Adenovirus Infection in Allogeneic Stem Cell Transplantation

  • Susanne Matthes-Martin


Adenoviruses (HAdVs) are nonenveloped lytic DNA viruses with 67 different human serotypes. HAdV infection post transplant seems to be caused by endogenous viral reactivation in most cases. Quantitative HAdV PCR-diagnostics in peripheral blood (PB) samples has become gold standard. The incidence of HAdV viremia varies between 5 % and 68 %. The main risk factor for HAdV infection is prolonged immunosuppression, attributable either to in vivo or ex vivo T-cell depletion, prolonged lymphopenia, or to GvHD-associated immunosuppressive posttransplant therapy. For patients at risk, weekly PCR screening is recommended. The first symptoms of HAdV disease are frequently diarrhea, fever, elevated liver enzymes, and secondary pancytopenia. High levels of HAdV DNA in PB predicts disseminated HAdV disease, which is lethal despite virostatic treatment in most cases. Standard treatment for HAdV infections is cidofovir. The compound brincidofovir, an orally bioavailable lipid conjugate of cidofovir is currently being tested in several prospective trials. However, the recovery of HAdV-specific immunity seems to be critical for successful antiviral therapy. The transfer of HAdV-specific donor T cells in patients with HAdV viremia has been evaluated in several clinical phase I/II trials and preliminary data suggest that this approach may be feasible and effective.


Adenovirus Allogeneic stem cell transplantation Risk factors Cidofovir Brincidofovir Adoptive virus-specific T-cells 



We thank Thomas Lion who contributed to the diagnostic section. We would also like to thank Andreas Heitger, Rene Geyeregger, and Stephan Ladisch for carefully reading and editing the manuscript and Helmut Gadner for his continuous support—without him this work would not have been possible.


  1. 1.
    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(4):706–14.PubMedCrossRefGoogle Scholar
  2. 2.
    Benkö M, editor. Family adenovidriae. New York: Academic; 1999.Google Scholar
  3. 3.
    De Jong JC, Wermenbol AG, Verweij-Uijterwaal MW, Slaterus KW, Wertheim-Van Dillen P, Van Doornum GJ, et al. Adenoviruses from human immunodeficiency virus-infected individuals, including two strains that represent new candidate serotypes Ad50 and Ad51 of species B1 and D, respectively. J Clin Microbiol. 1999;37(12):3940–5.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Jones 2nd MS, Harrach B, Ganac RD, Gozum MM, Dela Cruz WP, Riedel B, et al. New adenovirus species found in a patient presenting with gastroenteritis. J Virol. 2007;81(11):5978–84.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Kidd AH, Jonsson M, Garwicz D, Kajon AE, Wermenbol AG, Verweij MW, et al. Rapid subgenus identification of human adenovirus isolates by a general PCR. J Clin Microbiol. 1996;34(3):622–7.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Xu W, McDonough MC, Erdman DD. Species-specific identification of human adenoviruses by a multiplex PCR assay. J Clin Microbiol. 2000;38(11):4114–20.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Echavarria M. Adenoviruses in immunocompromised hosts. Clin Microbiol Rev. 2008;21(4):704–15.PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Hara J, Okamoto S, Minekawa Y, Yamazaki K, Kase T. Survival and disinfection of adenovirus type 19 and enterovirus 70 in ophthalmic practice. Jpn J Ophthalmol. 1990;34(4):421–7.PubMedGoogle Scholar
  9. 9.
    Johansson C, Jonsson M, Marttila M, Persson D, Fan XL, Skog J, et al. Adenoviruses use lactoferrin as a bridge for CAR-independent binding to and infection of epithelial cells. J Virol. 2007;81(2):954–63.PubMedCrossRefGoogle Scholar
  10. 10.
    Leen AM, Bollard CM, Myers GD, Rooney CM. Adenoviral infections in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2006;12(3):243–51.PubMedCrossRefGoogle Scholar
  11. 11.
    Guidotti LG, Chisari FV. Noncytolytic control of viral infections by the innate and adaptive immune response. Annu Rev Immunol. 2001;19:65–91.PubMedCrossRefGoogle Scholar
  12. 12.
    Mayer A, Gelderblom H, Kumel G, Jungwirth C. Interferon-gamma-induced assembly block in the replication cycle of adenovirus 2: augmentation by tumour necrosis factor-alpha. Virology. 1992;187(1):372–6.PubMedCrossRefGoogle Scholar
  13. 13.
    Pasare C, Medzhitov R. Toll-like receptors: linking innate and adaptive immunity. Adv Exp Med Biol. 2005;560:11–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Shisler J, Duerksen-Hughes P, Hermiston TM, Wold WS, Gooding LR. Induction of susceptibility to tumor necrosis factor by E1A is dependent on binding to either p300 or p105-Rb and induction of DNA synthesis. J Virol. 1996;70(1):68–77.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Heemskerk B, van Vreeswijk T, Veltrop-Duits LA, Sombroek CC, Franken K, Verhoosel RM, et al. Adenovirus-specific CD4+ T cell clones recognizing endogenous antigen inhibit viral replication in vitro through cognate interaction. J Immunol. 2006;177(12):8851–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Olive M, Eisenlohr LC, Flomenberg P. Quantitative analysis of adenovirus-specific CD4+ T-cell responses from healthy adults. Viral Immunol. 2001;14(4):403–13.PubMedCrossRefGoogle Scholar
  17. 17.
