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Management of CMV, HHV-6, HHV-7 and Kaposi-sarcoma herpesvirus (HHV-8) infections in patients with hematological malignancies and after SCT

Abstract

These recommendations were prepared by the European Conference on Infections in Leukaemia following a predefined methodology. Literature searches were made to identify studies pertinent to management of CMV, HHV-6, -7 and -8 infections. For CMV, 76 studies were reviewed: 72 published and 4 presented as abstracts. Twenty-nine of these studies were prospective randomized trials. For the other herpesviruses, HHV-6, -7 and -8, no randomized controlled trial has been performed, although data from some studies with other primary endpoints have been used to assess the management of HHV-6 infection. Works presented only as abstracts were used to a very limited extent. The quality of evidence and level of recommendation were graded according to the Center for Disease Control (CDC) criteria.

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References

  1. Cordonnier C, Calandra T . The first European conference on infections in leukaemia: why and how? Eur J Cancer Suppl 2007; 5: 2–4.

    Google Scholar 

  2. Boeckh M, Leisenring W, Riddell SR, Bowden RA, Huang ML, Myerson D et al. Late cytomegalovirus disease and mortality in recipients of allogeneic hematopoietic stem cell transplants: importance of viral load and T-cell immunity. Blood 2003; 101: 407–414.

    CAS  PubMed  Google Scholar 

  3. Krause H, Hebart H, Jahn G, Muller CA, Einsele H . Screening for CMV-specific T cell proliferation to identify patients at risk of developing late onset CMV disease. Bone Marrow Transplantation 1997; 19: 1111–1116.

    CAS  PubMed  Google Scholar 

  4. Zaia JA, Gallez-Hawkins GM, Tegtmeier BR, ter Veer A, Li X, Niland JC et al. Late cytomegalovirus disease in marrow transplantation is predicted by virus load in plasma. J Infect Dis 1997; 176: 782–785.

    CAS  PubMed  Google Scholar 

  5. Broers AE, van Der Holt R, van Esser JW, Gratama JW, Henzen-Logmans S, Kuenen-Boumeester V et al. Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplantation. Blood 2000; 95: 2240–2245.

    CAS  PubMed  Google Scholar 

  6. Craddock C, Szydlo RM, Dazzi F, Olavarria E, Cwynarski K, Yong A et al. Cytomegalovirus seropositivity adversely influences outcome after T-depleted unrelated donor transplant in patients with chronic myeloid leukaemia: the case for tailored graft-versus-host disease prophylaxis. Br J Haematol 2001; 112: 228–236.

    CAS  PubMed  Google Scholar 

  7. Meijer E, Dekker AW, Rozenberg-Arska M, Weersink AJ, Verdonck LF . Influence of cytomegalovirus seropositivity on outcome after T cell-depleted bone marrow transplantation: contrasting results between recipients of grafts from related and unrelated donors. Clin Infect Dis 2002; 35: 703–712.

    PubMed  Google Scholar 

  8. Boeckh M, Nichols WG . The impact of cytomegalovirus serostatus of donor and recipient before hematopoietic stem cell transplantation in the era of antiviral prophylaxis and preemptive therapy. Blood 2004; 103: 2003–2008.

    CAS  PubMed  Google Scholar 

  9. Mera JR, Whimbey E, Elting L, Preti A, Luna MA, Bruner JM et al. Cytomegalovirus pneumonia in adult nontransplantation patients with cancer: review of 20 cases occurring from 1964 through 1990. Clin Infect Dis 1996; 22: 1046–1050.

    CAS  PubMed  Google Scholar 

  10. Nguyen Q, Estey E, Raad I, Rolston K, Kantarjian H, Jacobson K et al. Cytomegalovirus pneumonia in adults with leukemia: an emerging problem. Clin Infect Dis 2001; 32: 539–545.

    CAS  PubMed  Google Scholar 

  11. Han XY . Epidemiologic analysis of reactivated cytomegalovirus antigenemia in patients with cancer. J Clin Microbiol 2007; 45: 1126–1132.

    PubMed  PubMed Central  Google Scholar 

  12. Ljungman P, Griffiths P, Paya C . Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis 2002; 34: 1094–1097.

    Article  PubMed  Google Scholar 

  13. Meyers JD, Ljungman P, Fisher LD . Cytomegalovirus excretion as a predictor of cytomegalovirus disease after marrow transplantation: importance of cytomegalovirus viremia. J Infect Dis 1990; 162: 373–380.

    CAS  PubMed  Google Scholar 

  14. Boeckh M, Boivin G . Quantitation of cytomegalovirus: methodologic aspects and clinical applications. Clin Microbiol Rev 1998; 11: 533–554.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Einsele H, Hebart H, Kauffmann-Schneider C, Sinzger C, Jahn G, Bader P et al. Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection. Bone Marrow Transplant 2000; 25: 757–763.

    CAS  PubMed  Google Scholar 

  16. Emery VC, Sabin CA, Cope AV, Gor D, Hassan-Walker AF, Griffiths PD . Application of viral-load kinetics to identify patients who develop cytomegalovirus disease after transplantation. Lancet 2000; 355: 2032–2036.

    CAS  PubMed  Google Scholar 

  17. Limaye AP, Huang ML, Leisenring W, Stensland L, Corey L, Boeckh M . Cytomegalovirus (CMV) DNA load in plasma for the diagnosis of CMV disease before engraftment in hematopoietic stem-cell transplant recipients. J Infect Dis 2001; 183: 377–382.

    CAS  PubMed  Google Scholar 

  18. Ljungman P, Perez-Bercoff L, Jonsson J, Avetisyan G, Sparrelid E, Aschan J et al. Risk factors for the development of cytomegalovirus disease after allogeneic stem cell transplantation. Haematologica 2006; 91: 78–83.

