Cytomegalovirus Infection After Stem Cell Transplantation

  • Morgan Hakki
  • Per Ljungman


Human cytomegalovirus (CMV) continues to be a cause of substantial morbidity and mortality in the hematopoietic cell transplant (HCT) recipient. Sensitive and rapid turnaround quantitative polymerase chain reaction (qPCR)-based monitoring coupled with the availability of effective antiviral therapy has reduced the overall burden of CMV disease after HCT. However, the increasing use of techniques such as cord blood and T-cell-depleted haploidentical transplant presents new challenges in the prevention and treatment of CMV. Gastrointestinal disease is now the most common end-organ manifestation of CMV infection after HCT, whereas pneumonia remains associated with high mortality. In addition, indirect effects of CMV infection continue to have both positive and negative effects on outcomes after HCT. Antivirals with novel mechanisms of action and improved toxicity profiles compared to those currently available are very much needed. The development of an effective vaccine has proven to be difficult. Therefore, CMV is likely to remain a significant pathogen in the HCT recipient in the years to come.


CMV Preemptive therapy Prophylaxis Pneumonia Retinitis Gastrointestinal disease 


  1. 1.
    Chee MS, Bankier AT, Beck S, Bohni R, Brown CM, Cerny R, et al. Analysis of the protein-coding content of the sequence of human cytomegalovirus strain AD169. Curr Top Microbiol Immunol. 1990;154:125–69.PubMedGoogle Scholar
  2. 2.
    Goodrum F, Caviness K, Zagallo P. Human cytomegalovirus persistence. Cell Microbiol. 2012;14(5):644–55.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Bolovan-Fritts CA, Mocarski ES, Wiedeman JA. Peripheral blood CD14(+) cells from healthy subjects carry a circular conformation of latent cytomegalovirus genome. Blood. 1999;93(1):394–8.PubMedGoogle Scholar
  4. 4.
    Slobedman B, Mocarski ES. Quantitative analysis of latent human cytomegalovirus. J Virol. 1999;73(6):4806–12.PubMedPubMedCentralGoogle Scholar
  5. 5.
    Soderberg-Naucler C, Fish KN, Nelson JA. Reactivation of latent human cytomegalovirus by allogeneic stimulation of blood cells from healthy donors. Cell. 1997;91(1):119–26.PubMedCrossRefGoogle Scholar
  6. 6.
    Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med. 2007;357(25):2601–14.PubMedCrossRefGoogle Scholar
  7. 7.
    Kern F, Bunde T, Faulhaber N, Kiecker F, Khatamzas E, Rudawski IM, et al. Cytomegalovirus (CMV) phosphoprotein 65 makes a large contribution to shaping the T cell repertoire in CMV-exposed individuals. J Infect Dis. 2002;185(12):1709–16.PubMedCrossRefGoogle Scholar
  8. 8.
    Kern F, Surel IP, Faulhaber N, Frommel C, Schneider-Mergener J, Schonemann C, et al. Target structures of the CD8(+)-T-cell response to human cytomegalovirus: the 72-kilodalton major immediate-early protein revisited. J Virol. 1999;73(10):8179–84.PubMedPubMedCentralGoogle Scholar
  9. 9.
    Khan N, Best D, Bruton R, Nayak L, Rickinson AB, Moss PA. T cell recognition patterns of immunodominant cytomegalovirus antigens in primary and persistent infection. J Immunol. 2007;178(7):4455–65.PubMedCrossRefGoogle Scholar
  10. 10.
    Khan N, Bruton R, Taylor GS, Cobbold M, Jones TR, Rickinson AB, et al. Identification of cytomegalovirus-specific cytotoxic T lymphocytes in vitro is greatly enhanced by the use of recombinant virus lacking the US2 to US11 region or modified vaccinia virus Ankara expressing individual viral genes. J Virol. 2005;79(5):2869–79.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Khan N, Cobbold M, Keenan R, Moss PA. Comparative analysis of CD8+ T cell responses against human cytomegalovirus proteins pp 65 and immediate early 1 shows similarities in precursor frequency, oligoclonality, and phenotype. J Infect Dis. 2002;185(8):1025–34.PubMedCrossRefGoogle Scholar
  12. 12.
    Kondo E, Akatsuka Y, Kuzushima K, Tsujimura K, Asakura S, Tajima K, et al. Identification of novel CTL epitopes of CMV-pp 65 presented by a variety of HLA alleles. Blood. 2004;103(2):630–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Elkington R, Walker S, Crough T, Menzies M, Tellam J, Bharadwaj M, et al. Ex vivo profiling of CD8+−T-cell responses to human cytomegalovirus reveals broad and multispecific reactivities in healthy virus carriers. J Virol. 2003;77(9):5226–40.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Sylwester AW, Mitchell BL, Edgar JB, Taormina C, Pelte C, Ruchti F, et al. Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med. 2005;202(5):673–85.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Manley TJ, Luy L, Jones T, Boeckh M, Mutimer H, Riddell SR. Immune evasion proteins of human cytomegalovirus do not prevent a diverse CD8+ cytotoxic T-cell response in natural infection. Blood. 2004;104(4):1075–82.PubMedCrossRefGoogle Scholar
  16. 16.
    Tey SK, Goodrum F, Khanna R. CD8+ T-cell recognition of human cytomegalovirus latency-associated determinant pUL138. J Gen Virol. 2010;91(Pt 8):2040–8.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    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(11):3916–22.PubMedCrossRefGoogle Scholar
  18. 18.
    Hebart H, Daginik S, Stevanovic S, Grigoleit U, Dobler A, Baur M, et al. Sensitive detection of human cytomegalovirus peptide-specific cytotoxic T-lymphocyte responses by interferon-gamma-enzyme-linked immunospot assay and flow cytometry in healthy individuals and in patients after allogeneic stem cell transplantation. Blood. 2002;99(10):3830–7.PubMedCrossRefGoogle Scholar
  19. 19.
    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 Transplant. 1997;19(11):1111–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Li CR, Greenberg PD, Gilbert MJ, Goodrich JM, Riddell SR. Recovery of HLA-restricted cytomegalovirus (CMV)-specific T-cell responses after allogeneic bone marrow transplant: correlation with CMV disease and effect of ganciclovir prophylaxis. Blood. 1994;83(7):1971–9.PubMedGoogle Scholar
  21. 21.
    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(1):118–24.PubMedCrossRefGoogle Scholar
  22. 22.
    Quinnan Jr GV, Kirmani N, Rook AH, Manischewitz JF, Jackson L, Moreschi G, et al. Cytotoxic t cells in cytomegalovirus infection: HLA-restricted T-lymphocyte and non-T-lymphocyte cytotoxic responses correlate with recovery from cytomegalovirus infection in bone-marrow-transplant recipients. N Engl J Med. 1982;307(1):7–13.PubMedCrossRefGoogle Scholar
  23. 23.
    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(5):1373–80.PubMedGoogle Scholar
  24. 24.
    Tormo N, Solano C, Benet I, Nieto J, de la Camara R, Lopez J, et al. Reconstitution of CMV pp 65 and IE-1-specific IFN-gamma CD8(+) and CD4(+) T-cell responses affording protection from CMV DNAemia following allogeneic hematopoietic SCT. Bone Marrow Transplant. 2011;46(11):1437–43.PubMedCrossRefGoogle Scholar
  25. 25.
    Widmann T, Sester U, Gartner BC, Schubert J, Pfreundschuh M, Kohler H, et al. Levels of CMV specific CD4 T cells are dynamic and correlate with CMV viremia after allogeneic stem cell transplantation. PLoS One. 2008;3(11), e3634.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Eid AJ, Brown RA, Hogan WJ, Lahr BD, Eckel-Passow JE, Litzow MR, et al. Kinetics of interferon-gamma producing cytomegalovirus (CMV)-specific CD4+ and CD8+ T lymphocytes and the risk of subsequent CMV viremia after allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis. 2009;11(6):519–28.PubMedCrossRefGoogle Scholar
  27. 27.
    Peccatori J, Forcina A, Clerici D, Crocchiolo R, Vago L, Stanghellini MT, et al. Sirolimus-based graft-versus-host disease prophylaxis promotes the in vivo expansion of regulatory T cells and permits peripheral blood stem cell transplantation from haploidentical donors. Leukemia. 2015;29(2):396–405.PubMedCrossRefGoogle Scholar
  28. 28.
    Brown JA, Stevenson K, Kim HT, Cutler C, Ballen K, McDonough S, et al. Clearance of CMV viremia and survival after double umbilical cord blood transplantation in adults depends on reconstitution of thymopoiesis. Blood. 2010;115(20):4111–9.PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    McGoldrick SM, Bleakley ME, Guerrero A, Turtle CJ, Yamamoto TN, Pereira SE, et al. Cytomegalovirus-specific T cells are primed early after cord blood transplant but fail to control virus in vivo. Blood. 2013;121(14):2796–803.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    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
  31. 31.
    Britt WJ, Vugler L, Butfiloski EJ, Stephens EB. Cell surface expression of human cytomegalovirus (HCMV) gp55-116 (gB): use of HCMV-recombinant vaccinia virus-infected cells in analysis of the human neutralizing antibody response. J Virol. 1990;64(3):1079–85.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Marshall GS, Rabalais GP, Stout GG, Waldeyer SL. Antibodies to recombinant-derived glycoprotein B after natural human cytomegalovirus infection correlate with neutralizing activity. J Infect Dis. 1992;165(2):381–4.PubMedCrossRefGoogle Scholar
  33. 33.
    Rasmussen L, Matkin C, Spaete R, Pachl C, Merigan TC. Antibody response to human cytomegalovirus glycoproteins gB and gH after natural infection in humans. J Infect Dis. 1991;164(5):835–42.PubMedCrossRefGoogle Scholar
  34. 34.
    Boppana SB, Britt WJ. Antiviral antibody responses and intrauterine transmission after primary maternal cytomegalovirus infection. J Infect Dis. 1995;171(5):1115–21.PubMedCrossRefGoogle Scholar
  35. 35.