    Smith CA, Woodruff LS, Kitchingman GR, Rooney CM. Adenovirus-pulsed dendritic cells stimulate human virus-specific T-cell responses in vitro. J Virol. 1996;70(10): 6733–40.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Onion D, Crompton LJ, Milligan DW, Moss PA, Lee SP, Mautner V. The CD4+ T-cell response to adenovirus is focused against conserved residues within the hexon protein. J Gen Virol. 2007;88(Pt 9):2417–25.PubMedCrossRefGoogle Scholar
  19. 19.
    Leen AM, Christin A, Khalil M, Weiss H, Gee AP, Brenner MK, et al. Identification of hexon-specific CD4 and CD8 T-cell epitopes for vaccine and immunotherapy. J Virol. 2008;82(1):546–54.PubMedCrossRefGoogle Scholar
  20. 20.
    Leen AM, Sili U, Vanin EF, Jewell AM, Xie W, Vignali D, et al. Conserved CTL epitopes on the adenovirus hexon protein expand subgroup cross-reactive and subgroup-specific CD8+ T cells. Blood. 2004;104(8):2432–40.PubMedCrossRefGoogle Scholar
  21. 21.
    Heemskerk B, Veltrop-Duits LA, van Vreeswijk T, ten Dam MM, Heidt S, Toes RE, et al. Extensive cross-reactivity of CD4+ adenovirus-specific T cells: implications for immunotherapy and gene therapy. J Virol. 2003;77(11):6562–6.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Leen AM, Sili U, Savoldo B, Jewell AM, Piedra PA, Brenner MK, et al. Fiber-modified adenoviruses generate subgroup cross-reactive, adenovirus-specific cytotoxic T lymphocytes for therapeutic applications. Blood. 2004;103(3):1011–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Smith CA, Woodruff LS, Rooney C, Kitchingman GR. Extensive cross-reactivity of adenovirus-specific cytotoxic T cells. Hum Gene Ther. 1998;9(10):1419–27.PubMedCrossRefGoogle Scholar
  24. 24.
    Tang J, Olive M, Pulmanausahakul R, Schnell M, Flomenberg N, Eisenlohr L, et al. Human CD8+ cytotoxic T cell responses to adenovirus capsid proteins. Virology. 2006;350(2):312–22.PubMedCrossRefGoogle Scholar
  25. 25.
    Lichtenstein DL, Toth K, Doronin K, Tollefson AE, Wold WS. Functions and mechanisms of action of the adenovirus E3 proteins. Int Rev Immunol. 2004;23(1–2):75–111.PubMedCrossRefGoogle Scholar
  26. 26.
    Schneider-Brachert W, Tchikov V, Merkel O, Jakob M, Hallas C, Kruse ML, et al. Inhibition of TNF receptor 1 internalization by adenovirus 14.7K as a novel immune escape mechanism. J Clin Invest. 2006;116(11):2901–13.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Tollefson AE, Toth K, Doronin K, Kuppuswamy M, Doronina OA, Lichtenstein DL, et al. Inhibition of TRAIL-induced apoptosis and forced internalization of TRAIL receptor 1 by adenovirus proteins. J Virol. 2001;75(19):8875–87.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Wold WS, Doronin K, Toth K, Kuppuswamy M, Lichtenstein DL, Tollefson AE. Immune responses to adenoviruses: viral evasion mechanisms and their implications for the clinic. Curr Opin Immunol. 1999;11(4):380–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Burgert HG, Ruzsics Z, Obermeier S, Hilgendorf A, Windheim M, Elsing A. Subversion of host defense mechanisms by adenoviruses. Curr Top Microbiol Immunol. 2002;269:273–318.PubMedGoogle Scholar
  30. 30.
    Gu L, Liu Z, Li X, Qu J, Guan W, Liu Y, et al. Severe community-acquired pneumonia caused by adenovirus type 11 in immunocompetent adults in Beijing. J Clin Virol. 2012;54(4):295–301.PubMedCrossRefGoogle Scholar
  31. 31.
    Rocholl C, Gerber K, Daly J, Pavia AT, Byington CL. Adenoviral infections in children: the impact of rapid diagnosis. Pediatrics. 2004;113(1 Pt 1):e51–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Savon C, Acosta B, Valdes O, Goyenechea A, Gonzalez G, Pinon A, et al. A myocarditis outbreak with fatal cases associated with adenovirus subgenera C among children from Havana City in 2005. J Clin Virol. 2008;43(2):152–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Sun B, He H, Wang Z, Qu J, Li X, Ban C, et al. Emergent severe acute respiratory distress syndrome caused by adenovirus type 55 in immunocompetent adults in 2013: a prospective observational study. Crit Care. 2014;18(4):456.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Chaberny IE, Schnitzler P, Geiss HK, Wendt C. An outbreak of epidemic keratoconjunctivtis in a pediatric unit due to adenovirus type 8. Infect Control Hosp Epidemiol. 2003;24(7):514–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Gerber SI, Erdman DD, Pur SL, Diaz PS, Segreti J, Kajon AE, et al. Outbreak of adenovirus genome type 7d2 infection in a pediatric chronic-care facility and tertiary-care hospital. Clin Infect Dis. 2001;32(5):694–700.PubMedCrossRefGoogle Scholar
  36. 36.
    Sivan AV, Lee T, Binn LN, Gaydos JC. Adenovirus-associated acute respiratory disease in healthy adolescents and adults: a literature review. Mil Med. 2007;172(11):1198–203.PubMedCrossRefGoogle Scholar
  37. 37.