    PubMed  Google Scholar 

  19. Hebart H, Wuchter P, Loeffler J, Gscheidle B, Hamprecht K, Sinzger C et al. Evaluation of the Murex CMV DNA Hybrid Capture assay (version 2.0) for early diagnosis of cytomegalovirus infection in recipients of an allogeneic stem cell transplant. Bone Marrow Transplant 2001; 28: 213–218.

    CAS  PubMed  Google Scholar 

  20. Hebart H, Ljungman P, Klingebiel T, Loeffler J, Lewensohhn-Fuchs I, Barkholt L et al. Prospective comparison of PCR-based versus late mRNA-based preemptive antiviral therapy for HCMV infection in patients after allogeneic stem cell transplantation. Blood 2003; 102: 195a.

    Google Scholar 

  21. Gerna G, Lilleri D, Baldanti F, Torsellini M, Giorgiani G, Zecca M et al. Human cytomegalovirus immediate-early mRNAemia versus pp65 antigenemia for guiding pre-emptive therapy in children and young adults undergoing hematopoietic stem cell transplantation: a prospective, randomized, open-label trial. Blood 2003; 101: 5053–5060.

    PubMed  Google Scholar 

  22. Drew WL . Laboratory diagnosis of cytomegalovirus infection and disease in immunocompromised patients. Curr Opin Infect Dis 2007; 20: 408–411.

    CAS  PubMed  Google Scholar 

  23. Nichols WG, Price TH, Gooley T, Corey L, Boeckh M . Transfusion-transmitted cytomegalovirus infection after receipt of leukoreduced blood products. Blood 2003; 101: 4195–4200.

    CAS  PubMed  Google Scholar 

  24. Ljungman P, Larsson K, Kumlien G, Aschan J, Barkholt L, Gustafsson-Jernberg A et al. Leukocyte depleted, unscreened blood products give a low risk for CMV infection and disease in CMV seronegative allogeneic stem cell transplant recipients with seronegative stem cell donors. Scand J Infect Dis 2002; 34: 347–350.

    PubMed  Google Scholar 

  25. Bowden R, Cays M, Schoch G, Sayers M, Slichter S, Welk K et al. Comparison of filtered blood (FB) to seronegative blood products (SB) for prevention of cytomegalovirus (CMV) infection after marrow transplant. Blood 1995; 86: 3598–3603.

    CAS  PubMed  Google Scholar 

  26. Blajchman MA, Goldman M, Freedman JJ, Sher GD . Proceedings of a consensus conference: prevention of post-transfusion CMV in the era of universal leukoreduction. Transfus Med Rev 2001; 15: 1–20.

    CAS  PubMed  Google Scholar 

  27. Ratko TA, Cummings JP, Oberman HA, Crookston KP, DeChristopher PJ, Eastlund DT et al. Evidence-based recommendations for the use of WBC-reduced cellular blood components. Transfusion 2001; 41: 1310–1319.

    CAS  PubMed  Google Scholar 

  28. Ljungman P, Einsele H, Frassoni F, Niederwieser D, Cordonnier C . Donor CMV serological status influences the outcome of CMVseropositive recipients after unrelated donor stem cell transplantation; an EBMT Megafile analysis. Blood 2003; 102: 4255–4260.

    CAS  PubMed  Google Scholar 

  29. Ringden O, Schaffer M, Le Blanc K, Persson U, Hauzenberger D, Abedi MR et al. Which donor should be chosen for hematopoietic stem cell transplantation among unrelated HLA-A, -B, and -DRB1 genomically identical volunteers? Biol Blood Marrow Transplant 2004; 10: 128–134.

    PubMed  Google Scholar 

  30. Kollman C, Howe CW, Anasetti C, Antin JH, Davies SM, Filipovich AH et al. Donor characteristics as risk factors in recipients after transplantation of bone marrow from unrelated donors: the effect of donor age. Blood 2001; 98: 2043–2051.

    CAS  PubMed  Google Scholar 

  31. O’Brien SM, Keating MJ, Mocarski ES . Updated guidelines on the management of cytomegalovirus reactivation in patients with chronic lymphocytic leukemia treated with alemtuzumab. Clin Lymphoma Myeloma 2006; 7: 125–130.

    PubMed  Google Scholar 

  32. Cheung WW, Tse E, Leung AY, Yuen KY, Kwong YL . Regular virologic surveillance showed very frequent cytomegalovirus reactivation in patients treated with alemtuzumab. Am J Hematol 2007; 82: 108–111.

    CAS  PubMed  Google Scholar 

  33. Nabhan C, Patton D, Gordon LI, Riley MB, Kuzel T, Tallman MS et al. A pilot trial of rituximab and alemtuzumab combination therapy in patients with relapsed and/or refractory chronic lymphocytic leukemia (CLL). Leuk Lymphoma 2004; 45: 2269–2273.

    CAS  PubMed  Google Scholar 

  34. Rieger K, Von Grunhagen U, Fietz T, Thiel E, Knauf W . Efficacy and tolerability of alemtuzumab (CAMPATH-1H) in the salvage treatment of B-cell chronic lymphocytic leukemia—change of regimen needed? Leuk Lymphoma 2004; 45: 345–349.

    CAS  PubMed  Google Scholar 

  35. Lundin J, Kimby E, Bjorkholm M, Broliden PA, Celsing F, Hjalmar V et al. Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). Blood 2002; 100: 768–773.