    Jonjic S, Pavic I, Lucin P, Rukavina D, Koszinowski UH. Efficacious control of cytomegalovirus infection after long-term depletion of CD8+ T lymphocytes. J Virol. 1990;64(11):5457–64.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Jonjic S, Pavic I, Polic B, Crnkovic I, Lucin P, Koszinowski UH. Antibodies are not essential for the resolution of primary cytomegalovirus infection but limit dissemination of recurrent virus. J Exp Med. 1994;179(5):1713–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Paludan SR, Bowie AG, Horan KA, Fitzgerald KA. Recognition of herpesviruses by the innate immune system. Nat Rev Immunol. 2011;11(2):143–54.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Smith C, Khanna R. Immune regulation of human herpesviruses and its implications for human transplantation. Am J Transplant. 2013;13 Suppl 3:9–23. quiz.PubMedCrossRefGoogle Scholar
  39. 39.
    Boehme KW, Guerrero M, Compton T. Human cytomegalovirus envelope glycoproteins B and H are necessary for TLR2 activation in permissive cells. J Immunol. 2006;177(10):7094–102.PubMedCrossRefGoogle Scholar
  40. 40.
    Compton T, Kurt-Jones EA, Boehme KW, Belko J, Latz E, Golenbock DT, et al. Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2. J Virol. 2003;77(8):4588–96.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Juckem LK, Boehme KW, Feire AL, Compton T. Differential initiation of innate immune responses induced by human cytomegalovirus entry into fibroblast cells. J Immunol. 2008;180(7):4965–77.PubMedCrossRefGoogle Scholar
  42. 42.
    Delale T, Paquin A, Asselin-Paturel C, Dalod M, Brizard G, Bates EE, et al. MyD88-dependent and -independent murine cytomegalovirus sensing for IFN-alpha release and initiation of immune responses in vivo. J Immunol. 2005;175(10):6723–32.PubMedCrossRefGoogle Scholar
  43. 43.
    Tabeta K, Georgel P, Janssen E, Du X, Hoebe K, Crozat K, et al. Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection. Proc Natl Acad Sci U S A. 2004;101(10):3516–21.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    DeFilippis VR, Alvarado D, Sali T, Rothenburg S, Fruh K. Human cytomegalovirus induces the interferon response via the DNA sensor ZBP1. J Virol. 2010;84(1):585–98.PubMedCrossRefGoogle Scholar
  45. 45.
    DeFilippis VR, Sali T, Alvarado D, White L, Bresnahan W, Fruh KJ. Activation of the interferon response by human cytomegalovirus occurs via cytoplasmic double-stranded DNA but not glycoprotein B. J Virol. 2010;84(17):8913–25.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Krug A, French AR, Barchet W, Fischer JA, Dzionek A, Pingel JT, et al. TLR9-dependent recognition of MCMV by IPC and DC generates coordinated cytokine responses that activate antiviral NK cell function. Immunity. 2004;21(1):107–19.PubMedCrossRefGoogle Scholar
  47. 47.
    Varani S, Cederarv M, Feld S, Tammik C, Frascaroli G, Landini MP, et al. Human cytomegalovirus differentially controls B cell and T cell responses through effects on plasmacytoid dendritic cells. J Immunol. 2007;179(11):7767–76.PubMedCrossRefGoogle Scholar
  48. 48.
    Bravo D, Solano C, Gimenez E, Remigia MJ, Corrales I, Amat P, et al. Effect of the IL28B Rs12979860 C/T polymorphism on the incidence and features of active cytomegalovirus infection in allogeneic stem cell transplant patients. J Med Virol. 2014;86(5):838–44.PubMedCrossRefGoogle Scholar
  49. 49.
    Corrales I, Gimenez E, Solano C, Amat P, de la Camara R, Nieto J, et al. Incidence and dynamics of active cytomegalovirus infection in allogeneic stem cell transplant patients according to single nucleotide polymorphisms in donor and recipient CCR5, MCP-1, IL-10, and TLR9 genes. J Med Virol. 2015;87(2):248–55.PubMedCrossRefGoogle Scholar
  50. 50.
    Loeffler J, Steffens M, Arlt EM, Toliat MR, Mezger M, Suk A, et al. Polymorphisms in the genes encoding chemokine receptor 5, interleukin-10, and monocyte chemoattractant protein 1 contribute to cytomegalovirus reactivation and disease after allogeneic stem cell transplantation. J Clin Microbiol. 2006;44(5):1847–50.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Mezger M, Steffens M, Semmler C, Arlt EM, Zimmer M, Kristjanson GI, et al. Investigation of promoter variations in dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN) (CD209) and their relevance for human cytomegalovirus reactivation and disease after allogeneic stem-cell transplantation. Clin Microbiol Infect. 2008;14(3):228–34.PubMedCrossRefGoogle Scholar
  52. 52.
    Xiao HW, Luo Y, Lai XY, Shi JM, Tan YM, He JS, et al. Donor TLR9 gene tagSNPs influence susceptibility to aGVHD and CMV reactivation in the allo-HSCT setting without polymorphisms in the TLR4 and NOD2 genes. Bone Marrow Transplant. 2014;49(2):241–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Della Chiesa M, Falco M, Podesta M, Locatelli F, Moretta L, Frassoni F, et al. Phenotypic and functional heterogeneity of human NK cells developing after umbilical cord blood transplantation: a role for human cytomegalovirus? Blood. 2012;119(2):399–410.PubMedCrossRefGoogle Scholar
  54. 54.
    Guma M, Angulo A, Vilches C, Gomez-Lozano N, Malats N, Lopez-Botet M. Imprint of human cytomegalovirus infection on the NK cell receptor repertoire. Blood. 2004;104(12):3664–71.PubMedCrossRefGoogle Scholar
  55. 55.
    Guma M, Budt M, Saez A, Brckalo T, Hengel H, Angulo A, et al. Expansion of CD94/NKG2C+ NK cells in response to human cytomegalovirus-infected fibroblasts. Blood. 2006;107(9):3624–31.PubMedCrossRefGoogle Scholar
  56. 56.
    Malmberg KJ, Beziat V, Ljunggren HG. Spotlight on NKG2C and the human NK-cell response to CMV infection. Eur J Immunol. 2012;42(12):3141–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Muntasell A, Vilches C, Angulo A, Lopez-Botet M. Adaptive reconfiguration of the human NK-cell compartment in response to cytomegalovirus: a different perspective of the host-pathogen interaction. Eur J Immunol. 2013;43(5):1133–41.PubMedCrossRefGoogle Scholar
  58. 58.
    Della Chiesa M, Falco M, Bertaina A, Muccio L, Alicata C, Frassoni F, et al. Human cytomegalovirus infection promotes rapid maturation of NK cells expressing activating killer Ig-like receptor in patients transplanted with NKG2C−/− umbilical cord blood. J Immunol. 2014;192(4):1471–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Bukowski JF, Warner JF, Dennert G, Welsh RM. Adoptive transfer studies demonstrating the antiviral effect of natural killer cells in vivo. J Exp Med. 1985;161(1):40–52.PubMedCrossRefGoogle Scholar
  60. 60.
    Bukowski JF, Woda BA, Habu S, Okumura K, Welsh RM. Natural killer cell depletion enhances virus synthesis and virus-induced hepatitis in vivo. J Immunol. 1983;131(3):1531–8.PubMedGoogle Scholar
  61. 61.
    Polic B, Hengel H, Krmpotic A, Trgovcich J, Pavic I, Luccaronin P, et al. Hierarchical and redundant lymphocyte subset control precludes cytomegalovirus replication during latent infection. J Exp Med. 1998;188(6):1047–54.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Scalzo AA, Fitzgerald NA, Simmons A, La Vista AB, Shellam GR. Cmv-1, a genetic locus that controls murine cytomegalovirus replication in the spleen. J Exp Med. 1990;171(5):1469–83.PubMedCrossRefGoogle Scholar
  63. 63.
    Scalzo AA, Fitzgerald NA, Wallace CR, Gibbons AE, Smart YC, Burton RC, et al. The effect of the Cmv-1 resistance gene, which is linked to the natural killer cell gene complex, is mediated by natural killer cells. J Immunol. 1992;149(2):581–9.PubMedGoogle Scholar
  64. 64.
    Kuijpers TW, Baars PA, Dantin C, van den Burg M, van Lier RA, Roosnek E. Human NK cells can control CMV infection in the absence of T cells. Blood. 2008;112(3):914–5.PubMedCrossRefGoogle Scholar
  65. 65.
    Biron CA, Byron KS, Sullivan JL. Severe herpesvirus infections in an adolescent without natural killer cells. N Engl J Med. 1989;320(26):1731–5.PubMedCrossRefGoogle Scholar
  66. 66.
    Chen C, Busson M, Rocha V, Appert ML, Lepage V, Dulphy N, et al. Activating KIR genes are associated with CMV reactivation and survival after non-T-cell depleted HLA-identical sibling bone marrow transplantation for malignant disorders. Bone Marrow Transplant. 2006;38(6):437–44.PubMedCrossRefGoogle Scholar
  67. 67.
    Cook M, Briggs D, Craddock C, Mahendra P, Milligan D, Fegan C, et al. Donor KIR genotype has a major influence on the rate of cytomegalovirus reactivation following T-cell replete stem cell transplantation. Blood. 2006;107(3):1230–2.PubMedCrossRefGoogle Scholar
  68. 68.
    Zaia JA, Sun JY, Gallez-Hawkins GM, Thao L, Oki A, Lacey SF, et al. The effect of single and combined activating killer immunoglobulin-like receptor genotypes on cytomegalovirus infection and immunity after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2009;15(3):315–25.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Crough T, Khanna R. Immunobiology of human cytomegalovirus: from bench to bedside. Clin Microbiol Rev. 2009;22(1):76–98.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Sell S, Dietz M, Schneider A, Holtappels R, Mach M, Winkler TH. Control of murine cytomegalovirus infection by gammadelta T cells. PLoS Pathog. 2015;11(2), e1004481.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Turchinovich G, Pennington DJ. T cell receptor signalling in gammadelta cell development: strength isn’t everything. Trends Immunol. 2011;32(12):567–73.PubMedCrossRefGoogle Scholar
  72. 72.