    Berciaud S, Rayne F, Kassab S, Jubert C, Faure-Della Corte M, Salin F, et al. Adenovirus infections in Bordeaux University Hospital 2008-2010: clinical and virological features. J Clin Virol. 2012;54(4):302–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Gray GC, McCarthy T, Lebeck MG, Schnurr DP, Russell KL, Kajon AE, et al. Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004–2006. Clin Infect Dis. 2007;45(9):1120–31.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Garnett CT, Erdman D, Xu W, Gooding LR. Prevalence and quantitation of species C adenovirus DNA in human mucosal lymphocytes. J Virol. 2002;76(21):10608–16.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Garnett CT, Talekar G, Mahr JA, Huang W, Zhang Y, Ornelles DA, et al. Latent species C adenoviruses in human tonsil tissues. J Virol. 2009;83(6):2417–28.PubMedCrossRefGoogle Scholar
  41. 41.
    Roy S, Calcedo R, Medina-Jaszek A, Keough M, Peng H, Wilson JM. Adenoviruses in lymphocytes of the human gastro-intestinal tract. PLoS One. 2011;6(9):e24859.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Ebner K, Suda M, Watzinger F, Lion T. Molecular detection and quantitative analysis of the entire spectrum of human adenoviruses by a two-reaction real-time PCR assay. J Clin Microbiol. 2005;43(7):3049–53.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Terletskaia-Ladwig E, Leinmuller M, Schneider F, Meier S, Enders M. Laboratory approaches to the diagnosis of adenovirus infection depending on clinical manifestations. Infection. 2007;35(6):438–43.PubMedCrossRefGoogle Scholar
  44. 44.
    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(9279):384–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Heim A, Ebnet C, Harste G, Pring-Akerblom P. Rapid and quantitative detection of human adenovirus DNA by real-time PCR. J Med Virol. 2003;70(2):228–39.PubMedCrossRefGoogle Scholar
  46. 46.
    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(6):864–7.PubMedCrossRefGoogle Scholar
  47. 47.
    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(3):1114–20.PubMedCrossRefGoogle Scholar
  48. 48.
    Lu X, Erdman DD. Molecular typing of human adenoviruses by PCR and sequencing of a partial region of the hexon gene. Arch Virol. 2006;151(8):1587–602.PubMedCrossRefGoogle Scholar
  49. 49.
    Buckwalter SP, Teo R, Espy MJ, Sloan LM, Smith TF, Pritt BS. Real-time qualitative PCR for 57 human adenovirus types from multiple specimen sources. J Clin Microbiol. 2012;50(3): 766–71.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Aberle SW, Aberle JH, Steininger C, Matthes-Martin S, Pracher E, Popow-Kraupp T. Adenovirus DNA in serum of children hospitalized due to an acute respiratory adenovirus infection. J Infect Dis. 2003;187(2):311–4.PubMedCrossRefGoogle Scholar
  51. 51.
    Ronchi A, Doern C, Brock E, Pugni L, Sanchez PJ. Neonatal adenoviral infection: a seventeen year experience and review of the literature. J Pediatr. 2014;164(3):529–35 e1–4.Google Scholar
  52. 52.
    Wigger HJ, Blanc WA. Fatal hepatic and bronchial necrosis in adenovirus infection with thymic alymphoplasia. N Engl J Med. 1966;275(16):870–4.PubMedCrossRefGoogle Scholar
  53. 53.
    Lee YJ, Palomino-Guilen P, Babady NE, Lamson DM, St George K, Tang YW, et al. Disseminated adenovirus infection in cancer patients presenting with focal pulmonary consolidation. J Clin Microbiol. 2014;52(1):350–3.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Steiner I, Aebi C, Ridolfi Luthy A, Wagner B, Leibundgut K. Fatal adenovirus hepatitis during maintenance therapy for childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2008;50(3):647–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Christensen MS, Nielsen LP, Hasle H. Few but severe viral infections in children with cancer: a prospective RT-PCR and PCR-based 12-month study. Pediatr Blood Cancer. 2005;45(7): 945–51.PubMedCrossRefGoogle Scholar
  56. 56.
    Lo MS, Lee GM, Gunawardane N, Burchett SK, Lachenauer CS, Lehmann LE. The impact of RSV, adenovirus, influenza, and parainfluenza infection in pediatric patients receiving stem cell transplant, solid organ transplant, or cancer chemotherapy. Pediatr Transplant. 2013;17(2):133–43.PubMedCrossRefGoogle Scholar
  57. 57.
    Cavalli-Bjorkman N, Osby E, Lundin J, Kalin M, Osterborg A, Gruber A. Fatal adenovirus infection during alemtuzumab (anti-CD52 monoclonal antibody) treatment of a patient with fludarabine-refractory B-cell chronic lymphocytic leukemia. Med Oncol. 2002;19(4):277–80.PubMedCrossRefGoogle Scholar
  58. 58.
    Hough R, Chetwood A, Sinfield R, Welch J, Vora A. Fatal adenovirus hepatitis during standard chemotherapy for childhood acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2005;27(2):67–72.PubMedCrossRefGoogle Scholar
  59. 59.
    Ljungman P, Ehrnst A, Bjorkstrand B, Hellstrom E, Ingelman-Sundberg H, Juliusson G, et al. Lethal disseminated adenovirus type 1 infection in a patient with chronic lymphocytic leukemia. Scand J Infect Dis. 1990;22(5):601–5.PubMedCrossRefGoogle Scholar
  60. 60.
    Moyo SJ, Hanevik K, Blomberg B, Kommedal O, Nordbo SA, Maselle S, et al. Prevalence and molecular characterisation of human adenovirus in diarrhoeic children in Tanzania; a case control study. BMC Infect Dis. 2014;14:666.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Thomas PD, Pollok RC, Gazzard BG. Enteric viral infections as a cause of diarrhoea in the acquired immunodeficiency syndrome. HIV Med. 1999;1(1):19–24.PubMedCrossRefGoogle Scholar
  62. 62.