    CAS  PubMed  Google Scholar 

  36. Boeckh M, Gooley TA, Reusser P, Buckner CD, Bowden RA . Failure of high-dose acyclovir to prevent cytomegalovirus disease after autologous marrow transplantation. J Infect Dis 1995; 172: 939–943.

    CAS  PubMed  Google Scholar 

  37. Reusser P, Fisher LD, Buckner CD, Thomas ED, Meyers JD . Cytomegalovirus infection after autologous bone marrow transplantation: occurrence of cytomegalovirus disease and effect on engraftment. Blood 1990; 75: 1888–1894.

    CAS  PubMed  Google Scholar 

  38. Holmberg LA, Boeckh M, Hooper H, Leisenring W, Rowley S, Heimfeld S et al. Increased incidence of cytomegalovirus disease after autologous CD34-selected peripheral blood stem cell transplantation (see comments). Blood 1999; 94: 4029–4035.

    CAS  PubMed  Google Scholar 

  39. Fries BC, Riddell SR, Kim HW, Corey L, Dahlgren C, Woolfrey A et al. Cytomegalovirus disease before hematopoietic cell transplantation as a risk for complications after transplantation. Biol Blood Marrow Transplant 2005; 11: 136–148.

    PubMed  Google Scholar 

  40. Emery VC . Viral dynamics during active cytomegalovirus infection and pathology. Intervirology 1999; 42: 405–411.

    CAS  PubMed  Google Scholar 

  41. Gerna G, Lilleri D, Zecca M, Alessandrino EP, Baldanti F, Revello MG et al. Rising antigenemia levels may be misleading in pre-emptive therapy of human cytomegalovirus infection in allogeneic hematopoietic stem cell transplant recipients. Haematologica 2005; 90: 526–533.

    PubMed  Google Scholar 

  42. Lengerke C, Ljubicic T, Meisner C, Loeffler J, Sinzger C, Einsele H et al. Evaluation of the COBAS Amplicor HCMV Monitor for early detection and monitoring of human cytomegalovirus infection after allogeneic stem cell transplantation. Bone Marrow Transplant 2006; 38: 53–60.

    CAS  PubMed  Google Scholar 

  43. Winston DJ, Baden LR, Gabriel DA, Emmanouilides C, Shaw LM, Lange WR et al. Pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir in allogeneic stem cell transplant patients with graft-versus-host disease of the gastrointestinal tract. Biol Blood Marrow Transplant 2006; 12: 635–640.

    CAS  PubMed  Google Scholar 

  44. Einsele H, Reusser P, Bornhauser M, Kalhs P, Ehninger G, Hebart H et al. Oral valganciclovir leads to higher exposure to ganciclovir than intravenous ganciclovir in patients following allogeneic stem cell transplantation. Blood 2006; 107: 3002–3008.

    CAS  PubMed  Google Scholar 

  45. Volin L, Barkholt L, Nihtinen A, Aschan J, Uotinen H, Hägglund H et al. An open-label randomised study of oral valganciclovir versus intravenous ganciclovir for pre-emptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Bone Marrow Transplantation 2008; 42 (Suppl 1): S47.

    Google Scholar 

  46. van der Heiden PL, Kalpoe JS, Barge RM, Willemze R, Kroes AC, Schippers EF . Oral valganciclovir as pre-emptive therapy has similar efficacy on cytomegalovirus DNA load reduction as intravenous ganciclovir in allogeneic stem cell transplantation recipients. Bone Marrow Transplant 2006; 37: 693–698.

    CAS  PubMed  Google Scholar 

  47. Ayala E, Greene J, Sandin R, Perkins J, Field T, Tate C et al. Valganciclovir is safe and effective as pre-emptive therapy for CMV infection in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2006; 37: 851–856.

    CAS  PubMed  Google Scholar 

  48. Busca A, de Fabritiis P, Ghisetti V, Allice T, Mirabile M, Gentile G et al. Oral valganciclovir as preemptive therapy for cytomegalovirus infection post allogeneic stem cell transplantation. Transpl Infect Dis 2007; 9: 102–107.

    CAS  PubMed  Google Scholar 

  49. Reusser P, Einsele H, Lee J, Volin L, Rovira M, Engelhard D et al. Randomized multicenter trial of foscarnet versus ganciclovir for preemptive therapy of cytomegalovirus infection after allogeneic stem cell transplantation. Blood 2002; 99: 1159–1164.

    CAS  PubMed  Google Scholar 

  50. Ljungman P, Deliliers GL, Platzbecker U, Matthes-Martin S, Bacigalupo A, Einsele H et al. Cidofovir for cytomegalovirus infection and disease in allogeneic stem cell transplant recipients. The Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Blood 2001; 97: 388–392.

    CAS  PubMed  Google Scholar 

  51. Platzbecker U, Bandt D, Thiede C, Helwig A, Freiberg-Richter J, Schuler U et al. Successful preemptive cidofovir treatment for CMV antigenemia after dose-reduced conditioning and allogeneic blood stem cell transplantation. Transplantation 2001; 71: 880–885.

    CAS  PubMed  Google Scholar 

  52. Cesaro S, Zhou X, Manzardo C, Buonfrate D, Cusinato R, Tridello G et al. Cidofovir for cytomegalovirus reactivation in pediatric patients after hematopoietic stem cell transplantation. J Clin Virol 2005; 34: 129–132.

    CAS  PubMed  Google Scholar 

  53. Bacigalupo A, Bregante S, Tedone E, Isaza A, Van Lint MT, Trespi G et al. Combined foscarnet-ganciclovir treatment for cytomegalovirus infections after allogeneic hemopoietic stem cell transplantation. Transplantation 1996; 62: 376–380.

