Biology of Blood and Marrow Transplantation
Volume 9, Issue 9 , Pages 543-558 , September 2003

Cytomegalovirus in hematopoietic stem cell transplant recipients: current status, known challenges, and future strategies

  • Michael Boeckh

      Affiliations

    • Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, Washington, USA
    • Corresponding Author InformationCorrespondence and reprint requests: Michael Boeckh, MD, Program in Infectious Diseases, Fred Hutchinson Cancer Research Center, P.O. Box 19024, Seattle, WA 8109–1024, USA
  • ,
  • W.Garrett Nichols

      Affiliations

    • Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, Washington, USA
  • ,
  • Genovefa Papanicolaou

      Affiliations

    • Memorial Sloan-Kettering Cancer Center, New York, New York, USA
  • ,
  • Robert Rubin

      Affiliations

    • Harvard Medical School, Brigham and Women’s Hospital and Harvard/Massachusetts Institute of Technology, Division of Health Sciences and Technology, Boston, Massachusetts, USA
  • ,
  • John R Wingard

      Affiliations

    • University of Florida College of Medicine, Gainesville, Florida, USA
  • ,
  • John Zaia

      Affiliations

    • City of Hope National Medical Center and Beckman Research Institute, Duarte, California, USA

Received 17 July 2003 ,Accepted 1 August 2003.