    Adeyemi OA, Yeldandi AV, Ison MG. Fatal adenovirus pneumonia in a person with AIDS and Burkitt lymphoma: a case report and review of the literature. AIDS Read. 2008;18(4):196–8. 201–2, 6–7.PubMedGoogle Scholar
  63. 63.
    Nebbia G, Chawla A, Schutten M, Atkinson C, Raza M, Johnson M, et al. Adenovirus viraemia and dissemination unresponsive to antiviral therapy in advanced HIV-1 infection. Aids. 2005;19(12):1339–40.PubMedCrossRefGoogle Scholar
  64. 64.
    Erard V, Huang ML, Ferrenberg J, Nguy L, Stevens-Ayers TL, Hackman RC, et al. Quantitative real-time polymerase chain reaction for detection of adenovirus after T cell-replete hematopoietic cell transplantation: viral load as a marker for invasive disease. Clin Infect Dis. 2007;45(8): 958–65.PubMedCrossRefGoogle Scholar
  65. 65.
    Breuer S, Rauch M, Matthes-Martin S, Lion T. Molecular diagnosis and management of viral infections in hematopoietic stem cell transplant recipients. Mol Diagn Ther. 2012;16(2):63–77.PubMedCrossRefGoogle Scholar
  66. 66.
    Jeulin H, Salmon A, Bordigoni P, Venard V. Diagnostic value of quantitative PCR for adenovirus detection in stool samples as compared with antigen detection and cell culture in haematopoietic stem cell transplant recipients. Clin Microbiol Infect. 2011;17(11):1674–80.PubMedCrossRefGoogle Scholar
  67. 67.
    Vabret A, Gouarin S, Joannes M, Barranger C, Petitjean J, Corbet S, et al. Development of a PCR-and hybridization-based assay (PCR Adenovirus Consensus) for the detection and the species identification of adenoviruses in respiratory specimens. J Clin Virol. 2004;31(2):116–22.PubMedCrossRefGoogle Scholar
  68. 68.
    Kroes AC, de Klerk EP, Lankester AC, Malipaard C, de Brouwer CS, Claas EC, et al. Sequential emergence of multiple adenovirus serotypes after pediatric stem cell transplantation. J Clin Virol. 2007;38(4):341–7.PubMedCrossRefGoogle Scholar
  69. 69.
    Lion T, Gaiger A, Henn T, Horth E, Haas OA, Geissler K, et al. Use of quantitative polymerase chain reaction to monitor residual disease in chronic myelogenous leukemia during treatment with interferon. Leukemia. 1995;9(8):1353–60.PubMedGoogle Scholar
  70. 70.
    Takayama R, Hatakeyama N, Suzuki N, Yamamoto M, Hayashi T, Ikeda Y, et al. Quantification of adenovirus species B and C viremia by real-time PCR in adults and children undergoing stem cell transplantation. J Med Virol. 2007;79(3):278–84.PubMedCrossRefGoogle Scholar
  71. 71.
    Zheng X, Lu X, Erdman DD, Anderson EJ, Guzman-Cottrill JA, Kletzel M, et al. Identification of adenoviruses in specimens from high-risk pediatric stem cell transplant recipients and controls. J Clin Microbiol. 2008;46(1):317–20.PubMedCrossRefGoogle Scholar
  72. 72.
    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(1):79–85.PubMedCrossRefGoogle Scholar
  73. 73.
    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(5):526–32.PubMedCrossRefGoogle Scholar
  74. 74.
    Mynarek M, Ganzenmueller T, Mueller-Heine A, Mielke C, Gonnermann A, Beier R, et al. Patient, virus, and treatment-related risk factors in pediatric adenovirus infection after stem cell transplantation: results of a routine monitoring program. Biol Blood Marrow Transplant. 2014;20(2):250–6.PubMedCrossRefGoogle Scholar
  75. 75.
    Srinivasan A, Klepper C, Sunkara A, Kang G, Carr J, Gu Z, et al. Impact of adenoviral stool load on adenoviremia in pediatric hematopoietic stem cell transplant recipients. Pediatr Infect Dis J. 2015;34(6):562–5.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Matthes-Martin S, Feuchtinger T, Shaw PJ, Engelhard D, Hirsch HH, Cordonnier C, et al. 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(6):555–63.PubMedCrossRefGoogle Scholar
  77. 77.
    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(5):1619–27.PubMedCrossRefGoogle Scholar
  78. 78.
    Kampmann B, Cubitt D, Walls T, Naik P, Depala M, Samarasinghe S, et al. Improved outcome for children with disseminated adenoviral infection following allogeneic stem cell transplantation. Br J Haematol. 2005;130(4):595–603.PubMedCrossRefGoogle Scholar
  79. 79.
    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(3):387–92.PubMedCrossRefGoogle Scholar
  80. 80.
    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(11): 1001–8.PubMedCrossRefGoogle Scholar
  81. 81.
    van Tol MJ, Kroes AC, Schinkel J, Dinkelaar W, Claas EC, Jol-van der Zijde CM, et al. Adenovirus infection in paediatric stem cell transplant recipients: increased risk in young children with a delayed immune recovery. Bone Marrow Transplant. 2005;36(1):39–50.PubMedCrossRefGoogle Scholar
  82. 82.
    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(9):1244–9.PubMedCrossRefGoogle Scholar
  83. 83.