    CAS  PubMed  Google Scholar 

  54. Mattes FM, Hainsworth EG, Geretti AM, Nebbia G, Prentice G, Potter M et al. A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients. J Infect Dis 2004; 189: 1355–1361.

    CAS  PubMed  Google Scholar 

  55. Kaptein SJ, Efferth T, Leis M, Rechter S, Auerochs S, Kalmer M et al. The anti-malaria drug artesunate inhibits replication of cytomegalovirus in vitro and in vivo. Antiviral Res 2006; 69: 60–69.

    CAS  PubMed  Google Scholar 

  56. Levi ME, Mandava N, Chan LK, Weinberg A, Olson JL . Treatment of multidrug-resistant cytomegalovirus retinitis with systemically administered leflunomide. Transpl Infect Dis 2006; 8: 38–43.

    CAS  PubMed  Google Scholar 

  57. Ehlert K, Groll AH, Kuehn J, Vormoor J . Treatment of refractory CMV-infection following hematopoietic stem cell transplantation with the combination of foscarnet and leflunomide. Klin Padiatr 2006; 218: 180–184.

    CAS  PubMed  Google Scholar 

  58. Avery RK, Bolwell BJ, Yen-Lieberman B, Lurain N, Waldman WJ, Longworth DL et al. Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection. Bone Marrow Transplant 2004; 34: 1071–1075.

    CAS  PubMed  Google Scholar 

  59. Battiwalla M, Paplham P, Almyroudis NG, McCarthy A, Abdelhalim A, Elefante A et al. Leflunomide failure to control recurrent cytomegalovirus infection in the setting of renal failure after allogeneic stem cell transplantation. Transpl Infect Dis 2007; 9: 28–32.

    CAS  PubMed  Google Scholar 

  60. Nichols WG, Corey L, Gooley T, Drew WL, Miner R, Huang M et al. Rising pp65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes. Blood 2001; 97: 867–874.

    CAS  PubMed  Google Scholar 

  61. Brugiatelli M, Bandini G, Barosi G, Lauria F, Liso V, Marchetti M et al. Management of chronic lymphocytic leukemia: practice guidelines from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation. Haematologica 2006; 91: 1662–1673.

    PubMed  Google Scholar 

  62. Laurenti L, Piccioni P, Cattani P, Cingolani A, Efremov D, Chiusolo P et al. Cytomegalovirus reactivation during alemtuzumab therapy for chronic lymphocytic leukemia: incidence and treatment with oral ganciclovir. Haematologica 2004; 89: 1248–1252.

    CAS  PubMed  Google Scholar 

  63. Nguyen DD, Cao TM, Dugan K, Starcher SA, Fechter RL, Coutre SE . Cytomegalovirus viremia during campath-1h therapy for relapsed and refractory chronic lymphocytic leukemia and prolymphocytic leukemia. Clin Lymphoma 2002; 3: 105–110.

    CAS  PubMed  Google Scholar 

  64. Keating M, Coutre S, Rai K, Osterborg A, Faderl S, Kennedy B et al. Management guidelines for use of alemtuzumab in B-cell chronic lymphocytic leukemia. Clin Lymphoma 2004; 4: 220–227.

    CAS  PubMed  Google Scholar 

  65. Visani G, Mele A, Guiducci B, D’Adamo F, Leopardi G, Barulli S et al. An observational study of once weekly intravenous ganciclovir as CMV prophylaxis in heavily pre-treated chronic lymphocytic leukemia patients receiving subcutaneous alemtuzumab. Leuk Lymphoma 2006; 47: 2542–2546.

    CAS  PubMed  Google Scholar 

  66. Oscier D, Fegan C, Hillmen P, Illidge T, Johnson S, Maguire P et al. Guidelines on the diagnosis and management of chronic lymphocytic leukaemia. Br J Haematol 2004; 125: 294–317.

    CAS  PubMed  Google Scholar 

  67. National Comprehensive Cancer Network. NCCN practice guidelines in Oncology. Non-Hodgkin's Lymphomas. http://www.nccn.org/professionals/physician_gls/PDF/nhlpdf 2007.

  68. Thursky KA, Worth LJ, Seymour JF, Miles Prince H, Slavin MA . Spectrum of infecction, risk and recommendations for prophylaxis and screening among patients with lymphoproliferative disorders treated with alemtuzumab. Br J Haematol 2006; 132: 3–12.

    PubMed  Google Scholar 

  69. Moreton P, Kennedy B, Lucas G, Leach M, Rassam SM, Haynes A et al. Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol 2005; 23: 2971–2979.

    CAS  PubMed  Google Scholar 

  70. Worth LJ, Thursky KA . Cytomegalovirus reactivation in patients with chronic lymphocytic leukemia treated with alemtuzumab: prophylaxis vs pre-emptive strategies for prevention. Leuk Lymphoma 2006; 47: 2435–2436.

    CAS  PubMed  Google Scholar 

  71. Singhal S, Powles R, Treleaven J, Horton C, Pinkerton CR, Meller S et al. Cytomegaloviremia after autografting for leukemia: clinical significance and lack of effect on engraftment. Leukemia 1997; 11: 835–838.

    CAS  PubMed  Google Scholar 

  72. Bilgrami S, Aslanzadeh J, Feingold JM, Bona RD, Clive J, Dorsky D et al. Cytomegalovirus viremia, viruria and disease after autologous peripheral blood stem cell transplantation: no need for surveillance. Bone Marrow Transplant 1999; 24: 69–73.

    CAS  PubMed  Google Scholar 

  73. Bowden RA, Fisher LD, Rogers K, Cays M, Meyers JD . Cytomegalovirus (CMV)-specific intravenous immunoglobulin for the prevention of primary CMV infection and disease after marrow transplant (see comments). J Infect Dis 1991; 164: 483–487.