    Lafarge X, Merville P, Cazin MC, Berge F, Potaux L, Moreau JF, et al. Cytomegalovirus infection in transplant recipients resolves when circulating gammadelta T lymphocytes expand, suggesting a protective antiviral role. J Infect Dis. 2001;184(5):533–41.PubMedCrossRefGoogle Scholar
  73. 73.
    Ninomiya T, Takimoto H, Matsuzaki G, Hamano S, Yoshida H, Yoshikai Y, et al. Vgamma1+ gammadelta T cells play protective roles at an early phase of murine cytomegalovirus infection through production of interferon-gamma. Immunology. 2000;99(2):187–94.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Pitard V, Roumanes D, Lafarge X, Couzi L, Garrigue I, Lafon ME, et al. Long-term expansion of effector/memory Vdelta2-gammadelta T cells is a specific blood signature of CMV infection. Blood. 2008;112(4):1317–24.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Abate DA, Watanabe S, Mocarski ES. Major human cytomegalovirus structural protein pp 65 (ppUL83) prevents interferon response factor 3 activation in the interferon response. J Virol. 2004;78(20):10995–1006.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Child SJ, Hakki M, De Niro KL, Geballe AP. Evasion of cellular antiviral responses by human cytomegalovirus TRS1 and IRS1. J Virol. 2004;78(1):197–205.PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Taylor RT, Bresnahan WA. Human cytomegalovirus immediate-early 2 gene expression blocks virus-induced beta interferon production. J Virol. 2005;79(6):3873–7.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Taylor RT, Bresnahan WA. Human cytomegalovirus immediate-early 2 protein IE86 blocks virus-induced chemokine expression. J Virol. 2006;80(2):920–8.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Goldmacher VS, Bartle LM, Skaletskaya A, Dionne CA, Kedersha NL, Vater CA, et al. A cytomegalovirus-encoded mitochondria-localized inhibitor of apoptosis structurally unrelated to Bcl-2. Proc Natl Acad Sci U S A. 1999;96(22):12536–41.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Nachmani D, Lankry D, Wolf DG, Mandelboim O. The human cytomegalovirus microRNA miR-UL112 acts synergistically with a cellular microRNA to escape immune elimination. Nat Immunol. 2010;11(9):806–13.PubMedCrossRefGoogle Scholar
  81. 81.
    Stern-Ginossar N, Elefant N, Zimmermann A, Wolf DG, Saleh N, Biton M, et al. Host immune system gene targeting by a viral miRNA. Science. 2007;317(5836):376–81.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Wilkinson GW, Tomasec P, Stanton RJ, Armstrong M, Prod’homme V, Aicheler R, et al. Modulation of natural killer cells by human cytomegalovirus. J Clin Virol. 2008;41(3):206–12.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Basta S, Bennink JR. A survival game of hide and seek: cytomegaloviruses and MHC class I antigen presentation pathways. Viral Immunol. 2003;16(3):231–42.PubMedCrossRefGoogle Scholar
  84. 84.
    Ahn K, Gruhler A, Galocha B, Jones TR, Wiertz EJ, Ploegh HL, et al. The ER-luminal domain of the HCMV glycoprotein US6 inhibits peptide translocation by TAP. Immunity. 1997;6(5):613–21.PubMedCrossRefGoogle Scholar
  85. 85.
    Furman MH, Dey N, Tortorella D, Ploegh HL. The human cytomegalovirus US10 gene product delays trafficking of major histocompatibility complex class I molecules. J Virol. 2002;76(22):11753–6.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Gilbert MJ, Riddell SR, Plachter B, Greenberg PD. Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product. Nature. 1996;383(6602):720–2.PubMedCrossRefGoogle Scholar
  87. 87.
    Jones TR, Sun L. Human cytomegalovirus US2 destabilizes major histocompatibility complex class I heavy chains. J Virol. 1997;71(4):2970–9.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Jones TR, Wiertz EJ, Sun L, Fish KN, Nelson JA, Ploegh HL. Human cytomegalovirus US3 impairs transport and maturation of major histocompatibility complex class I heavy chains. Proc Natl Acad Sci U S A. 1996;93(21):11327–33.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Miller DM, Rahill BM, Boss JM, Lairmore MD, Durbin JE, Waldman JW, et al. Human cytomegalovirus inhibits major histocompatibility complex class II expression by disruption of the Jak/Stat pathway. J Exp Med. 1998;187(5):675–83.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Miller DM, Zhang Y, Rahill BM, Waldman WJ, Sedmak DD. Human cytomegalovirus inhibits IFN-alpha-stimulated antiviral and immunoregulatory responses by blocking multiple levels of IFN-alpha signal transduction. J Immunol. 1999;162(10):6107–13.PubMedGoogle Scholar
  91. 91.
    Tomazin R, Boname J, Hegde NR, Lewinsohn DM, Altschuler Y, Jones TR, et al. Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4+ T cells. Nat Med. 1999;5(9):1039–43.PubMedCrossRefGoogle Scholar
  92. 92.
    Wiertz EJ, Jones TR, Sun L, Bogyo M, Geuze HJ, Ploegh HL. The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol. Cell. 1996;84(5):769–79.PubMedCrossRefGoogle Scholar
  93. 93.
    Benedict CA, Butrovich KD, Lurain NS, Corbeil J, Rooney I, Schneider P, et al. Cutting edge: a novel viral TNF receptor superfamily member in virulent strains of human cytomegalovirus. J Immunol. 1999;162(12):6967–70.PubMedGoogle Scholar
  94. 94.
    Chapman TL, Heikeman AP, Bjorkman PJ. The inhibitory receptor LIR-1 uses a common binding interaction to recognize class I MHC molecules and the viral homolog UL18. Immunity. 1999;11(5):603–13.PubMedCrossRefGoogle Scholar
  95. 95.
    Gao JL, Murphy PM. Human cytomegalovirus open reading frame US28 encodes a functional beta chemokine receptor. J Biol Chem. 1994;269(46):28539–42.PubMedGoogle Scholar
  96. 96.
    Kotenko SV, Saccani S, Izotova LS, Mirochnitchenko OV, Pestka S. Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10). Proc Natl Acad Sci U S A. 2000;97(4):1695–700.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Penfold ME, Dairaghi DJ, Duke GM, Saederup N, Mocarski ES, Kemble GW, et al. Cytomegalovirus encodes a potent alpha chemokine. Proc Natl Acad Sci U S A. 1999;96(17):9839–44.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Boeckh M, Boivin G. Quantitation of cytomegalovirus: methodologic aspects and clinical applications. Clin Microbiol Rev. 1998;11(3):533–54.PubMedPubMedCentralGoogle Scholar
  99. 99.
    Einsele H, Ehninger G, Hebart H, Wittkowski KM, Schuler U, Jahn G, et al. Polymerase chain reaction monitoring reduces the incidence of cytomegalovirus disease and the duration and side effects of antiviral therapy after bone marrow transplantation. Blood. 1995;86(7):2815–20.PubMedGoogle Scholar
  100. 100.
    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(2):373–80.PubMedCrossRefGoogle Scholar
  101. 101.
    Crawford SW, Bowden RA, Hackman RC, Gleaves CA, Meyers JD, Clark JG. Rapid detection of cytomegalovirus pulmonary infection by bronchoalveolar lavage and centrifugation culture. Ann Intern Med. 1988;108(2):180–5.PubMedCrossRefGoogle Scholar
  102. 102.
    Boeckh M, Bowden RA, Goodrich JM, Pettinger M, Meyers JD. Cytomegalovirus antigen detection in peripheral blood leukocytes after allogeneic marrow transplantation. Blood. 1992;80(5):1358–64.PubMedGoogle Scholar
  103. 103.
    Nichols WG, Corey L, Gooley T, Drew WL, Miner R, Huang M, et al. Rising pp 65 antigenemia during preemptive anticytomegalovirus therapy after allogeneic hematopoietic stem cell transplantation: risk factors, correlation with DNA load, and outcomes. Blood. 2001;97(4):867–74.PubMedCrossRefGoogle Scholar
  104. 104.
    Green ML, Leisenring W, Stachel D, Pergam SA, Sandmaier BM, Wald A, et al. Efficacy of a viral load-based, risk-adapted, preemptive treatment strategy for prevention of cytomegalovirus disease after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012;18(11):1687–99.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Jang EY, Park SY, Lee EJ, Song EH, Chong YP, Lee SO, et al. Diagnostic performance of the cytomegalovirus (CMV) antigenemia assay in patients with CMV gastrointestinal disease. Clin Infect Dis. 2009;48(12):e121–4.PubMedCrossRefGoogle Scholar
  106. 106.
    Mori T, Mori S, Kanda Y, Yakushiji K, Mineishi S, Takaue Y, et al. Clinical significance of cytomegalovirus (CMV) antigenemia in the prediction and diagnosis of CMV gastrointestinal disease after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2004;33(4):431–4.PubMedCrossRefGoogle Scholar
  107. 107.
    Ruell J, Barnes C, Mutton K, Foulkes B, Chang J, Cavet J, et al. Active CMV disease does not always correlate with viral load detection. Bone Marrow Transplant. 2007;40(1):55–61.PubMedCrossRefGoogle Scholar
  108. 108.
    Boeckh M, Huang M, Ferrenberg J, Stevens-Ayers T, Stensland L, Nichols WG, et al. Optimization of quantitative detection of cytomegalovirus DNA in plasma by real-time PCR. J Clin Microbiol. 2004;42(3):1142–8.PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    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(2):407–14.PubMedCrossRefGoogle Scholar
  110. 110.
    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(7):757–63.PubMedCrossRefGoogle Scholar
  111. 111.
    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(9220):2032–6.PubMedCrossRefGoogle Scholar
  112. 112.
    Gor D, Sabin C, Prentice HG, Vyas N, Man S, Griffiths PD, et al. Longitudinal fluctuations in cytomegalovirus load in bone marrow transplant patients: relationship between peak virus load, donor/recipient serostatus, acute GVHD and CMV disease. Bone Marrow Transplant. 1998;21(6):597–605.PubMedCrossRefGoogle Scholar
  113. 113.
    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(1):78–83.PubMedGoogle Scholar
  114. 114.