    Bil-Lula I, Ussowicz M, Rybka B, Wendycz-Domalewska D, Ryczan R, Gorczynska E, et al. PCR diagnostics and monitoring of adenoviral infections in hematopoietic stem cell transplantation recipients. Arch Virol. 2010;155(12):2007–15.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Sive JI, Thomson KJ, Morris EC, Ward KN, Peggs KS. Adenoviremia has limited clinical impact in the majority of patients following alemtuzumab-based allogeneic stem cell transplantation in adults. Clin Infect Dis. 2012;55(10): 1362–70.PubMedCrossRefGoogle Scholar
  85. 85.
    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(3):186–94.PubMedCrossRefGoogle Scholar
  86. 86.
    Ohrmalm L, Lindblom A, Omar H, Norbeck O, Gustafson I, Lewensohn-Fuchs I, 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. 2011;46(2):267–72.PubMedCrossRefGoogle Scholar
  87. 87.
    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(2):108–13.PubMedCrossRefGoogle Scholar
  88. 88.
    Omar H, Yun Z, Lewensohn-Fuchs I, Perez-Bercoff L, Orvell C, Engstrom L, et al. Poor outcome of adenovirus infections in adult hematopoietic stem cell transplant patients with sustained adenovirus viremia. Transpl Infect Dis. 2010;12(5):465–9.PubMedCrossRefGoogle Scholar
  89. 89.
    Ganzenmueller T, Buchholz S, Harste G, Dammann E, Trenschel R, Heim A. High lethality of human adenovirus disease in adult allogeneic stem cell transplant recipients with high adenoviral blood load. J Clin Virol. 2011;52(1):55–9.PubMedCrossRefGoogle Scholar
  90. 90.
    Yilmaz M, Chemaly RF, Han XY, Thall PF, Fox PS, Tarrand JJ, et al. Adenoviral infections in adult allogeneic hematopoietic SCT recipients: a single center experience. Bone Marrow Transplant. 2013;48(9):1218–23.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Anderson EJ, Guzman-Cottrill JA, Kletzel M, Thormann K, Sullivan C, Zheng X, et al. High-risk adenovirus-infected pediatric allogeneic hematopoietic progenitor cell transplant recipients and preemptive cidofovir therapy. Pediatr Transplant. 2008;12(2):219–27.PubMedCrossRefGoogle Scholar
  92. 92.
    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 multi center surveillance study. Bone Marrow Transplant. 2001;28(1):51–7.PubMedCrossRefGoogle Scholar
  93. 93.
    de Pagter AP, Haveman LM, Schuurman R, Schutten M, Bierings M, Boelens JJ. Adenovirus DNA positivity in nasopharyngeal aspirate preceding hematopoietic stem cell transplantation: a very strong risk factor for adenovirus DNAemia in pediatric patients. Clin Infect Dis. 2009;49(10):1536–9.PubMedCrossRefGoogle Scholar
  94. 94.
    Hiwarkar P, Gaspar HB, Gilmour K, Jagani M, Chiesa R, Bennett-Rees N, 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(6):803–8.PubMedCrossRefGoogle Scholar
  95. 95.
    Myers GD, Bollard CM, Wu MF, Weiss H, Rooney CM, Heslop HE, et al. Reconstitution of adenovirus-specific cell-mediated immunity in pediatric patients after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2007;39(11):677–86.PubMedCrossRefGoogle Scholar
  96. 96.
    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(9):1254–7.PubMedCrossRefGoogle Scholar
  97. 97.
    Ruggeri A, Peffault de Latour R, Carmagnat M, Clave E, Douay C, Larghero J, et al. Outcomes, infections, and immune reconstitution after double cord blood transplantation in patients with high-risk hematological diseases. Transpl Infect Dis. 2011;13(5):456–65.PubMedCrossRefGoogle Scholar
  98. 98.
    Saliba RM, Rezvani K, Leen A, Jorgensen J, Shah N, Hosing C, et al. General and virus-specific immune cell reconstitution after double cord blood transplantation. Biol Blood Marrow Transplant. 2015;21(7):1284–90.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Sivaprakasam P, Carr TF, Coussons M, Khalid T, Bailey AS, Guiver M, et al. Improved outcome from invasive adenovirus infection in pediatric patients after hemopoietic stem cell transplantation using intensive clinical surveillance and early intervention. J Pediatr Hematol Oncol. 2007;29(2):81–5.PubMedCrossRefGoogle Scholar
  100. 100.
    Willemsen L, Jol-van der Zijde CM, Admiraal R, Putter H, Jansen-Hoogendijk AM, Ostaijen-Ten Dam MM, et al. Impact of serotherapy on immune reconstitution and survival outcomes after stem cell transplantations in children: thymoglobulin versus alemtuzumab. Biol Blood Marrow Transplant. 2015;21(3):473–82.PubMedCrossRefGoogle Scholar
  101. 101.
    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(4):520–30.PubMedCrossRefGoogle Scholar
  102. 102.
    Zandvliet ML, Falkenburg JH, van Liempt E, Veltrop-Duits LA, Lankester AC, Kalpoe JS, et al. Combined CD8+ and CD4+ adenovirus hexon-specific T cells associated with viral clearance after stem cell transplantation as treatment for adenovirus infection. Haematologica. 2010;95(11):1943–51.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Chakupurakal G, Onion D, Bonney S, Cobbold M, Mautner V, Moss P. HLA-peptide multimer selection of adenovirus-specific T cells for adoptive T-cell therapy. J Immunother. 2013;36(8):423–31.PubMedCrossRefGoogle Scholar
  104. 104.
    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(4): 503–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Geyeregger R, Freimuller C, Stevanovic S, Stemberger J, Mester G, Dmytrus J, et al. Short-term in-vitro expansion improves monitoring and allows affordable generation of virus-specific T-cells against several viruses for a broad clinical application. PLoS One. 2013;8(4):e59592.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    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(6):1494–501.PubMedCrossRefGoogle Scholar
  107. 107.