    CAS  PubMed  Google Scholar 

  74. Prentice HG, Gluckman E, Powles RL, Ljungman P, Milpied N, Fernandez Ranada JM et al. Impact of long-term acyclovir on cytomegalovirus infection and survival after allogeneic bone marrow transplantation. European Acyclovir for CMV Prophylaxis Study Group. Lancet 1994; 343: 749–753.

    CAS  PubMed  Google Scholar 

  75. Ljungman P, De La Camara R, Milpied N, Volin L, Russell CA, Webster A et al. A randomised study of valaciclovir as prophylaxis against CMV reactivation in allogeneic bone marrow transplant recipients. Blood 2002; 73: 930–936.

    Google Scholar 

  76. Goodrich JM, Bowden RA, Fisher L, Keller C, Schoch G, Meyers JD . Ganciclovir prophylaxis to prevent cytomegalovirus disease after allogeneic marrow transplant. Ann Intern Med 1993; 118: 173–178.

    CAS  PubMed  Google Scholar 

  77. Winston DJ, Ho WG, Bartoni K, Du Mond C, Ebeling DF, Buhles WC et al. Ganciclovir prophylaxis of cytomegalovirus infection and disease in allogeneic bone marrow transplant recipients. Results of a placebo-controlled, double-blind trial. Ann Intern Med 1993; 118: 179–184.

    CAS  PubMed  Google Scholar 

  78. Boeckh M, Gooley TA, Myerson D, Cunningham T, Schoch G, Bowden RA . Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study. Blood 1996; 88: 4063–4071.

    CAS  PubMed  Google Scholar 

  79. Winston DJ, Yeager AM, Chandrasekar PH, Snydman DR, Petersen FB, Territo MC . Randomized comparison of oral valacyclovir and intravenous ganciclovir for prevention of cytomegalovirus disease after allogeneic bone marrow transplantation. Clin Infect Dis 2003; 36: 749–758.

    CAS  PubMed  Google Scholar 

  80. O’Brien S, Ravandi F, Riehl T, Wierda W, Huang X, Tarrand J et al. Valganciclovir prevents CMV reactivation in patients receiving alemtuzumab based therapy. Blood 2007; 111: 1816–1819.

    PubMed  Google Scholar 

  81. Machado CM, Dulley FL, Boas LS, Castelli JB, Macedo MC, Silva RL et al. CMV pneumonia in allogeneic BMT recipients undergoing early treatment of pre-emptive ganciclovir therapy. Bone Marrow Transplant 2000; 26: 413–417.

    CAS  PubMed  Google Scholar 

  82. Crippa F, Corey L, Chuang EL, Sale G, Boeckh M . Virological, clinical, and ophthalmologic features of cytomegalovirus retinitis after hematopoietic stem cell transplantation. Clin Infect Dis 2001; 32: 214–219.

    CAS  PubMed  Google Scholar 

  83. Larsson K, Lönnqvist B, Ringdén O, Hedquist B, Ljungman P . CMV retinitis after allogeneic bone marrow transplantation; a report of five cases. Transpl Infect Dis 2002; 4: 75–79.

    PubMed  Google Scholar 

  84. Emanuel D, Cunningham I, Jules EK, Brochstein JA, Kernan NA, Laver J et al. Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin. Ann Intern Med 1988; 109: 777–782.

    CAS  PubMed  Google Scholar 

  85. Ljungman P, Engelhard D, Link H, Biron P, Brandt L, Brunet S et al. Treatment of interstitial pneumonitis due to cytomegalovirus with ganciclovir and intravenous immune globulin: experience of European Bone Marrow Transplant Group. Clin Infect Dis 1992; 14: 831–835.

    CAS  PubMed  Google Scholar 

  86. Reed EC, Bowden RA, Dandliker PS, Lilleby KE, Meyers JD . Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants. Ann Intern Med 1988; 109: 783–788.

    CAS  PubMed  Google Scholar 

  87. Schmidt GM, Kovacs A, Zaia JA, Horak DA, Blume KG, Nademanee AP et al. Ganciclovir/immunoglobulin combination therapy for the treatment of human cytomegalovirus-associated interstitial pneumonia in bone marrow allograft recipients. Transplantation 1988; 46: 905–907.

    CAS  PubMed  Google Scholar 

  88. Erard V, Guthrie K, Smith J, Chien J, Corey L, Boeckh M . Cytomegalovirus pneumonia (CMV-IP) after hematopoietic cell transplantation (HCT): outcomes and factors associated with mortality. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Chicago 2007.

  89. Ljungman P, Cordonnier C, Einsele H, Bender-Gotze C, Bosi A, Dekker A et al. Use of intravenous immune globulin in addition to antiviral therapy in the treatment of CMV gastrointestinal disease in allogeneic bone marrow transplant patients: a report from the European Group for Blood and Marrow Transplantation (EBMT). Infectious Diseases Working Party of the EBMT. Bone Marrow Transplant 1998; 21: 473–476.

    CAS  PubMed  Google Scholar 

  90. Reed EC, Wolford JL, Kopecky KJ, Lilleby KE, Dandliker PS, Todaro JL et al. Ganciclovir for the treatment of cytomegalovirus gastroenteritis in bone marrow transplant patients. A randomized, placebo-controlled trial. Ann Intern Med 1990; 112: 505–510.

    CAS  PubMed  Google Scholar 

  91. Reusser P, Cordonnier C, Einsele H, Engelhard D, Link D, Locasciulli A et al. European survey of herpesvirus resistance to antiviral drugs in bone marrow transplant recipients. Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 1996; 17: 813–817.