    Lisboa LF, Asberg A, Kumar D, Pang X, Hartmann A, Preiksaitis JK, et al. The clinical utility of whole blood versus plasma cytomegalovirus viral load assays for monitoring therapeutic response. Transplantation. 2011;91(2):231–6.PubMedCrossRefGoogle Scholar
  115. 115.
    Cathomas G, Morris P, Pekle K, Cunningham I, Emanuel D. Rapid diagnosis of cytomegalovirus pneumonia in marrow transplant recipients by bronchoalveolar lavage using the polymerase chain reaction, virus culture, and the direct immunostaining of alveolar cells. Blood. 1993;81(7):1909–14.PubMedGoogle Scholar
  116. 116.
    Gerna G, Lilleri D, Baldanti F, Torsellini M, Giorgiani G, Zecca M, et al. Human cytomegalovirus immediate-early mRNAemia versus pp 65 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(12):5053–60.PubMedCrossRefGoogle Scholar
  117. 117.
    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(11):195a.Google Scholar
  118. 118.
    Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002;34(8):1094–7.PubMedCrossRefGoogle Scholar
  119. 119.
    Boeckh M, Ljungman P. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood. 2009;113(23):5711–9.PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Kotloff RM, Ahya VN, Crawford SW. Pulmonary complications of solid organ and hematopoietic stem cell transplantation. Am J Respir Crit Care Med. 2004;170(1):22–48.PubMedCrossRefGoogle Scholar
  121. 121.
    Travi G, Pergam SA. Cytomegalovirus pneumonia in hematopoietic stem cell recipients. J Intensive Care Med. 2013;29(4):200–12.PubMedPubMedCentralCrossRefGoogle Scholar
  122. 122.
    Ariza-Heredia EJ, Nesher L, Chemaly RF. Cytomegalovirus diseases after hematopoietic stem cell transplantation: a mini-review. Cancer Lett. 2014;342(1):1–8.PubMedCrossRefGoogle Scholar
  123. 123.
    Franquet T, Lee KS, Muller NL. Thin-section CT findings in 32 immunocompromised patients with cytomegalovirus pneumonia who do not have AIDS. AJR Am J Roentgenol. 2003;181(4):1059–63.PubMedCrossRefGoogle Scholar
  124. 124.
    Gasparetto EL, Ono SE, Escuissato D, Marchiori E, Roldan L, Marques HL, et al. Cytomegalovirus pneumonia after bone marrow transplantation: high resolution CT findings. Br J Radiol. 2004;77(921):724–7.PubMedCrossRefGoogle Scholar
  125. 125.
    Schmidt GM, Horak DA, Niland JC, Duncan SR, Forman SJ, Zaia JA. A randomized, controlled trial of prophylactic ganciclovir for cytomegalovirus pulmonary infection in recipients of allogeneic bone marrow transplants; The City of Hope-Stanford-Syntex CMV Study Group. N Engl J Med. 1991;324(15):1005–11.PubMedCrossRefGoogle Scholar
  126. 126.
    Ljungman P. Cytomegalovirus pneumonia: presentation, diagnosis, and treatment. Semin Respir Infect. 1995;10(4):209–15.PubMedGoogle Scholar
  127. 127.
    Boeckh M, Gooley TA, Myerson D, Cunningham T, Schoch G, Bowden RA. Cytomegalovirus pp 65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study. Blood. 1996;88(10):4063–71.PubMedGoogle Scholar
  128. 128.
    Konoplev S, Champlin RE, Giralt S, Ueno NT, Khouri I, Raad I, et al. Cytomegalovirus pneumonia in adult autologous blood and marrow transplant recipients. Bone Marrow Transplant. 2001;27(8):877–81.PubMedCrossRefGoogle Scholar
  129. 129.
    Horger MS, Pfannenberg C, Einsele H, Beck R, Hebart H, Lengerke C, et al. Cytomegalovirus pneumonia after stem cell transplantation: correlation of CT findings with clinical outcome in 30 patients. AJR Am J Roentgenol. 2006;187(6):W636–43.PubMedCrossRefGoogle Scholar
  130. 130.
    Vigil KJ, Adachi JA, Chemaly RF. Viral pneumonias in immunocompromised adult hosts. J Intensive Care Med. 2010;25(6):307–26.PubMedCrossRefGoogle Scholar
  131. 131.
    Erard V, Guthrie KA, Seo S, Smith J, Huang M, Chien J, et al. Reduced mortality of cytomegalovirus pneumonia after hematopoietic cell transplantation due to antiviral therapy and changes in transplantation practices. Clin Infect Dis. 2015;61(1):31–9.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 132.
    van Burik JA, Lawatsch EJ, DeFor TE, Weisdorf DJ. Cytomegalovirus enteritis among hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant. 2001;7(12):674–9.PubMedCrossRefGoogle Scholar
  133. 133.
    Mori T, Okamoto S, Matsuoka S, Yajima T, Wakui M, Watanabe R, et al. Risk-adapted pre-emptive therapy for cytomegalovirus disease in patients undergoing allogeneic bone marrow transplantation. Bone Marrow Transplant. 2000;25(7):765–9.PubMedCrossRefGoogle Scholar
  134. 134.
    Coskuncan NM, Jabs DA, Dunn JP, Haller JA, Green WR, Vogelsang GB, et al. The eye in bone marrow transplantation. VI. Retinal complications. Arch Ophthalmol. 1994;112(3):372–9.PubMedCrossRefGoogle Scholar
  135. 135.
    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(2):214–9.PubMedCrossRefGoogle Scholar
  136. 136.
    Eid AJ, Bakri SJ, Kijpittayarit S, Razonable RR. Clinical features and outcomes of cytomegalovirus retinitis after transplantation. Transpl Infect Dis. 2008;10(1):13–8.PubMedCrossRefGoogle Scholar
  137. 137.
    Larsson K, Lonnqvist B, Ringden O, Hedquist B, Ljungman P. CMV retinitis after allogeneic bone marrow transplantation: a report of five cases. Transpl Infect Dis. 2002;4(2):75–9.PubMedCrossRefGoogle Scholar
  138. 138.
    Wolf DG, Lurain NS, Zuckerman T, Hoffman R, Satinger J, Honigman A, et al. Emergence of late cytomegalovirus central nervous system disease in hematopoietic stem cell transplant recipients. Blood. 2003;101(2):463–5.PubMedCrossRefGoogle Scholar
  139. 139.
    Ando T, Mitani N, Yamashita K, Takahashi T, Ohama E, Miyata H, et al. Cytomegalovirus ventriculoencephalitis in a reduced-intensity conditioning cord blood transplant recipient. Transpl Infect Dis. 2010;12(5):441–5.PubMedCrossRefGoogle Scholar
  140. 140.
    Reddy SM, Winston DJ, Territo MC, Schiller GJ. CMV central nervous system disease in stem-cell transplant recipients: an increasing complication of drug-resistant CMV infection and protracted immunodeficiency. Bone Marrow Transplant. 2010;45(6):979–84.PubMedCrossRefGoogle Scholar
  141. 141.
    Razonable R. Direct and indirect effects of cytomegalovirus: can we prevent them? Enferm Infecc Microbiol Clin. 2010;28(1):1–5.PubMedCrossRefGoogle Scholar
  142. 142.
    Nichols WG, Corey L, Gooley T, Davis C, Boeckh M. High risk of death due to bacterial and fungal infection among cytomegalovirus (CMV)-seronegative recipients of stem cell transplants from seropositive donors: evidence for indirect effects of primary CMV infection. J Infect Dis. 2002;185(3):273–82.PubMedCrossRefGoogle Scholar
  143. 143.
    Cantoni N, Hirsch HH, Khanna N, Gerull S, Buser A, Bucher C, et al. Evidence for a bidirectional relationship between cytomegalovirus replication and acute graft-versus-host disease. Biol Blood Marrow Transplant. 2010;16(9):1309–14.PubMedCrossRefGoogle Scholar
  144. 144.
    Jacobsen N, Andersen HK, Skinhoj P, Ryder LP, Platz P, Jerne D, et al. Correlation between donor cytomegalovirus immunity and chronic graft-versus-host disease after allogeneic bone marrow transplantation. Scand J Haematol. 1986;36(5):499–506.PubMedCrossRefGoogle Scholar
  145. 145.
    Lonnqvist B, Ringden O, Wahren B, Gahrton G, Lundgren G. Cytomegalovirus infection associated with and preceding chronic graft-versus-host disease. Transplantation. 1984;38(5):465–8.PubMedCrossRefGoogle Scholar
  146. 146.
    Helantera I, Koskinen P, Finne P, Loginov R, Kyllonen L, Salmela K, et al. Persistent cytomegalovirus infection in kidney allografts is associated with inferior graft function and survival. Transpl Int. 2006;19(11):893–900.PubMedCrossRefGoogle Scholar
  147. 147.
    Kliem V, Fricke L, Wollbrink T, Burg M, Radermacher J, Rohde F. Improvement in long-term renal graft survival due to CMV prophylaxis with oral ganciclovir: results of a randomized clinical trial. Am J Transplant. 2008;8(5):975–83.PubMedCrossRefGoogle Scholar
  148. 148.
    Reischig T, Jindra P, Hes O, Bouda M, Kormunda S, Treska V. Effect of cytomegalovirus viremia on subclinical rejection or interstitial fibrosis and tubular atrophy in protocol biopsy at 3 months in renal allograft recipients managed by preemptive therapy or antiviral prophylaxis. Transplantation. 2009;87(3):436–44.PubMedCrossRefGoogle Scholar
  149. 149.
    Snydman DR. The case for cytomegalovirus prophylaxis in solid organ transplantation. Rev Med Virol. 2006;16(5):289–95.PubMedCrossRefGoogle Scholar
  150. 150.
    Lonnqvist B, Ringden O, Ljungman P, Wahren B, Gahrton G. Reduced risk of recurrent leukaemia in bone marrow transplant recipients after cytomegalovirus infection. Br J Haematol. 1986;63(4):671–9.PubMedCrossRefGoogle Scholar
  151. 151.