    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(4):245–9.PubMedCrossRefGoogle Scholar
  108. 108.
    Taniguchi K, Yoshihara S, Tamaki H, Fujimoto T, Ikegame K, Kaida K, et al. Incidence and treatment strategy for disseminated adenovirus disease after haploidentical stem cell transplantation. Ann Hematol. 2012;91(8):1305–12.PubMedCrossRefGoogle Scholar
  109. 109.
    Leruez-Ville M, Chardin-Ouachee M, Neven B, Picard C, Le Guinche I, Fischer A, et al. Description of an adenovirus A31 outbreak in a paediatric haematology unit. Bone Marrow Transplant. 2006;38(1):23–8.PubMedCrossRefGoogle Scholar
  110. 110.
    Mattner F, Sykora KW, Meissner B, Heim A. An adenovirus type F41 outbreak in a pediatric bone marrow transplant unit: analysis of clinical impact and preventive strategies. Pediatr Infect Dis J. 2008;27(5):419–24.PubMedCrossRefGoogle Scholar
  111. 111.
    Venard V, Carret A, Corsaro D, Bordigoni P, Le Faou A. Genotyping of adenoviruses isolated in an outbreak in a bone marrow transplant unit shows that diverse strains are involved. J Hosp Infect. 2000;44(1):71–4.PubMedCrossRefGoogle Scholar
  112. 112.
    Swartling L, Allard A, Torlen J, Ljungman P, Mattsson J, Sparrelid E. Prolonged outbreak of adenovirus A31 in allogeneic stem cell transplant recipients. Transpl Infect Dis. 2015;17:785–94.PubMedCrossRefGoogle Scholar
  113. 113.
    Veltrop-Duits LA, van Vreeswijk T, Heemskerk B, Thijssen JC, El Seady R, Jol-van der Zijde EM, et al. High titers of pre-existing adenovirus serotype-specific neutralizing antibodies in the host predict viral reactivation after allogeneic stem cell transplantation in children. Clin Infect Dis. 2011;52(12):1405–13.PubMedCrossRefGoogle Scholar
  114. 114.
    Guarner J, de Leon-Bojorge B, Lopez-Corella E, Ferebee-Harris T, Gooding L, Garnett CT, et al. Intestinal intussusception associated with adenovirus infection in Mexican children. Am J Clin Pathol. 2003;120(6):845–50.PubMedCrossRefGoogle Scholar
  115. 115.
    Ison MG. Adenovirus infections in transplant recipients. Clin Infect Dis. 2006;43(3):331–9.PubMedCrossRefGoogle Scholar
  116. 116.
    Muller WJ, Levin MJ, Shin YK, Robinson C, Quinones R, Malcolm J, et al. Clinical and in vitro evaluation of cidofovir for treatment of adenovirus infection in pediatric hematopoietic stem cell transplant recipients. Clin Infect Dis. 2005;41(12):1812–6.PubMedCrossRefGoogle Scholar
  117. 117.
    Funk GA, Gosert R, Hirsch HH. Viral dynamics in transplant patients: implications for disease. Lancet Infect Dis. 2007;7(7):460–72.PubMedCrossRefGoogle Scholar
  118. 118.
    Forstmeyer D, Henke-Gendo C, Brocker V, Wildner O, Heim A. Quantitative temporal and spatial distribution of adenovirus type 2 correlates with disease manifestations and organ failure during disseminated infection. J Med Virol. 2008;80(2):294–7.PubMedCrossRefGoogle Scholar
  119. 119.
    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(6):481–6.PubMedCrossRefGoogle Scholar
  120. 120.
    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(5):873–85.PubMedCrossRefGoogle Scholar
  121. 121.
    Ajuebor MN, Jin Y, Gremillion GL, Strieter RM, Chen Q, Adegboyega PA. GammadeltaT cells initiate acute inflammation and injury in adenovirus-infected liver via cytokine-chemokine cross talk. J Virol. 2008;82(19):9564–76.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Biron CA, Brossay L. NK cells and NKT cells in innate defense against viral infections. Curr Opin Immunol. 2001;13(4):458–64.PubMedCrossRefGoogle Scholar
  123. 123.
    Stone D, Liu Y, Shayakhmetov D, Li ZY, Ni S, Lieber A. Adenovirus-platelet interaction in blood causes virus sequestration to the reticuloendothelial system of the liver. J Virol. 2007;81(9):4866–71.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Holdener M, Hintermann E, Bayer M, Rhode A, Rodrigo E, Hintereder G, et al. Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection. J Exp Med. 2008;205(6):1409–22.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    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(12):1333–8.PubMedCrossRefGoogle Scholar
  126. 126.
    Shields AF, Hackman RC, Fife KH, Corey L, Meyers JD. Adenovirus infections in patients undergoing bone-marrow transplantation. N Engl J Med. 1985;312(9):529–33.PubMedCrossRefGoogle Scholar
  127. 127.
    Bil-Lula I, Ussowicz M, Rybka B, Wendycz-Domalewska D, Ryczan R, Gorczynska E, et al. Hematuria due to adenoviral infection in bone marrow transplant recipients. Transplant Proc. 2010;42(9):3729–34.PubMedCrossRefGoogle Scholar
  128. 128.
    Bateman CM, Kesson AM, Shaw PJ. Pancreatitis and adenoviral infection in children after blood and marrow transplantation. Bone Marrow Transplant. 2006;38(12):807–11.PubMedCrossRefGoogle Scholar
  129. 129.