    CAS  PubMed  Google Scholar 

  92. Hakki M, Riddell SR, Storek J, Carter RA, Stevens-Ayers T, Sudour P et al. Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation: impact of host factors, drug therapy, and subclinical reactivation. Blood 2003; 102: 3060–3067.

    CAS  PubMed  Google Scholar 

  93. Reusser P, Riddell SR, Meyers JD, Greenberg PD . Cytotoxic T-lymphocyte response to cytomegalovirus after human allogeneic bone marrow transplantation: pattern of recovery and correlation with cytomegalovirus infection and disease. Blood 1991; 78: 1373–1380.

    CAS  PubMed  Google Scholar 

  94. Ljungman P, Aschan J, Azinge JN, Brandt L, Ehrnst A, Hammarstrom V et al. Cytomegalovirus viraemia and specific T-helper cell responses as predictors of disease after allogeneic marrow transplantation. Br J Haematol 1993; 83: 118–124.

    CAS  PubMed  Google Scholar 

  95. Einsele H, Roosnek E, Rufer N, Sinzger C, Riegler S, Loffler J et al. Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood 2002; 99: 3916–3922.

    CAS  PubMed  Google Scholar 

  96. Walter EA, Greenberg PD, Gilbert MJ, Finch RJ, Watanabe KS, Thomas ED et al. Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med 1995; 333: 1038–1044.

    CAS  PubMed  Google Scholar 

  97. Szmania S, Galloway A, Bruorton M, Musk P, Aubert G, Arthur A et al. Isolation and expansion of cytomegalovirus-specific cytotoxic T lymphocytes to clinical scale from a single blood draw using dendritic cells and HLA-tetramers. Blood 2001; 98: 505–512.

    CAS  PubMed  Google Scholar 

  98. Grigoleit GU, Kapp M, Hebart H, Fick K, Beck R, Jahn G et al. Dendritic cell vaccination in allogeneic stem cell recipients: induction of human cytomegalovirus (HCMV)-specific cytotoxic T lymphocyte responses even in patients receiving a transplant from an HCMV-seronegative donor. J Infect Dis 2007; 196: 699–704.

    PubMed  Google Scholar 

  99. Yamanishi K, Okuno T, Shiraki K, Takahashi M, Kondo T, Asano Y et al. Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet 1988; I: 1065–1067.

    Google Scholar 

  100. Yoshikawa T, Asano Y, Ihira M, Suzuki K, Ohashi M, Suga S et al. Human herpesvirus 6 viremia in bone marrow transplant recipients: clinical features and risk factors. J Infect Dis 2002; 185: 847–853.

    PubMed  Google Scholar 

  101. Yoshikawa T, Suga S, Asano Y, Nakashima T, Yazaki T, Sobue R et al. Human herpesvirus-6 infection in bone marrow transplantation. Blood 1991; 78: 1381–1384.

    CAS  PubMed  Google Scholar 

  102. Reddy S, Manna P . Quantitative detection and differentiation of human herpesvirus 6 subtypes in bone marrow transplant patients by using a single real-time polymerase chain reaction assay. Biol Bone Marrow Transplant 2005; 11: 530–541.

    CAS  Google Scholar 

  103. Zerr DM, Corey L, Kim HW, Huang ML, Nguy L, Boeckh M . Clinical outcomes of human herpesvirus 6 reactivation after hematopoietic stem cell transplantation. Clin Infect Dis 2005; 40: 932–940.

    PubMed  Google Scholar 

  104. Wang FZ, Dahl H, Linde A, Brytting M, Ehrnst A, Ljungman P . Lymphotropic herpesviruses in allogeneic bone marrow transplantation. Blood 1996; 88: 3615–3620.

    CAS  PubMed  Google Scholar 

  105. Wang FZ, Linde A, Hagglund H, Testa M, Locasciulli A, Ljungman P . Human herpesvirus 6 DNA in cerebrospinal fluid specimens from allogeneic bone marrow transplant patients: does it have clinical significance? Clin Infect Dis 1999; 28: 562–568.

    CAS  PubMed  Google Scholar 

  106. Zerr DM, Gooley TA, Yeung L, Huang ML, Carpenter P, Wade JC et al. Human herpesvirus 6 reactivation and encephalitis in allogeneic bone marrow transplant recipients. Clin Infect Dis 2001; 33: 763–771.

    CAS  PubMed  Google Scholar 

  107. Isomura H, Yamada M, Yoshida M, Tanaka H, Kitamura T, Oda M et al. Suppressive effects of human herpesvirus 6 on in vitro colony formation of hematopoietic progenitor cells. J Med Virol 1997; 52: 406–412.

    CAS  PubMed  Google Scholar 

  108. Isomura H, Yoshida M, Namba H, Fujiwara N, Ohuchi R, Uno F et al. Suppressive effects of human herpesvirus-6 on thrombopoietin-inducible megakaryocytic colony formation in vitro. J Gen Virol 2000; 81 (Part 3): 663–673.

    CAS  PubMed  Google Scholar 

  109. Burd E, Knox K, Carrigan D . Human herpesvirus-6-associated suppression of growth factor-induced macrophage maturation in human bone marrow cultures. Blood 1993; 81: 1645–1650.

    CAS  PubMed  Google Scholar 

  110. Ljungman P, Wang FZ, Clark DA, Emery VC, Remberger M, Ringden O et al. High levels of human herpesvirus 6 DNA in peripheral blood leucocytes are correlated to platelet engraftment and disease in allogeneic stem cell transplant patients. Br J Haematol 2000; 111: 774–781.

