard X, Bauduer F, Gallet E, et al. Virus recovery from stools of patients undergoing bone marrow transplantation. Bone Marrow Transplant. 1993;12:573–6.

    CAS  PubMed  Google Scholar 

  30. Chakrabarti S, Collingham KE, Stevens RH, Pillay D, Fegan CD, Milligan DW. Isolation of viruses from stools in stem cell transplant recipients (a prospective surveillance study). Bone Marrow Transplant. 2000;25:277–82.

    Article  CAS  Google Scholar 

  31. Kampmann B, Cubitt D, Walls T, et al. Improved outcome for children with disseminated adenoviral infection following allogeneic stem cell transplantation. Br J Haematol. 2005;130:595–603.

    Article  CAS  Google Scholar 

  32. Feuchtinger T, Lücke J, Hamprecht K, et al. Detection of adenovirus-specific T cells in children with adenovirus infection after allogeneic stem cell transplantation. Br J Haematol. 2005;128:503–9.

    Article  Google Scholar 

  33. Hiwarkar P, Gaspar HB, Gilmour K, et al. Impact of viral reactivations in the era of pre-emptive antiviral drug therapy following allogeneic haematopoietic SCT in paediatric recipients. Bone Marrow Transplant. 2013;48:803–8.

    Article  CAS  Google Scholar 

  34. Ljungman P, Ribaud P, Eyrich 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;31:481–6.

    Article  CAS  Google Scholar 

  35. Yusuf U, Hale GA, Carr J, et al. Cidofovir for the treatment of adenoviral infection in pediatric hematopoietic stem cell transplant patients. Transplantation. 2006;81:1398–404.

    Article  CAS  Google Scholar 

  36. Neofytos D, Ojha A, Mookerjee B, et al. Treatment of adenovirus disease in stem cell transplant recipients with cidofovir. Biol Blood Marrow Transplant. 2007;13:74–81.

    Article  CAS  Google Scholar 

  37. Grimley MS, Chemaly RF, Englund JA, Kurtzberg J, Chittick G, Brundage TM, Bae A, Morrison ME, Prasad VK. 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  Google Scholar 

  38. Hiwarkar P, Kosulin K, Cesaro S, Mikulska M, Styczynski J, Wynn R, Lion T. Management of adenovirus infection in patients after haematopoietic stem cell transplantation: State-of-the-art and real-life current approach: a position statement on behalf of the Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation. Rev Med Virol. 2018;28:e1980.

    Article  Google Scholar 

  39. Tzannou I, Papadopoulou A, Naik S, 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 hematopoieticstem‐cell transplantation. J Clin Oncol. 2017;35:3547–57.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank all EBMT centres that contributed to the survey and the doctors and nurses at each EBMT centre for their dedication to patient assistance and health.

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Authors and Affiliations

  1. Pediatric Hematology Oncology, Azienda Ospedaliera Universitaria Integrata, Verona, Italy

    Simone Cesaro & Gloria Tridello

  2. Pediatric Onco-Hematology, City of Health and Science, Regina Margherita Children Hospital, Turin, Italy

    Massimo Berger

  3. Division of Infectious Diseases, University of Genova (DISSAL) and IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Malgorzata Mikulska

  4. Division of Infection and Immunity, University College London, London, UK

    Katherine Nora Ward

  5. Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Division of Hematology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden

    Per Ljungman & Steffie Van Der Werf

  6. Infectious Disease Working Party Data Office, University of Leiden, Leiden, The Netherlands

    Per Ljungman & Steffie Van Der Werf

  7. Pediatric Infectious Diseases, Hadassah Hebrew University Medical Center, Jerusalem, Israel

    Dina Averbuch

  8. Department of Pediatric Hematology and Oncology, University Hospital, Collegium Medicum UMK, Bydgoszcz, Poland

    Jan Styczynski

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  1. Simone Cesaro
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on behalf of Infectious Disease Working Party of EBMT

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Correspondence to Simone Cesaro.

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Cesaro, S., Berger, M., Tridello, G. et al. A survey on incidence and management of adenovirus infection after allogeneic HSCT. Bone Marrow Transplant 54, 1275–1280 (2019). https://doi.org/10.1038/s41409-018-0421-0

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  • DOI: https://doi.org/10.1038/s41409-018-0421-0

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