    Behrendt CE, Rosenthal J, Bolotin E, Nakamura R, Zaia J, Forman SJ. Donor and recipient CMV serostatus and outcome of pediatric allogeneic HSCT for acute leukemia in the era of CMV-preemptive therapy. Biol Blood Marrow Transplant. 2009;15(1):54–60.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Elmaagacli AH, Steckel NK, Koldehoff M, Hegerfeldt Y, Trenschel R, Ditschkowski M, et al. Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients. Blood. 2011;118(5):1402–12.PubMedCrossRefGoogle Scholar
  153. 153.
    Green ML, Leisenring WM, Xie H, Walter RB, Mielcarek M, Sandmaier BM, et al. CMV reactivation after allogeneic HCT and relapse risk: evidence for early protection in acute myeloid leukemia. Blood. 2013;122(7):1316–24.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Ito S, Pophali P, Co W, Koklanaris EK, Superata J, Fahle GA, et al. CMV reactivation is associated with a lower incidence of relapse after allo-SCT for CML. Bone Marrow Transplant. 2013;48(10):1313–6.PubMedPubMedCentralCrossRefGoogle Scholar
  155. 155.
    Scheper W, van Dorp S, Kersting S, Pietersma F, Lindemans C, Hol S, et al. GammadeltaT cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia. Leukemia. 2013;27(6):1328–38.PubMedCrossRefGoogle Scholar
  156. 156.
    Foley B, Cooley S, Verneris MR, Pitt M, Curtsinger J, Luo X, et al. Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function. Blood. 2012;119(11):2665–74.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 157.
    Koldehoff M, Lindemann M, Opalka B, Bauer S, Ross RS, Elmaagacli AH. Cytomegalovirus induces apoptosis in acute leukemia cells as a virus-versus-leukemia function. Leuk Lymphoma. 2015;1–25.Google Scholar
  158. 158.
    Challa-Malladi M, Lieu YK, Califano O, Holmes AB, Bhagat G, Murty VV, et al. Combined genetic inactivation of beta2-Microglobulin and CD58 reveals frequent escape from immune recognition in diffuse large B cell lymphoma. Cancer Cell. 2011;20(6):728–40.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295(5562):2097–100.PubMedCrossRefGoogle Scholar
  160. 160.
    Schmidt-Hieber M, Labopin M, Beelen D, Volin L, Ehninger G, Finke J, et al. CMV serostatus still has an important prognostic impact in de novo acute leukemia patients after allogeneic stem cell transplantation: a report from the Acute Leukemia Working Party of EBMT. Blood. 2013;122(19):3359–64.PubMedCrossRefGoogle Scholar
  161. 161.
    George B, Pati N, Gilroy N, Ratnamohan M, Huang G, Kerridge I, et al. Pre-transplant cytomegalovirus (CMV) serostatus remains the most important determinant of CMV reactivation after allogeneic hematopoietic stem cell transplantation in the era of surveillance and preemptive therapy. Transpl Infect Dis. 2010;12(4):322–9.PubMedCrossRefGoogle Scholar
  162. 162.
    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
  163. 163.
    Pergam SA, Xie H, Sandhu R, Pollack M, Smith J, Stevens-Ayers T, et al. Efficiency and risk factors for CMV transmission in seronegative hematopoietic stem cell recipients. Biol Blood Marrow Transplant. 2012;18(9):1391–400.PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Ljungman P. The role of cytomegalovirus serostatus on outcome of hematopoietic stem cell transplantation. Curr Opin Hematol. 2014;21(6):466–9.PubMedCrossRefGoogle Scholar
  165. 165.
    Bowden RA, Sayers M, Flournoy N, Newton B, Banaji M, Thomas ED, et al. Cytomegalovirus immune globulin and seronegative blood products to prevent primary cytomegalovirus infection after marrow transplantation. N Engl J Med. 1986;314(16):1006–10.PubMedCrossRefGoogle Scholar
  166. 166.
    Ljungman P, Brand R, Hoek J, de la Camara R, Cordonnier C, Einsele H, et al. Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation. Clin Infect Dis. 2014;59(4):473–81.PubMedCrossRefGoogle Scholar
  167. 167.
    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(7):2240–5.PubMedGoogle Scholar
  168. 168.
    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(1):228–36.PubMedCrossRefGoogle Scholar
  169. 169.
    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(6):2003–8.PubMedCrossRefGoogle Scholar
  170. 170.
    Zhou W, Longmate J, Lacey SF, Palmer JM, Gallez-Hawkins G, Thao L, et al. Impact of donor CMV-status on viral infection and reconstitution of multi-function CMV-specific T-cells in CMV-positive transplant recipients. Blood. 2009;113(25):6465–76.PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Bordon V, Bravo S, Van Renterghem L, de Moerloose B, Benoit Y, Laureys G, et al. Surveillance of cytomegalovirus (CMV) DNAemia in pediatric allogeneic stem cell transplantation: incidence and outcome of CMV infection and disease. Transpl Infect Dis. 2008;10(1):19–23.PubMedCrossRefGoogle Scholar
  172. 172.
    Cwynarski K, Roberts IA, Iacobelli S, van Biezen A, Brand R, Devergie A, et al. Stem cell transplantation for chronic myeloid leukemia in children. Blood. 2003;102(4):1224–31.PubMedCrossRefGoogle Scholar
  173. 173.
    Erard V, Guthrie KA, Riddell S, Boeckh M. Impact of HLA A2 and cytomegalovirus serostatus on outcomes in patients with leukemia following matched-sibling myeloablative allogeneic hematopoietic cell transplantation. Haematologica. 2006;91(10):1377–83.PubMedGoogle Scholar
  174. 174.
    Grob JP, Grundy JE, Prentice HG, Griffiths PD, Hoffbrand AV, Hughes MD, et al. Immune donors can protect marrow-transplant recipients from severe cytomegalovirus infections. Lancet. 1987;1(8536):774–6.PubMedCrossRefGoogle Scholar
  175. 175.
    Jacobsen N, Badsberg JH, Lonnqvist B, Ringden O, Volin L, Rajantie J, et al. Graft-versus-leukaemia activity associated with CMV-seropositive donor, post-transplant CMV infection, young donor age and chronic graft-versus-host disease in bone marrow allograft recipients. The Nordic Bone Marrow Transplantation Group. Bone Marrow Transplant. 1990;5(6):413–8.PubMedGoogle Scholar
  176. 176.
    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(7):2043–51.PubMedCrossRefGoogle Scholar
  177. 177.
    Nachbaur D, Clausen J, Kircher B. Donor cytomegalovirus seropositivity and the risk of leukemic relapse after reduced-intensity transplants. Eur J Haematol. 2006;76(5):414–9.PubMedCrossRefGoogle Scholar
  178. 178.
    Gustafsson Jernberg A, Remberger M, Ringden O, Winiarski J. Risk factors in pediatric stem cell transplantation for leukemia. Pediatr Transplant. 2004;8(5):464–74.PubMedCrossRefGoogle Scholar
  179. 179.
    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;102:4255–60.PubMedCrossRefGoogle Scholar
  180. 180.
    Avetisyan G, Aschan J, Hagglund H, Ringden O, Ljungman P. Evaluation of intervention strategy based on CMV-specific immune responses after allogeneic SCT. Bone Marrow Transplant. 2007;40(9):865–9.PubMedCrossRefGoogle Scholar
  181. 181.
    Ganepola S, Gentilini C, Hilbers U, Lange T, Rieger K, Hofmann J, et al. Patients at high risk for CMV infection and disease show delayed CD8+ T-cell immune recovery after allogeneic stem cell transplantation. Bone Marrow Transplant. 2007;39(5):293–9.PubMedCrossRefGoogle Scholar
  182. 182.
    Lilleri D, Fornara C, Chiesa A, Caldera D, Alessandrino EP, Gerna G. Human cytomegalovirus-specific CD4+ and CD8+ T-cell reconstitution in adult allogeneic hematopoietic stem cell transplant recipients and immune control of viral infection. Haematologica. 2008;93(2):248–56.PubMedCrossRefGoogle Scholar
  183. 183.
    Moins-Teisserenc H, Busson M, Scieux C, Bajzik V, Cayuela JM, Clave E, et al. Patterns of cytomegalovirus reactivation are associated with distinct evolutive profiles of immune reconstitution after allogeneic hematopoeitic stem cell transplantation. J Infect Dis. 2008;198(6):818–26.PubMedCrossRefGoogle Scholar
  184. 184.
    Lin TS, Zahrieh D, Weller E, Alyea EP, Antin JH, Soiffer RJ. Risk factors for cytomegalovirus reactivation after CD6+ T-cell-depleted allogeneic bone marrow transplantation. Transplantation. 2002;74(1):49–54.PubMedCrossRefGoogle Scholar
  185. 185.
    Ozdemir E, Saliba R, Champlin R, Couriel D, Giralt S, de Lima M, et al. Risk factors associated with late cytomegalovirus reactivation after allogeneic stem cell transplantation for hematological malignancies. Bone Marrow Transplant. 2007;40(2):125–36.PubMedCrossRefGoogle Scholar
  186. 186.
    Marty FM, Bryar J, Browne SK, Schwarzberg T, Ho VT, Bassett IV, et al. Sirolimus-based graft-versus-host disease prophylaxis protects against cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation: a cohort analysis. Blood. 2007;110(2):490–500.PubMedPubMedCentralCrossRefGoogle Scholar
  187. 187.
    Ljungman P, Aschan J, Lewensohn-Fuchs I, Carlens S, Larsson K, Lonnqvist B, et al. Results of different strategies for reducing cytomegalovirus-associated mortality in allogeneic stem cell transplant recipients. Transplantation. 1998;66(10):1330–4.PubMedCrossRefGoogle Scholar
  188. 188.
    Martino R, Rovira M, Carreras E, Solano C, Jorge S, De La Rubia J, et al. Severe infections after allogeneic peripheral blood stem cell transplantation: a matched-pair comparison of unmanipulated and CD34+ cell-selected transplantation. Haematologica. 2001;86(10):1075–86.PubMedGoogle Scholar
  189. 189.