References 

  1. Bueno J, Ramil C, Green M. Current management strategies for the prevention and treatment of cytomegalovirus infection in pediatric transplant recipients. Paediatr Drugs. 2002;4:279–290
  2. Ljungman P. Beta-herpes virus challenges in the transplant recipient. J Infect Dis. 2002;186:S99–S109
  3. Boeckh M, Boivin G. Quantitation of cytomegalovirus (methodologic aspects and clinical applications). Clin Microbiol Rev. 1998;11:533–554
  4. Boeckh M, Nichols WG, Marr KA. Long-term care after hematopoietic-cell transplantation in adults. N Engl J Med. 2002;347:1625–1626
  5. Hambach L, Stadler M, Dammann E, Ganser A, Hertenstein B. Increased risk of complicated CMV infection with the use of mycophenolate mofetil in allogeneic stem cell transplantation. Bone Marrow Transplant. 2002;29:903–906
  6. Armstrong D, Cohen J. Infectious Diseases. Philadelphia, PA: Mosby; 1999;
  7. Boeckh M, Leisenring W, Riddell SR, 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
  8. 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
  9. Einsele H, Ehninger G, Hebart H, 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;86:2815–2820
  10. Einsele H, Hebart H, Kauffmann-Schneider C, et al.  Risk factors for treatment failures in patients receiving PCR-based preemptive therapy for CMV infection. Bone Marrow Transplant. 2000;25:757–763
  11. Nguyen Q, Champlin R, Giralt S, et al.  Late cytomegalovirus pneumonia in adult allogeneic blood and marrow transplant recipients. Clin Infect Dis. 1999;28:618–623
  12. Zaia JA, Schmidt GM, Chao NJ, et al.  Preemptive ganciclovir administration based solely on asymptomatic pulmonary cytomegalovirus infection in allogeneic bone marrow transplant recipients (long-term follow-up). Biol Blood Marrow Transplant. 1995;1:88–93
  13. Broers AE, van Der Holt R, van Esser JW, 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
  14. Castro-Malaspina H, Harris RE, Gajewski J, et al.  Unrelated donor marrow transplantation for myelodysplastic syndromes (outcome analysis in 510 transplants facilitated by the National Marrow Donor Program). Blood. 2002;99:1943–1951
  15. Craddock C, Szydlo RM, Dazzi F, 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
  16. Ljungman PT, Brand R, Einsele H, Frassoni F, Niederwieser D, Cordonnier C. Donor CMV serological status and outcome of CMV seropositive recipients after unrelated donor stem cell transplantation: an EBMT megafile analysis. Blood. In press.
  17. 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
  18. 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;185:273–282
  19. Kroger N, Zabelina T, Kruger W, et al.  Patient cytomegalovirus seropositivity with or without reactivation is the most important prognostic factor for survival and treatment-related mortality in stem cell transplantation from unrelated donors using pretransplant in vivo T-cell depletion with anti-thymocyte globulin. Br J Haematol. 2001;113:1060–1071
  20. Cornelissen JJ, Carston M, Kollman C, et al.  Unrelated marrow transplantation for adult patients with poor-risk acute lymphoblastic leukemia (strong graft-versus-leukemia effect and risk factors determining outcome). Blood. 2001;97:1572–1577
  21. McGlave PB, Shu XO, Wen W, et al.  Unrelated donor marrow transplantation for chronic myelogenous leukemia (9 years’ experience of the national marrow donor program). Blood. 2000;95:2219–2225
  22. Ljungman P, Aschan J, Lewensohn-Fuchs I, et al.  Results of different strategies for reducing cytomegalovirus-associated mortality in allogeneic stem cell transplant recipients. Transplantation. 1998;66:1330–1334
  23. Boeckh M, Storer B, Bensinger W, Blume K. CMV infection and disease after marrow vs. PBSC transplantation (results from a randomized trial). Blood. 2001;98: (abstr. 2006)
  24. Burt RK, Drobyski W, Seregina T, et al.  Anti-tumor effectiveness of herpes simplex thymidine kinase gene transduced donor lymphocyte infusions for relapsed hematologic malignancies following allogeneic hematopoietic stem cell transplantation. Blood. 2001;98: (abstr. 2917)
  25. Holmberg LA, Boeckh M, Hooper H, et al.  Increased incidence of cytomegalovirus disease after autologous CD34-selected peripheral blood stem cell transplantation. Blood. 1999;94:4029–4035
  26. Trenschel R, Ross S, Husing J, et al.  Reduced risk of persisting cytomegalovirus pp65 antigenemia and cytomegalovirus interstitial pneumonia following allogeneic PBSCT. Bone Marrow Transplant. 2000;25:665–672