    CAS  PubMed  Google Scholar 

  111. Boutolleau D, Fernandez C, Andre E, Imbert-Marcille BM, Milpied N, Agut H et al. Human herpesvirus (HHV)-6 and HHV-7: two closely related viruses with different infection profiles in stem cell transplantation recipients. J Infect Dis 2003; 187: 179–186.

    PubMed  Google Scholar 

  112. Luppi M, Marasca R, Barozzi P, Ferrari S, Ceccherini-Nelli L, Batoni G et al. Three cases of human herpesvirus-6 latent infection: integration of viral genome in peripheral blood mononuclear cell DNA. J Med Virol 1993; 40: 44–52.

    CAS  PubMed  Google Scholar 

  113. Torelli G, Barozzi P, Marasca R, Cocconcelli P, Merelli E, Ceccherini-Nelli L et al. Targeted integration of human herpesvirus 6 in the p arm of chromosome 17 of human peripheral blood mononuclear cells in vivo. J Med Virol 1995; 46: 178–188.

    CAS  PubMed  Google Scholar 

  114. Daibata M, Taguchi T, Nemoto Y, Taguchi H, Miyoshi I . Inheritance of chromosomally integrated human herpesvirus 6 DNA. Blood 1999; 94: 1545–1549.

    CAS  PubMed  Google Scholar 

  115. Tanaka-Taya K, Sashihara J, Kurahashi H, Amo K, Miyagawa H, Kondo K et al. Human herpesvirus 6 (HHV-6) is transmitted from parent to child in an integrated form and characterization of cases with chromosomally integrated HHV-6 DNA. J Med Virol 2004; 73: 465–473.

    PubMed  Google Scholar 

  116. Ward KN, Thiruchelvam AD, Couto-Parada X . Unexpected occasional persistence of high levels of HHV-6 DNA in sera; detection of variants A and B. J Med Virol 2005; 76: 563–570.

    CAS  PubMed  Google Scholar 

  117. Leong HN, Tuke PW, Tedder RS, Khalom AB, Eglin RP, Atkinson CE et al. The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors. J Med Virol 2007; 79: 45–51.

    CAS  PubMed  Google Scholar 

  118. Clark DA, Nacheva EP, Leong HN, Brazma D, Li YT, Tsao EH et al. Transmission of integrated human herpesvirus 6 through stem cell transplantation: implications for laboratory diagnosis. J Infect Dis 2006; 193: 912–916.

    PubMed  Google Scholar 

  119. Ward KN, Leong HN, Nacheva EP, Howard J, Atkinson CE, Davies NW et al. Human herpesvirus 6 chromosomal integration in immunocompetent patients results in high levels of viral DNA in blood, sera, and hair follicles. J Clin Microbiol 2006; 44: 1571–1574.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Ward KN, Leong HN, Thiruchelvam AD, Atkinson CE, Clark DA . HHV-6 DNA level in CSF due to primary infection differs from that in chromosomal viral Integration and has implications for the diagnosis of encephalitis. J Clin Microbiol 2007; 45: 1298–1304.

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Kamble RT, Clark DA, Leong HN, Heslop HE, Brenner MK, Carrum G . Transmission of integrated human herpesvirus-6 in allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 2007; 40: 563–566.

    CAS  PubMed  Google Scholar 

  122. Hubacek P, Maalouf J, Zajickova M, Kouba M, Cinek O, Hyncicova K et al. Failure of multiple antivirals to affect high HHV-6 DNAaemia resulting from viral chromosomal integration in a case of severe aplastic anaemia. Haematologica 2007; 92 (Online): e98–e100.

    CAS  PubMed  Google Scholar 

  123. Hubacek P, Hyncicova K, Muzikova K, Cinek O, Zajac M, Sedlacek P . Disappearance of pre-existing high HHV-6 DNA load in blood after allogeneic SCT. Bone Marrow Transplant 2007; 40: 805–806.

    CAS  PubMed  Google Scholar 

  124. Ward KN, Couto Parada X, Passas J, Thiruchelvam AD . Evaluation of specificity and sensitivity of indirect immunofluorescence tests for IgG to human herpesviruses-6 and-7. J Virol Methods 2002; 106: 107–113.

    CAS  PubMed  Google Scholar 

  125. Ward KN, Gray JJ, Joslin ME, Sheldon MJ . Avidity of IgG antibodies to human herpesvirus-6 distinguishes primary from recurrent infection in organ transplant recipients and excludes cross-reactivity with other herpesviruses. J Med Virol 1993; 39: 44–49.

    CAS  PubMed  Google Scholar 

  126. Lautenschlager I, Linnavuori K, Hockerstedt K . Human herpesvirus-6 antigenemia after liver transplantation. Transplantation 2000; 69: 2561–2566.

    CAS  PubMed  Google Scholar 

  127. Zerr DM . Human herpesvirus 6 and central nervous system disease in hematopoietic cell transplantation. J Clin Virol 2006; 37 (Suppl 1): S52–S56.

    CAS  PubMed  Google Scholar 

  128. Ljungman P, Singh N . Human herpesvirus-6 infection in solid organ and stem cell transplant recipients. J Clin Virol 2006; 37 (Suppl 1): S87–S91.

    CAS  PubMed  Google Scholar 

  129. Tokimasa S, Hara J, Osugi Y, Ohta H, Matsuda Y, Fujisaki H et al. Ganciclovir is effective for prophylaxis and treatment of human herpesvirus-6 in allogeneic stem cell transplantation. Bone Marrow Transplant 2002; 29: 595–598.