    Miller W, Flynn P, McCullough J, Balfour Jr HH, Goldman A, Haake R, et al. Cytomegalovirus infection after bone marrow transplantation: an association with acute graft-v-host disease. Blood. 1986;67(4):1162–7.PubMedGoogle Scholar
  190. 190.
    Walker CM, van Burik JA, De For TE, Weisdorf DJ. Cytomegalovirus infection after allogeneic transplantation: comparison of cord blood with peripheral blood and marrow graft sources. Biol Blood Marrow Transplant. 2007;13(9):1106–15.PubMedCrossRefGoogle Scholar
  191. 191.
    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. Blood. 1999;94(12):4029–35.PubMedGoogle Scholar
  192. 192.
    Trenschel R, Ross S, Husing J, Ottinger H, Elmaagacli A, Roggendorf M, et al. Reduced risk of persisting cytomegalovirus pp 65 antigenemia and cytomegalovirus interstitial pneumonia following allogeneic PBSCT. Bone Marrow Transplant. 2000;25(6):665–72.PubMedCrossRefGoogle Scholar
  193. 193.
    Kudchodkar SB, Yu Y, Maguire TG, Alwine JC. Human cytomegalovirus infection alters the substrate specificities and rapamycin sensitivities of raptor- and rictor-containing complexes. Proc Natl Acad Sci U S A. 2006;103(38):14182–7.PubMedPubMedCentralCrossRefGoogle Scholar
  194. 194.
    Kornblit B, Maloney DG, Storer BE, Maris MB, Vindelov L, Hari P, et al. A randomized phase II trial of tacrolimus, mycophenolate mofetil and sirolimus after non-myeloablative unrelated donor transplantation. Haematologica. 2014;99(10):1624–31.PubMedPubMedCentralCrossRefGoogle Scholar
  195. 195.
    Junghanss C, Boeckh M, Carter RA, Sandmaier BM, Maris MB, Maloney DG, et al. Incidence and outcome of cytomegalovirus infections following nonmyeloablative compared with myeloablative allogeneic stem cell transplantation, a matched control study. Blood. 2002;99(6):1978–85.PubMedCrossRefGoogle Scholar
  196. 196.
    Nakamae H, Kirby KA, Sandmaier BM, Norasetthada L, Maloney DG, Maris MB, et al. Effect of conditioning regimen intensity on CMV infection in allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2009;15(6):694–703.PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Schoemans H, Theunissen K, Maertens J, Boogaerts M, Verfaillie C, Wagner J. Adult umbilical cord blood transplantation: a comprehensive review. Bone Marrow Transplant. 2006;38(2):83–93.PubMedCrossRefGoogle Scholar
  198. 198.
    Jacobson CA, Turki AT, McDonough SM, Stevenson KE, Kim HT, Kao G, et al. Immune reconstitution after double umbilical cord blood stem cell transplantation: comparison with unrelated peripheral blood stem cell transplantation. Biol Blood Marrow Transplant. 2012;18(4):565–74.PubMedCrossRefGoogle Scholar
  199. 199.
    Montesinos P, Sanz J, Cantero S, Lorenzo I, Martin G, Saavedra S, et al. Incidence, risk factors, and outcome of cytomegalovirus infection and disease in patients receiving prophylaxis with oral valganciclovir or intravenous ganciclovir after umbilical cord blood transplantation. Biol Blood Marrow Transplant. 2009;15(6):730–40.PubMedCrossRefGoogle Scholar
  200. 200.
    Mikulska M, Raiola AM, Bruzzi P, Varaldo R, Annunziata S, Lamparelli T, et al. CMV infection after transplant from cord blood compared to other alternative donors: the importance of donor-negative CMV serostatus. Biol Blood Marrow Transplant. 2012;18(1):92–9.PubMedCrossRefGoogle Scholar
  201. 201.
    Beck JC, Wagner JE, DeFor TE, Brunstein CG, Schleiss MR, Young JA, et al. Impact of cytomegalovirus (CMV) reactivation after umbilical cord blood transplantation. Biol Blood Marrow Transplant. 2010;16(2):215–22.PubMedCrossRefGoogle Scholar
  202. 202.
    Sauter C, Abboud M, Jia X, Heller G, Gonzales AM, Lubin M, et al. Serious infection risk and immune recovery after double-unit cord blood transplantation without antithymocyte globulin. Biol Blood Marrow Transplant. 2011;17(10):1460–71.PubMedPubMedCentralCrossRefGoogle Scholar
  203. 203.
    Albano MS, Taylor P, Pass RF, Scaradavou A, Ciubotariu R, Carrier C, et al. Umbilical cord blood transplantation and cytomegalovirus: posttransplantation infection and donor screening. Blood. 2006;108(13):4275–82.PubMedCrossRefGoogle Scholar
  204. 204.
    Matsumura T, Narimatsu H, Kami M, Yuji K, Kusumi E, Hori A, et al. Cytomegalovirus infections following umbilical cord blood transplantation using reduced intensity conditioning regimens for adult patients. Biol Blood Marrow Transplant. 2007;13(5):577–83.PubMedCrossRefGoogle Scholar
  205. 205.
    Milano F, Pergam SA, Xie H, Leisenring WM, Gutman JA, Riffkin I, et al. Intensive strategy to prevent CMV disease in seropositive umbilical cord blood transplant recipients. Blood. 2011;118(20):5689–96.PubMedPubMedCentralCrossRefGoogle Scholar
  206. 206.
    Saavedra S, Sanz GF, Jarque I, Moscardo F, Jimenez C, Lorenzo I, et al. Early infections in adult patients undergoing unrelated donor cord blood transplantation. Bone Marrow Transplant. 2002;30(12):937–43.PubMedCrossRefGoogle Scholar
  207. 207.
    Takami A, Mochizuki K, Asakura H, Yamazaki H, Okumura H, Nakao S. High incidence of cytomegalovirus reactivation in adult recipients of an unrelated cord blood transplant. Haematologica. 2005;90(9):1290–2.PubMedGoogle Scholar
  208. 208.
    Tomonari A, Iseki T, Ooi J, Takahashi S, Shindo M, Ishii K, et al. Cytomegalovirus infection following unrelated cord blood transplantation for adult patients: a single institute experience in Japan. Br J Haematol. 2003;121(2):304–11.PubMedCrossRefGoogle Scholar
  209. 209.
    Reisner Y, Hagin D, Martelli MF. Haploidentical hematopoietic transplantation: current status and future perspectives. Blood. 2011;118(23):6006–17.PubMedCrossRefGoogle Scholar
  210. 210.
    Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F, et al. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med. 1998;339(17):1186–93.PubMedCrossRefGoogle Scholar
  211. 211.
    Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, et al. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol. 2005;23(15):3447–54.PubMedCrossRefGoogle Scholar
  212. 212.
    Mehta J, Singhal S, Gee AP, Chiang KY, Godder K, Rhee Fv F, et al. Bone marrow transplantation from partially HLA-mismatched family donors for acute leukemia: single-center experience of 201 patients. Bone Marrow Transplant. 2004;33(4):389–96.PubMedCrossRefGoogle Scholar
  213. 213.
    Shmueli E, Or R, Shapira MY, Resnick IB, Caplan O, Bdolah-Abram T, et al. High rate of cytomegalovirus drug resistance among patients receiving preemptive antiviral treatment after haploidentical stem cell transplantation. J Infect Dis. 2014;209(4):557–61.PubMedCrossRefGoogle Scholar
  214. 214.
    Luznik L, O’Donnell PV, Fuchs EJ. Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation. Semin Oncol. 2012;39(6):683–93.PubMedCrossRefGoogle Scholar
  215. 215.
    Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14(6):641–50.PubMedPubMedCentralCrossRefGoogle Scholar
  216. 216.
    Raiola AM, Dominietto A, di Grazia C, Lamparelli T, Gualandi F, Ibatici A, et al. Unmanipulated haploidentical transplants compared with other alternative donors and matched sibling grafts. Biol Blood Marrow Transplant. 2014;20(10):1573–9.PubMedCrossRefGoogle Scholar
  217. 217.
    Boeckh M, Stevens-Ayers T, Bowden RA. Cytomegalovirus pp 65 antigenemia after autologous marrow and peripheral blood stem cell transplantation. J Infect Dis. 1996;174(5):907–12.PubMedCrossRefGoogle Scholar
  218. 218.
    Hebart H, Schroder A, Loffler J, Klingebiel T, Martin H, Wassmann B, et al. Cytomegalovirus monitoring by polymerase chain reaction of whole blood samples from patients undergoing autologous bone marrow or peripheral blood progenitor cell transplantation. J Infect Dis. 1997;175(6):1490–3.PubMedCrossRefGoogle Scholar
  219. 219.
    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(1):69–73.PubMedCrossRefGoogle Scholar
  220. 220.
    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(4):939–43.PubMedCrossRefGoogle Scholar
  221. 221.
    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(6):835–8.PubMedCrossRefGoogle Scholar
  222. 222.
    Enright H, Haake R, Weisdorf D, Ramsay N, McGlave P, Kersey J, et al. Cytomegalovirus pneumonia after bone marrow transplantation. Risk factors and response to therapy. Transplantation. 1993;55(6):1339–46.PubMedCrossRefGoogle Scholar
  223. 223.
    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(9):1888–94.PubMedGoogle Scholar
  224. 224.
    Einsele H, Steidle M, Vallbracht A, Saal JG, Ehninger G, Muller CA. Early occurrence of human cytomegalovirus infection after bone marrow transplantation as demonstrated by the polymerase chain reaction technique. Blood. 1991;77(5):1104–10.PubMedGoogle Scholar
  225. 225.
    Nguyen Q, Champlin R, Giralt S, Rolston K, Raad I, Jacobson K, et al. Late cytomegalovirus pneumonia in adult allogeneic blood and marrow transplant recipients. Clin Infect Dis. 1999;28(3):618–23.PubMedCrossRefGoogle Scholar
  226. 226.
    Perez-Bercoff L, Vudattu NK, Byrareddy SN, Mattsson J, Maeurer M, Ljungman P. Reduced IL-7 responsiveness defined by signal transducer and activator of transcription 5 phosphorylation in T cells may be a marker for increased risk of developing cytomegalovirus disease in patients after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20(1):128–32.PubMedCrossRefGoogle Scholar
  227. 227.