  27. Junghanss C, Boeckh M, Carter RA, et al.  Incidence and outcome of cytomegalovirus infections following nonmyeloablative compared with myeloablative allogeneic stem cell transplantation, a matched control study. Blood. 2002;99:1978–1985
  28. Junghanss C, Storb R, Maris MB, et al. Impact of unrelated donor status on the incidence and outcome of CMV infection after nonmyeloablative allogeneic stem cell transplantation. Br J Haematol. In press.
  29. Chakrabarti S, Mackinnon S, Chopra R, et al.  High incidence of cytomegalovirus infection after nonmyeloablative stem cell transplantation (potential role of Campath-1H in delaying immune reconstitution). Blood. 2002;99:4357–4363
  30. Rubin RH. Clinical approach to infection in the compromised host. In:  Rubin RH,  Young LS editor. Infection in the Organ Transplant Recipient. New York, NY: Kluwer Academic Press; 2002;p. 573–679
  31. Hebart H, Brugger W, Grigoleit U, et al.  Risk for cytomegalovirus disease in patients receiving polymerase chain reaction-based preemptive antiviral therapy after allogeneic stem cell transplantation depends on transplantation modality. Blood. 2001;97:2183–2185
  32. 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
  33. Emery VC, Cope AV, Bowen EF, Gor D, Griffiths PD. The dynamics of human cytomegalovirus replication in vivo. J Exp Med. 1999;190:177–182
  34. Gor D, Sabin C, Prentice HG, 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;21:597–605
  35. Nichols WG, Corey L, Gooley T, 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
  36. Hansen JA, Gooley TA, Martin PJ, et al.  Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med. 1998;338:962–968
  37. Peggs KS, Preiser W, Kottaridis PD, et al.  Extended routine polymerase chain reaction surveillance and pre-emptive antiviral therapy for cytomegalovirus after allogeneic transplantation. Br J Haematol. 2000;111:782–790
  38. Boeckh M, Ljungman P. Cytomegalovirus infection after BMT. In:  Bowden RA,  Ljungman P editor. Transplant Infection. Philadelphia: Lippincott Williams & Wilkins; 1998;p. 215–227
  39. 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
  40. Ljungman P, Larsson K, Kumlien G, 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
  41. Wolf DG, Lurain NS, Zuckerman T, et al.  Emergence of late cytomegalovirus central nervous system disease in hematopoietic stem cell transplant recipients. Blood. 2003;101:463–465
  42. Ljungman P, Griffiths P, Paya C. Definitions of cytomegalovirus infection and disease in transplant recipients. Clin Infect Dis. 2002;34:1094–1097
  43. Lowance D, Neumayer HH, Legendre CM, et al.  Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. N Engl J Med. 1999;340:1462–1470
  44. Valantine HA, Gao SZ, Menon SG, et al.  Impact of prophylactic immediate posttransplant ganciclovir on development of transplant atherosclerosis (a post hoc analysis of a randomized, placebo-controlled study). Circulation. 1999;100:61–66
  45. Nichols WG, Boeckh M, Carter RA, Wald A, Corey L. Transferred herpes simplex virus immunity after stem-cell transplantation (clinical implications). J Infect Dis. 2003;187:801–808
  46. George MJ, Snydman DR, Werner BG, et al.  The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, Maryland. Am J Med. 1997;103:106–113
  47. Prentice HG, Gluckman E, Powles RL, 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
  48. Gerna G, Lilleri D, Baldanti F, et al.  Human cytomegalovirus immediate early-mRNAemia vs pp65-antigenemia for guiding pre-emptive therapy in children and young adults given hematopoietic stem cell transplantation (a prospective, randomized, open-label trial). Blood. 2003;101:5053–5060
  49. Boeckh M, Huang ML, Ferrenberg J, et al. Optimization of quantitative detection of cytomegalovirus DNA in plasma by real-time PCR. J Clin Microbiol. In press.
  50. Kaiser L, Perrin L, Chapuis B, et al.  Improved monitoring of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation by an ultrasensitive plasma DNA PCR assay. J Clin Microbiol. 2002;40:4251–4255
  51. Machado CM, Dulley FL, Boas LS, et al.  CMV pneumonia in allogeneic BMT recipients undergoing early treatment of pre-emptive ganciclovir therapy. Bone Marrow Transplant. 2000;26:413–417
  52. Emery VC, Hassan-Walker AF, Burroughs AK, Griffiths PD. Human cytomegalovirus (HCMV) replication dynamics in HCMV-naive and -experienced immunocompromised hosts. J Infect Dis. 2002;185:1723–1728