    CAS  PubMed  Google Scholar 

  130. Rapaport D, Engelhard D, Tagger G, Or R, Frenkel N . Antiviral prophylaxis may prevent human herpesvirus-6 reactivation in bone marrow transplant recipients. Transpl Infect Dis 2002; 4: 10–16.

    CAS  PubMed  Google Scholar 

  131. Zerr DM, Gupta D, Huang ML, Carter R, Corey L . Effect of antivirals on human herpesvirus 6 replication in hematopoietic stem cell transplant recipients. Clin Infect Dis 2002; 34: 309–317.

    CAS  PubMed  Google Scholar 

  132. Dewhurst S . Human herpesvirus type 6 and human herpesvirus type 7 infections of the central nervous system. Herpes 2004; 11 (Suppl 2): 105A–111A.

    PubMed  Google Scholar 

  133. Tanaka K, Kondo T, Torigoe S, Okada S, Mukai T, Yamanishi K . Human herpesvirus 7: another causal agent for roseola (exanthem subitum). J Pediatr 1994; 125: 1–5.

    CAS  PubMed  Google Scholar 

  134. Torigoe S, Kumamoto T, Koide W, Taya K, Yamanishi K . Clinical manifestations associated with human herpesvirus 7 infection. Arc Dis Child 1995; 72: 518–519.

    CAS  Google Scholar 

  135. Ward KN, Andrews NJ, Verity CM, Miller E, Ross EM . Human herpesviruses-6 and -7 each cause significant neurological morbidity in Britain and Ireland. Arch Dis Child 2005; 90: 619–623.

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Khanani M, Al Ahmari A, Tellier R, Allen U, Richardson S, Doyle JJ et al. Human herpesvirus 7 in pediatric hematopoietic stem cell transplantation. Pediatr Blood Cancer 2007; 48: 567–570.

    PubMed  Google Scholar 

  137. Chan PK, Chik KW, To KF, Li CK, Shing MM, Ng KC et al. Case report: human herpesvirus 7 associated fatal encephalitis in a peripheral blood stem cell transplant recipient. J Med Virol 2002; 66: 493–496.

    PubMed  Google Scholar 

  138. Chan PK, Peiris JS, Yuen KY, Liang RH, Lau YL, Chen FE et al. Human herpesvirus-6 and human herpesvirus-7 infections in bone marrow transplant recipients. J Med Virol 1997; 53: 295–305.

    CAS  PubMed  Google Scholar 

  139. Ward KN, White RP, Mackinnon S, Hanna M . Human herpesvirus-7 infection of the CNS with acute myelitis in an adult bone marrow recipient. Bone Marrow Transplant 2002; 30: 983–985.

    CAS  PubMed  Google Scholar 

  140. Yoshikawa T, Yoshida J, Hamaguchi M, Kubota T, Akimoto S, Ihira M et al. Human herpesvirus 7-associated meningitis and optic neuritis in a patient after allogeneic stem cell transplantation. J Med Virol 2003; 70: 440–443.

    PubMed  Google Scholar 

  141. Hladik W, Dollard SC, Mermin J, Fowlkes AL, Downing R, Amin MM et al. Transmission of human herpesvirus 8 by blood transfusion. N Engl J Med 2006; 355: 1331–1338.

    CAS  PubMed  Google Scholar 

  142. Regamey N, Tamm M, Wernli M, Witschi A, Thiel G, Cathomas G et al. Transmission of human herpesvirus 8 infection from renal-transplant donors to recipients. N Engl J Med 1998; 339: 1358–1363.

    CAS  PubMed  Google Scholar 

  143. Vivancos P, Sarra J, Palou J, Valls A, Garcia J, Granena A . Kaposi's sarcoma after autologous bone marrow transplantation for multiple myeloma. Bone Marrow Transplant 1996; 17: 669–671.

    CAS  PubMed  Google Scholar 

  144. Erer B, Angelucci E, Muretto P, Ripalti M, Rapa S, Gaziev D et al. Kaposi's sarcoma after allogeneic bone marrow transplantation. Bone Marrow Transplant 1997; 19: 629–631.

    CAS  PubMed  Google Scholar 

  145. Luppi M, Barozzi P, Schulz TF, Setti G, Staskus K, Trovato R et al. Bone marrow failure associated with human herpesvirus 8 infection after transplantation. N Engl J Med 2000; 343: 1378–1385.

    CAS  PubMed  Google Scholar 

  146. Luppi M, Barozzi P, Schulz TF, Trovato R, Donelli A, Narni F et al. Nonmalignant disease associated with human herpesvirus 8 reactivation in patients who have undergone autologous peripheral blood stem cell transplantation. Blood 2000; 96: 2355–2357.

    CAS  PubMed  Google Scholar 

  147. Cuzzola M, Irrera G, Iacopino O, Cuzzocrea A, Messina G, Console G et al. Bone marrow failure associated with herpesvirus 8 infection in a patient undergoing autologous peripheral blood stem cell transplantation. Clin Infect Dis 2003; 37: e102–e106.

    PubMed  Google Scholar 

  148. Sarmati L . Serological testing for human herpesvirus 8. Herpes 2001; 8: 76–79.

    CAS  PubMed  Google Scholar 

  149. CDC. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Recommendations of CDC, the Infectious Disease Society of America, and the American Society of Blood and Marrow Transplantation. MMWR Morb Mortal Wkly Rep 2000; 49 (RR-10): 1–125.

    Google Scholar 

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Ljungman, P., de la Camara, R., Cordonnier, C. et al. Management of CMV, HHV-6, HHV-7 and Kaposi-sarcoma herpesvirus (HHV-8) infections in patients with hematological malignancies and after SCT. Bone Marrow Transplant 42, 227–240 (2008). https://doi.org/10.1038/bmt.2008.162

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