    Salzberger B, Bowden RA, Hackman RC, Davis C, Boeckh M. Neutropenia in allogeneic marrow transplant recipients receiving ganciclovir for prevention of cytomegalovirus disease: risk factors and outcome. Blood. 1997;90(6):2502–8.PubMedGoogle Scholar
  228. 228.
    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(3):173–8.PubMedCrossRefGoogle Scholar
  229. 229.
    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(7):3002–8.PubMedCrossRefGoogle Scholar
  230. 230.
    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(6):635–40.PubMedCrossRefGoogle Scholar
  231. 231.
    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(4):1159–64.PubMedCrossRefGoogle Scholar
  232. 232.
    Lurain NS, Chou S. Antiviral drug resistance of human cytomegalovirus. Clin Microbiol Rev. 2010;23(4):689–712.PubMedPubMedCentralCrossRefGoogle Scholar
  233. 233.
    Drew WL. Is combination antiviral therapy for CMV superior to monotherapy? J Clin Virol. 2006;35(4):485–8.PubMedCrossRefGoogle Scholar
  234. 234.
    Biron KK, Harvey RJ, Chamberlain SC, Good SS, Smith 3rd AA, Davis MG, et al. Potent and selective inhibition of human cytomegalovirus replication by 1263W94, a benzimidazole L-riboside with a unique mode of action. Antimicrob Agents Chemother. 2002;46(8):2365–72.PubMedPubMedCentralCrossRefGoogle Scholar
  235. 235.
    Drew WL, Miner RC, Marousek GI, Chou S. Maribavir sensitivity of cytomegalovirus isolates resistant to ganciclovir, cidofovir or foscarnet. J Clin Virol. 2006;37(2):124–7.PubMedCrossRefGoogle Scholar
  236. 236.
    Chou S, Marousek GI. Maribavir antagonizes the antiviral action of ganciclovir on human cytomegalovirus. Antimicrob Agents Chemother. 2006;50(10):3470–2.PubMedPubMedCentralCrossRefGoogle Scholar
  237. 237.
    Marty FM, Ljungman P, Papanicolaou GA, Winston DJ, Chemaly RF, Strasfeld L, et al. Maribavir prophylaxis for prevention of cytomegalovirus disease in recipients of allogeneic stem-cell transplants: a phase 3, double-blind, placebo-controlled, randomised trial. Lancet Infect Dis. 2011;11(4):284–92.PubMedCrossRefGoogle Scholar
  238. 238.
    Wang LH, Peck RW, Yin Y, Allanson J, Wiggs R, Wire MB. Phase I safety and pharmacokinetic trials of 1263W94, a novel oral anti-human cytomegalovirus agent, in healthy and human immunodeficiency virus-infected subjects. Antimicrob Agents Chemother. 2003;47(4):1334–42.PubMedPubMedCentralCrossRefGoogle Scholar
  239. 239.
    Winston DJ, Young JA, Pullarkat V, Papanicolaou GA, Vij R, Vance E, et al. Maribavir prophylaxis for prevention of cytomegalovirus infection in allogeneic stem-cell transplant recipients: a multicenter, randomized, double-blind, placebo-controlled, dose-ranging study. Blood. 2008;111:5403–10.PubMedPubMedCentralCrossRefGoogle Scholar
  240. 240.
    Marty FM, Boeckh M. Maribavir and human cytomegalovirus—what happened in the clinical trials and why might the drug have failed? Curr Opin Virol. 2011;1(6):555–62.PubMedCrossRefGoogle Scholar
  241. 241.
    Alain S, Revest M, Veyer D, Essig M, Rerolles JP, Rawlinson W, et al. Maribavir use in practice for cytomegalovirus infection in French transplantation centers. Transplant Proc. 2013;45(4):1603–7.PubMedCrossRefGoogle Scholar
  242. 242.
    Avery RK, Marty FM, Strasfeld L, Lee I, Arrieta A, Chou S, et al. Oral maribavir for treatment of refractory or resistant cytomegalovirus infections in transplant recipients. Transpl Infect Dis. 2010;12(6):489–96.PubMedCrossRefGoogle Scholar
  243. 243.
    Schubert A, Ehlert K, Schuler-Luettmann S, Gentner E, Mertens T, Michel D. Fast selection of maribavir resistant cytomegalovirus in a bone marrow transplant recipient. BMC Infect Dis. 2013;13:330.PubMedPubMedCentralCrossRefGoogle Scholar
  244. 244.
    Strasfeld L, Lee I, Villano S, Chou S. Virologic characterization of multi-drug-resistant cytomegalovirus infection in two transplant recipients treated with maribavir. J Infect Dis. 2010;202(1):104–8.PubMedCrossRefGoogle Scholar
  245. 245.
    Lischka P, Hewlett G, Wunberg T, Baumeister J, Paulsen D, Goldner T, et al. In vitro and in vivo activities of the novel anticytomegalovirus compound AIC246. Antimicrob Agents Chemother. 2010;54(3):1290–7.PubMedPubMedCentralCrossRefGoogle Scholar
  246. 246.
    Kaul DR, Stoelben S, Cober E, Ojo T, Sandusky E, Lischka P, et al. First report of successful treatment of multidrug-resistant cytomegalovirus disease with the novel anti-CMV compound AIC246. Am J Transplant. 2011;11(5):1079–84.PubMedCrossRefGoogle Scholar
  247. 247.
    Chemaly RF, Ullmann AJ, Stoelben S, Richard MP, Bornhauser M, Groth C, et al. Letermovir for cytomegalovirus prophylaxis in hematopoietic-cell transplantation. N Engl J Med. 2014;370(19):1781–9.PubMedCrossRefGoogle Scholar
  248. 248.
    Goldner T, Hempel C, Ruebsamen-Schaeff H, Zimmermann H, Lischka P. Geno- and phenotypic characterization of human cytomegalovirus mutants selected in vitro after letermovir (AIC246) exposure. Antimicrob Agents Chemother. 2014;58(1):610–3.PubMedPubMedCentralCrossRefGoogle Scholar
  249. 249.
    Wildum S, Zimmermann H, Lischka P. In vitro drug combination studies of Letermovir (AIC246, MK-8228) with approved anti-human cytomegalovirus (HCMV) and anti-HIV compounds in inhibition of HCMV and HIV replication. Antimicrob Agents Chemother. 2015;59(6):3140–8.PubMedPubMedCentralCrossRefGoogle Scholar
  250. 250.
    Dropulic LK, Cohen JI. Update on new antivirals under development for the treatment of double-stranded DNA virus infections. Clin Pharmacol Ther. 2010;88(5):610–9.PubMedPubMedCentralCrossRefGoogle Scholar
  251. 251.
    Marty FM, Winston DJ, Rowley SD, Vance E, Papanicolaou GA, Mullane KM, et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013;369(13):1227–36.PubMedCrossRefGoogle Scholar
  252. 252.
    Hakki M, Chou S. The biology of cytomegalovirus drug resistance. Curr Opin Infect Dis. 2011;24(6):605–11.PubMedPubMedCentralCrossRefGoogle Scholar
  253. 253.
    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(12):1071–5.PubMedCrossRefGoogle Scholar
  254. 254.
    Efferth T, Marschall M, Wang X, Huong SM, Hauber I, Olbrich A, et al. Antiviral activity of artesunate towards wild-type, recombinant, and ganciclovir-resistant human cytomegaloviruses. J Mol Med. 2002;80(4):233–42.PubMedCrossRefGoogle Scholar
  255. 255.
    Efferth T, Romero MR, Wolf DG, Stamminger T, Marin JJ, Marschall M. The antiviral activities of artemisinin and artesunate. Clin Infect Dis. 2008;47(6):804–11.PubMedCrossRefGoogle Scholar
  256. 256.
    Kudchodkar SB, Yu Y, Maguire TG, Alwine JC. Human cytomegalovirus infection induces rapamycin-insensitive phosphorylation of downstream effectors of mTOR kinase. J VIrol. 2004;78(20):11030–9.PubMedPubMedCentralCrossRefGoogle Scholar
  257. 257.
    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;86:3598–603.PubMedGoogle Scholar
  258. 258.
    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(5):347–50.PubMedCrossRefGoogle Scholar
  259. 259.
    Nichols WG, Price TH, Gooley T, Corey L, Boeckh M. Transfusion-transmitted cytomegalovirus infection after receipt of leukoreduced blood products. Blood. 2003;101(10):4195–200.PubMedCrossRefGoogle Scholar
  260. 260.
    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):1–20.PubMedCrossRefGoogle Scholar
  261. 261.
    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(10):1310–9.PubMedCrossRefGoogle Scholar
  262. 262.
    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(3):483–7.PubMedCrossRefGoogle Scholar
  263. 263.
    Ruutu T, Ljungman P, Brinch L, Lenhoff S, Lonnqvist B, Ringden O, et al. No prevention of cytomegalovirus infection by anti-cytomegalovirus hyperimmune globulin in seronegative bone marrow transplant recipients. The Nordic BMT Group. Bone Marrow Transplant. 1997;19(3):233–6.PubMedCrossRefGoogle Scholar
  264. 264.
    Boeckh M, Bowden R, Storer B, Chao N, Spielberger R, Tierney D, et al. Randomized, placebo-controlled, double-blind study of a cytomegalovirus-specific monoclonal antibody (MSL-109) for prevention of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2001;7(6):343–51.PubMedCrossRefGoogle Scholar
  265. 265.
    Bass E, Powe N, Goodman S, Graziano S, Griffiths R, Kickler T, et al. Efficacy of immune globulin in preventing complications of bone marrow transplantation: a meta-analysis. Bone Marrow Transplant. 1993;12:179–83.Google Scholar
  266. 266.
    Messori A, Rampazzo R, Scroccaro G, Martini N. Efficacy of hyperimmune anti-cytomegalovirus immunoglobulins for the prevention of cytomegalovirus infection in recipients of allogeneic bone marrow transplantation: a meta analysis. Bone Marrow Transplant. 1994;13:163–8.PubMedGoogle Scholar
  267. 267.