  53. Boeckh M, Bowden RA, Gooley T, Myerson D, Corey L. Successful modification of a pp65 antigenemia-based early treatment strategy for prevention of cytomegalovirus disease in allogeneic marrow transplant recipients. Blood. 1999;93:1781–1782
  54. Nichols WG, Boeckh M. Recent advances in the therapy and prevention of CMV infections. J Clin Virol. 2000;16:25–40
  55. Bowden RA, Slichter SJ, Sayers M, et al.  A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative blood products for the prevention of transfusion-associated CMV infection after marrow transplant. Blood. 1995;86:3598–3603
  56. 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
  57. Centers for Disease Control and Prevention Infectious Diseases Society of America American Society of Blood and Marrow Transplantation . Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant. 2000;6:659–713
  58. Zaia JA. Prevention of cytomegalovirus disease in hematopoietic stem cell transplantation. Clin Infect Dis. 2002;35:999–1004
  59. 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. J Infect Dis. 1991;164:483–487
  60. Ruutu T, Ljungman P, Brinch L, 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;19:233–236
  61. Bass EB, Powe NR, Goodman SN, et al.  Efficacy of immune globulin in preventing complications of bone marrow transplantation (a meta-analysis). Bone Marrow Transplant. 1993;12:273–282
  62. Guglielmo BJ, Wong-Beringer A, Linker CA. Immune globulin therapy in allogeneic bone marrow transplant (a critical review). Bone Marrow Transplant. 1994;13:499–510
  63. 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;13:163–167
  64. Zikos P, Van Lint MT, Lamparelli T, 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;83:132–137
  65. Boeckh M, Bowden RA, Storer B, 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;7:343–351
  66. Meyers JD. Prevention and treatment of cytomegalovirus infection after marrow transplantation. Bone Marrow Transplant. 1988;3:95–104
  67. Prentice HG, Gluckman E, Powles RL, et al.  Long-term survival in allogeneic bone marrow transplant recipients following acyclovir prophylaxis for CMV infection. The European Acyclovir for CMV Prophylaxis Study Group. Bone Marrow Transplant. 1997;19:129–133
  68. Ljungman P, de La Camara R, Milpied N, et al.  Randomized study of valacyclovir as prophylaxis against cytomegalovirus reactivation in recipients of allogeneic bone marrow transplants. Blood. 2002;99:3050–3056
  69. Winston DJ, Yeager AM, Chandrasekar PH, et al.  Randomized comparison of oral vancyclovir and intravenous ganciclovir for prevention of cytomegalovirus disease after allogeneic bone marrow transplantation. Clin Infect Dis. 2003;36:749–758
  70. 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
  71. Winston DJ, Ho WG, Bartoni K, 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
  72. Goodrich JM, Mori M, Gleaves CA, et al.  Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N Engl J Med. 1991;325:1601–1607
  73. Reusser P, Gambertoglio JG, Lilleby K, Meyers JD. Phase I-II trial of foscarnet for prevention of cytomegalovirus infection in autologous and allogeneic marrow transplant recipients. J Infect Dis. 1992;166:473–479
  74. Bregante S, Bertilson S, Tedone E, et al.  Foscarnet prophylaxis of cytomegalovirus infections in patients undergoing allogeneic bone marrow transplantation (BMT) (a dose-finding study). Bone Marrow Transplant. 2000;26:23–29
  75. Verdonck LF, Dekker AW, Rozenberg-Arska M, van den Hoek MR. A risk-adapted approach with a short course of ganciclovir to prevent cytomegalovirus (CMV) pneumonia in CMV-seropositive recipients of allogeneic bone marrow transplants. Clin Infect Dis. 1997;24:901–907
  76. Mori T, Okamoto S, Matsuoka S, et al.  Risk-adapted pre-emptive therapy for cytomegalovirus disease in patients undergoing allogeneic bone marrow transplantation. Bone Marrow Transplant. 2000;25:765–769
  77. Reusser P, Einsele H, Lee J, 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
  78. Mattes FM, Hainsworth E, Murdin-Geretti AM, et al.  A randomized, controlled trial comparing ganciclovir or ganciclovir plus foscarnet (each half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients. Paper presented at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy. 2001; Chicago, IL
  79. Boeckh M, Zaia JA, Jung D, Skettino S, Chauncey TR, Bowden RA. A study of the pharmacokinetics, antiviral activity, and tolerability of oral ganciclovir for CMV prophylaxis in marrow transplantation. Biol Blood Marrow Transplant. 1998;4:13–19