    George D, El-Mallawany NK, Jin Z, Geyer M, Della-Latta P, Satwani P, et al. Adenovirus infection in paediatric allogeneic stem cell transplantation recipients is a major independent factor for significantly increasing the risk of treatment related mortality. Br J Haematol. 2012;156(1):99–108.PubMedCrossRefGoogle Scholar
  130. 130.
    Fejer G, Szalay K, Gyory I, Fejes M, Kusz E, Nedieanu S, et al. Adenovirus infection dramatically augments lipopolysaccharide-induced TNF production and sensitizes to lethal shock. J Immunol. 2005;175(3):1498–506.PubMedCrossRefGoogle Scholar
  131. 131.
    Mistchenko AS, Diez RA, Mariani AL, Robaldo J, Maffey AF, Bayley-Bustamante G, et al. Cytokines in adenoviral disease in children: association of interleukin-6, interleukin-8, and tumor necrosis factor alpha levels with clinical outcome. J Pediatr. 1994;124(5 Pt 1):714–20.PubMedCrossRefGoogle Scholar
  132. 132.
    Kampf G, Rudolf M, Labadie JC, Barrett SP. Spectrum of antimicrobial activity and user acceptability of the hand disinfectant agent Sterillium Gel. J Hosp Infect. 2002;52(2):141–7.PubMedCrossRefGoogle Scholar
  133. 133.
    Rutala WA, Peacock JE, Gergen MF, Sobsey MD, Weber DJ. Efficacy of hospital germicides against adenovirus 8, a common cause of epidemic keratoconjunctivitis in health care facilities. Antimicrob Agents Chemother. 2006;50(4):1419–24.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 134.
    Tablan OC, Anderson LJ, Besser R, Bridges C, Hajjeh R, Cdc, et al. Guidelines for preventing health-care—associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR Recommendations and reports: morbidity and mortality weekly report. Recommendations and reports/Centers for Disease Control. 2004;53(RR-3):1–36.Google Scholar
  135. 135.
    Raanani P, Gafter-Gvili A, Paul M, Ben-Bassat I, Leibovici L, Shpilberg O. Immunoglobulin prophylaxis in hematopoietic stem cell transplantation: systematic review and meta-analysis. J Clin Oncol. 2009;27(5):770–81.PubMedCrossRefGoogle Scholar
  136. 136.
    Morfin F, Dupuis-Girod S, Frobert E, Mundweiler S, Carrington D, Sedlacek P, et al. Differential susceptibility of adenovirus clinical isolates to cidofovir and ribavirin is not related to species alone. Antivir Ther. 2009;14(1):55–61.PubMedGoogle Scholar
  137. 137.
    Naesens L, Lenaerts L, Andrei G, Snoeck R, Van Beers D, Holy A, et al. Antiadenovirus activities of several classes of nucleoside and nucleotide analogues. Antimicrob Agents Chemother. 2005;49(3):1010–6.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    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(5):341–52.PubMedCrossRefGoogle Scholar
  139. 139.
    Gavin PJ, Katz BZ. Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children. Pediatrics. 2002;110(1 Pt 1):e9.PubMedCrossRefGoogle Scholar
  140. 140.
    Lankester AC, Heemskerk B, Claas EC, Schilham MW, Beersma MF, Bredius RG, et al. Effect of ribavirin on the plasma viral DNA load in patients with disseminating adenovirus infection. Clin Infect Dis. 2004;38(11):1521–5.PubMedCrossRefGoogle Scholar
  141. 141.
    Morfin F, Dupuis-Girod S, Mundweiler S, Falcon D, Carrington D, Sedlacek P, et al. In vitro susceptibility of adenovirus to antiviral drugs is species-dependent. Antivir Ther. 2005;10(2):225–9.PubMedGoogle Scholar
  142. 142.
    Lindemans CA, Leen AM, Boelens JJ. How I treat adenovirus in hematopoietic stem cell transplant recipients. Blood. 2010;116(25):5476–85.PubMedPubMedCentralCrossRefGoogle Scholar
  143. 143.
    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(7):388–94.PubMedCrossRefGoogle Scholar
  144. 144.
    Kim SJ, Kim K, Park SB, Hong DJ, Jhun BW. Outcomes of early administration of cidofovir in non-immunocompromised patients with severe adenovirus pneumonia. PLoS One. 2015;10(4):e0122642.PubMedPubMedCentralCrossRefGoogle Scholar
  145. 145.
    Lugthart G, Oomen MA, Jol-van der Zijde CM, Ball LM, Bresters D, Kollen WJ, et al. The effect of cidofovir on adenovirus plasma DNA levels in stem cell transplantation recipients without T cell reconstitution. Biol Blood Marrow Transplant. 2015;21(2):293–9.PubMedCrossRefGoogle Scholar
  146. 146.
    Lenaerts L, Kelchtermans H, Geboes L, Matthys P, Verbeken E, De Clercq E, et al. Recovery of humoral immunity is critical for successful antiviral therapy in disseminated mouse adenovirus type 1 infection. Antimicrob Agents Chemother. 2008;52(4):1462–71.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Painter W, Robertson A, Trost LC, Godkin S, Lampert B, Painter G. First pharmacokinetic and safety study in humans of the novel lipid antiviral conjugate CMX001, a broad-spectrum oral drug active against double-stranded DNA viruses. Antimicrob Agents Chemother. 2012;56(5):2726–34.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Toth K, Spencer JF, Dhar D, Sagartz JE, Buller RM, Painter GR, et al. Hexadecyloxypropyl-cidofovir, CMX001, prevents adenovirus-induced mortality in a permissive, immunosuppressed animal model. Proc Natl Acad Sci U S A. 2008;105(20):7293–7.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Florescu DF, Pergam SA, Neely MN, Qiu F, Johnston C, Way S, et al. Safety and efficacy of CMX001 as salvage therapy for severe adenovirus infections in immunocompromised patients. Biol Blood Marrow Transplant. 2012;18(5):731–8.PubMedCrossRefGoogle Scholar
  150. 150.