    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
  268. 268.
    Sullivan KM, Kopecky KJ, Jocom J, Fisher L, Buckner CD, Meyers JD, et al. Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation. N Engl J Med. 1990;323(11):705–12.PubMedCrossRefGoogle Scholar
  269. 269.
    Winston DJ, Ho WG, Lin CH, Bartoni K, Budinger MD, Gale RP, et al. Intravenous immune globulin for prevention of cytomegalovirus infection and interstitial pneumonia after bone marrow transplantation. Ann Intern Med. 1987;106(1):12–8.PubMedCrossRefGoogle Scholar
  270. 270.
    Zikos P, Van Lint MT, Lamparelli T, Gualandi F, Occhini D, Mordini N, et al. A randomized trial of high dose polyvalent intravenous immunoglobulin (HDIgG) vs. Cytomegalovirus (CMV) hyperimmune IgG in allogeneic hemopoietic stem cell transplants (HSCT). Haematologica. 1998;83(2):132–7.PubMedGoogle Scholar
  271. 271.
    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
  272. 272.
    Boeckh M, Nichols WG, Chemaly RF, Papanicolaou GA, Wingard JR, Xie H, et al. Valganciclovir for the prevention of complications of late cytomegalovirus infection after allogeneic hematopoietic cell transplantation: a randomized trial. Ann Intern Med. 2015;162(1):1–10.PubMedPubMedCentralCrossRefGoogle Scholar
  273. 273.
    Pollack M, Heugel J, Xie H, Leisenring W, Storek J, Young JA, et al. An international comparison of current strategies to prevent herpesvirus and fungal infections in hematopoietic cell transplant recipients. Biol Blood Marrow Transplant. 2011;17(5):664–73.PubMedCrossRefGoogle Scholar
  274. 274.
    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;73:930–6.Google Scholar
  275. 275.
    Meyers JD, Reed EC, Shepp DH, Thornquist M, Dandliker PS, Vicary CA, et al. Acyclovir for prevention of cytomegalovirus infection and disease after allogeneic marrow transplantation. N Engl J Med. 1988;318(2):70–5.PubMedCrossRefGoogle Scholar
  276. 276.
    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(8900):749–53.PubMedCrossRefGoogle Scholar
  277. 277.
    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(3):179–84.PubMedCrossRefGoogle Scholar
  278. 278.
    Peggs KS, Preiser W, Kottaridis PD, McKeag N, Brink NS, Tedder RS, et al. Extended routine polymerase chain reaction surveillance and pre-emptive antiviral therapy for cytomegalovirus after allogeneic transplantation. Br J Haematol. 2000;111(3):782–90.PubMedGoogle Scholar
  279. 279.
    Nichols WG, Price T, Boeckh M. Donor serostatus and CMV infection and disease among recipients of prophylactic granulocyte transfusions. Blood. 2003;101(12):5091–2. author reply 2.PubMedCrossRefGoogle Scholar
  280. 280.
    Lilleri D, Gerna G, Furione M, Bernardo ME, Giorgiani G, Telli S, et al. Use of a DNAemia cut-off for monitoring human cytomegalovirus infection reduces the number of preemptively treated children and young adults receiving hematopoietic stem-cell transplantation compared with qualitative pp65 antigenemia. Blood. 2007;110(7):2757–60.PubMedCrossRefGoogle Scholar
  281. 281.
    Pang XL, Fox JD, Fenton JM, Miller GG, Caliendo AM, Preiksaitis JK. Interlaboratory comparison of cytomegalovirus viral load assays. Am J Transplant. 2009;9(2):258–68.PubMedCrossRefGoogle Scholar
  282. 282.
    Kraft CS, Armstrong WS, Caliendo AM. Interpreting quantitative cytomegalovirus DNA testing: understanding the laboratory perspective. Clin Infect Dis. 2012;54(12):1793–7.PubMedPubMedCentralCrossRefGoogle Scholar
  283. 283.
    Ruiz-Camps I, Len O, de la Camara R, Gurgui M, Martino R, Jarque I, et al. Valganciclovir as pre-emptive therapy for cytomegalovirus infection in allogeneic haematopoietic stem cell transplant recipients. Antivir Ther. 2011;16(7):951–7.PubMedCrossRefGoogle Scholar
  284. 284.
    Allice T, Busca A, Locatelli F, Falda M, Pittaluga F, Ghisetti V. Valganciclovir as pre-emptive therapy for cytomegalovirus infection post-allogenic stem cell transplantation: implications for the emergence of drug-resistant cytomegalovirus. J Antimicrob Chemother. 2009;63(3):600–8.PubMedCrossRefGoogle Scholar
  285. 285.
    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(9):851–6.PubMedCrossRefGoogle Scholar
  286. 286.
    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(2):102–7.PubMedCrossRefGoogle Scholar
  287. 287.
    Takenaka K, Eto T, Nagafuji K, Kamezaki K, Matsuo Y, Yoshimoto G, et al. Oral valganciclovir as preemptive therapy is effective for cytomegalovirus infection in allogeneic hematopoietic stem cell transplant recipients. Int J Hematol. 2009;89(2):231–7.PubMedCrossRefGoogle Scholar
  288. 288.
    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(7):693–8.PubMedCrossRefGoogle Scholar
  289. 289.
    Volin L, Barkholt L, Nihtinen A, Aschan J, Uotinen H, Hagglund 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. 34th Annual Meeting of the European Group for Blood and Marrow Transplantation, March 30–April 2. Florence, Italy, 2008Google Scholar
  290. 290.
    Lacey SF, Diamond DJ, Zaia JA. Assessment of cellular immunity to human cytomegalovirus in recipients of allogeneic stem cell transplants. Biol Blood Marrow Transplant. 2004;10(7):433–47.PubMedCrossRefGoogle Scholar
  291. 291.
    Arvin AM, Fast P, Myers M, Plotkin S, Rabinovich R. Vaccine development to prevent cytomegalovirus disease: report from the National Vaccine Advisory Committee. Clin Infect Dis. 2004;39(2):233–9.PubMedCrossRefGoogle Scholar
  292. 292.
    Adler SP. Human CMV, vaccine trials: what if CMV caused a rash? J Clin Virol. 2008;41(3):231–6.PubMedCrossRefGoogle Scholar
  293. 293.
    Kharfan-Dabaja MA, Boeckh M, Wilck MB, Langston AA, Chu AH, Wloch MK, et al. A novel therapeutic cytomegalovirus DNA vaccine in allogeneic haemopoietic stem-cell transplantation: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis. 2012;12(4):290–9.PubMedCrossRefGoogle Scholar
  294. 294.
    La Rosa C, Longmate J, Lacey SF, Kaltcheva T, Sharan R, Marsano D, et al. Clinical evaluation of safety and immunogenicity of PADRE-cytomegalovirus (CMV) and tetanus-CMV fusion peptide vaccines with or without PF03512676 adjuvant. J Infect Dis. 2012;205(8):1294–304.PubMedPubMedCentralCrossRefGoogle Scholar
  295. 295.
    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(2):136–48.PubMedCrossRefGoogle Scholar
  296. 296.
    Parody R, Martino R, Rovira M, Vazquez L, Vazquez MJ, de la Camara R, et al. Severe infections after unrelated donor allogeneic hematopoietic stem cell transplantation in adults: comparison of cord blood transplantation with peripheral blood and bone marrow transplantation. Biol Blood Marrow Transplant. 2006;12(7):734–48.PubMedCrossRefGoogle Scholar
  297. 297.
    Tomonari A, Takahashi S, Ooi J, Tsukada N, Konuma T, Kobayashi T, et al. Preemptive therapy with ganciclovir 5 mg/kg once daily for cytomegalovirus infection after unrelated cord blood transplantation. Bone Marrow Transplant. 2008;41(4):371–6.PubMedCrossRefGoogle Scholar
  298. 298.
    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(7):505–10.PubMedCrossRefGoogle Scholar
  299. 299.
    Asberg A, Humar A, Rollag H, Jardine AG, Mouas H, Pescovitz MD, et al. Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2007;7(9):2106–13.PubMedCrossRefGoogle Scholar
  300. 300.
    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(4):831–5.PubMedCrossRefGoogle Scholar
  301. 301.
    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(5):473–6.PubMedCrossRefGoogle Scholar
  302. 302.
    Emanuel D, Cunningham I, Jules-Elysee K, 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(10):777–82.PubMedCrossRefGoogle Scholar
  303. 303.
    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(10):783–8.PubMedCrossRefGoogle Scholar
  304. 304.
    Alexander BT, Hladnik LM, Augustin KM, Casabar E, McKinnon PS, Reichley RM, et al. Use of cytomegalovirus intravenous immune globulin for the adjunctive treatment of cytomegalovirus in hematopoietic stem cell transplant recipients. Pharmacotherapy. 2010;30(6):554–61.PubMedPubMedCentralCrossRefGoogle Scholar
  305. 305.
    Chang M, Dunn JP. Ganciclovir implant in the treatment of cytomegalovirus retinitis. Expert Rev Med Devices. 2005;2(4):421–7.PubMedCrossRefGoogle Scholar
  306. 306.
    Ganly PS, Arthur C, Goldman JM, Schulenburg WE. Foscarnet as treatment for cytomegalovirus retinitis following bone marrow transplantation. Postgrad Med J. 1988;64(751):389–91.PubMedPubMedCentralCrossRefGoogle Scholar
  307. 307.
    Okamoto T, Okada M, Mori A, Saheki K, Takatsuka H, Wada H, et al. Successful treatment of severe cytomegalovirus retinitis with foscarnet and intraocular infection of ganciclovir in a myelosuppressed unrelated bone marrow transplant patient. Bone Marrow Transplant. 1997;20(9):801–3.PubMedCrossRefGoogle Scholar
  308. 308.
    Heslop HE, Leen AM. T-cell therapy for viral infections. Hematol Am Soc Hematol Educ Program. 2013;2013:342–7.Google Scholar

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© 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.Division of Infectious Diseases, Department of Internal MedicineOregon Health and Science UniversityPortlandUSA
  2. 2.Department of HematologyKarolinska University HospitalStockholmSweden

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