    Paolino K, Sande J, Perez E, Loechelt B, Jantausch B, Painter W, et al. Eradication of disseminated adenovirus infection in a pediatric hematopoietic stem cell transplantation recipient using the novel antiviral agent CMX001. J Clin Virol. 2011;50(2):167–70.PubMedCrossRefGoogle Scholar
  151. 151.
    Chatziandreou I, Gilmour KC, McNicol AM, Costabile M, Sinclair J, Cubitt D, et al. Capture and generation of adenovirus specific T cells for adoptive immunotherapy. Br J Haematol. 2007;136(1):117–26.PubMedCrossRefGoogle Scholar
  152. 152.
    Comoli P, Schilham MW, Basso S, van Vreeswijk T, Bernardo ME, Maccario R, et al. T-cell lines specific for peptides of adenovirus hexon protein and devoid of alloreactivity against recipient cells can be obtained from HLA-haploidentical donors. J Immunother. 2008;31(6):529–36.PubMedCrossRefGoogle Scholar
  153. 153.
    Feuchtinger T, Richard C, Joachim S, Scheible MH, Schumm M, Hamprecht K, et al. Clinical grade generation of hexon-specific T cells for adoptive T-cell transfer as a treatment of adenovirus infection after allogeneic stem cell transplantation. J Immunother. 2008;31(2):199–206.PubMedCrossRefGoogle Scholar
  154. 154.
    Regn S, Raffegerst S, Chen X, Schendel D, Kolb HJ, Roskrow M. 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(1):53–64.PubMedCrossRefGoogle Scholar
  155. 155.
    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(19):4283–92.PubMedPubMedCentralCrossRefGoogle Scholar
  156. 156.
    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(1):64–76.PubMedCrossRefGoogle Scholar
  157. 157.
    Amrolia PJ, Muccioli-Casadei G, Huls H, Adams S, Durett A, Gee A, et al. Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation. Blood. 2006;108(6):1797–808.PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Dorrie J, Krug C, Hofmann C, Muller I, Wellner V, Knippertz I, et al. Human adenovirus-specific gamma/delta and CD8+ T cells generated by T-cell receptor transfection to treat adenovirus infection after allogeneic stem cell transplantation. PLoS One. 2014;9(10):e109944.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    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(26):5113–23.PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143–238.PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    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(4):314–21.PubMedCrossRefGoogle Scholar
  162. 162.
    Legrand F, Berrebi D, Houhou N, Freymuth F, Faye A, Duval M, et al. Early diagnosis of adenovirus infection and treatment with cidofovir after bone marrow transplantation in children. Bone Marrow Transplant. 2001;27(6):621–6.PubMedCrossRefGoogle Scholar
  163. 163.
    Neofytos D, Ojha A, Mookerjee B, Wagner J, Filicko J, Ferber A, et al. Treatment of adenovirus disease in stem cell transplant recipients with cidofovir. Biol Blood Marrow Transplant. 2007;13(1):74–81.PubMedCrossRefGoogle Scholar
  164. 164.
    Verdeguer A, de Heredia CD, Gonzalez M, Martinez AM, Fernandez-Navarro JM, Perez-Hurtado JM, et al. Observational prospective study of viral infections in children undergoing allogeneic hematopoietic cell transplantation: a 3-year GETMON experience. Bone Marrow Transplant. 2011;46(1):119–24.PubMedCrossRefGoogle Scholar
  165. 165.
    Watson T, MacDonald D, Song X, Bromwich K, Campos J, Sande J, et al. Risk factors for molecular detection of adenovirus in pediatric hematopoietic stem cell transplantation recipients. Biol Blood Marrow Transplant. 2012;18(8):1227–34.PubMedCrossRefGoogle Scholar
  166. 166.
    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(10):1398–404.PubMedCrossRefGoogle Scholar
  167. 167.
    Di Nardo M, Li Pira G, Amodeo A, Cecchetti C, Giorda E, Ceccarelli S, et al. Adoptive immunotherapy with antigen-specific T cells during extracorporeal membrane oxygenation (ECMO) for adenovirus-related respiratory failure in a child given haploidentical stem cell transplantation. Pediatr Blood Cancer. 2014;61(2):376–9.PubMedCrossRefGoogle Scholar
  168. 168.
    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(12):1986–94.PubMedCrossRefGoogle Scholar
  169. 169.
    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(11):2113–21.PubMedPubMedCentralCrossRefGoogle Scholar
  170. 170.
    Qasim W, Gilmour K, Zhan H, Derniame S, McNicol AM, Ip W, et al. Interferon-gamma capture T cell therapy for persistent Adenoviraemia following allogeneic haematopoietic stem cell transplantation. Br J Haematol. 2013;161(3):449–52.PubMedCrossRefGoogle Scholar
  171. 171.
    Uhlin M, Gertow J, Uzunel M, Okas M, Berglund S, Watz E, et al. Rapid salvage treatment with virus-specific T cells for therapy-resistant disease. Clin Infect Dis. 2012;55(8):1064–73.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Open Access This chapter is distributed under the terms of the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Authors and Affiliations

  1. 1.Department of Stem Cell TransplantationSt. Anna Children’s Hospital, Medical UniversityViennaAustria

Personalised recommendations