  80. Spielberger R, Zaia J, Nelson RA, et al.  Use of oral ganciclovir for the preventive treatment of CMV following allogeneic HCT (safety and feasibility results). Blood. 2000;96: (abstr. 586)
  81. Pescovitz MD. Oral ganciclovir and pharmacokinetics of valganciclovir in liver transplant recipients. Transpl Infect Dis. 1999;1:31–34
  82. Brown F, Banken L, Saywell K, Arum I. Pharmacokinetics of valganciclovir and ganciclovir following multiple oral dosages of valganciclovir in HIV- and CMV-seropositive volunteers. Clin Pharmacokinet. 1999;37:167–176
  83. Pescovitz MD, Rabkin J, Merion RM, et al.  Valganciclovir results in improved oral absorption of ganciclovir in liver transplant recipients. Antimicrob Agents Chemother. 2000;44:2811–2815
  84. Antin JH. Clinical practice. Long-term care after hematopoietic-cell transplantation in adults. N Engl J Med. 2002;347:36–42
  85. Ljungman P, Deliliers GL, Platzbecker U, 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
  86. Platzbecker U, Bandt D, Thiede C, et al.  Successful preemptive cidofovir treatment for CMV antigenemia after dose-reduced conditioning and allogeneic blood stem cell transplantation. Transplantation. 2001;71:880–885
  87. Chakrabarti S, Collingham KE, Osman H, Fegan CD, Milligan DW. Cidofovir as primary pre-emptive therapy for post-transplant cytomegalovirus infections. Bone Marrow Transplant. 2001;28:879–881
  88. Ljungman P, Lore K, Aschan J, et al.  Use of a semi-quantitative PCR for cytomegalovirus DNA as a basis for pre-emptive antiviral therapy in allogeneic bone marrow transplant patients. Bone Marrow Transplant. 1996;17:583–587
  89. Slavin MA, Bindra RR, Gleaves CA, Pettinger MB, Bowden RA. Ganciclovir sensitivity of cytomegalovirus at diagnosis and during treatment of cytomegalovirus pneumonia in marrow transplant recipients. Antimicrob Agents Chemother. 1993;37:1360–1363
  90. Erice A. Resistance of human cytomegalovirus to antiviral drugs. Clin Microbiol Rev. 1999;12:286–297
  91. Boivin G, Gilbert C, Gaudreau A, Greenfield I, Sudlow R, Roberts NA. Rate of emergence of cytomegalovirus (CMV) mutations in leukocytes of patients with acquired immunodeficiency syndrome who are receiving valganciclovir as induction and maintenance therapy for CMV retinitis. J Infect Dis. 2001;184:1598–1602
  92. Eckle T, Prix L, Jahn G, et al.  Drug-resistant human cytomegalovirus infection in children after allogeneic stem cell transplantation may have different clinical outcomes. Blood. 2000;96:3286–3289
  93. Eckle T, Lang P, Prix L, et al.  Rapid development of ganciclovir-resistant cytomegalovirus infection in children after allogeneic stem cell transplantation in the early phase of immune cell recovery. Bone Marrow Transplant. 2002;30:433–439
  94. Emery VC, Griffiths PD. Prediction of cytomegalovirus load and resistance patterns after antiviral chemotherapy. Proc Natl Acad Sci U S A. 2000;97:8039–8044
  95. Limaye AP, Corey L, Koelle DM, Davis CL, Boeckh M. Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants. Lancet. 2000;356:645–649
  96. Boivin G, Goyette N, Gilbert C, Roberts N, Tansley R, Covington E. Low frequency of emergence of cytomegalovirus UL97 mutations associated with ganciclovir resistance in solid organ transplant patients receiving valganciclovir or oral ganciclovir prophylaxis. Paper presented at the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy. 2002; San Diego, CA
  97. Leather HL, Meyer CL, Wingard JR. Oral valganciclovir for preemptive therapy of cytomegalovirus antigenemia in hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant. 2003;9:132; (abstr. 238)
  98. Wang LH, Peck RW, Yin Y, Allanson J, Wiggs R, Wire MB. Phase 1 safety and pharmacokinetic trials of 1263W94, a novel oral anti-human cytomegalovirus agent, in healthy and human immunodificiency virus-infected subjects. Antimicrob Agents Chemother. 2003;47:1334–1342
  99. McSharry JJ, McDonough A, Olson B, et al.  Susceptibilities of human cytomegalovirus clinical isolates to BAY38–4766, BAY43–9695, and ganciclovir. Antimicrob Agents Chemother. 2001;45:2925–2927
  100. Walter EA, Greenberg PD, Gilbert MJ, 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
  101. Peggs KS, Verfuerth S, Mackinnon S. Induction of cytomegalovirus (CMV)-specific T-cell responses using dendritic cells pulsed with CMV antigen (a novel culture system free of live CMV virions). Blood. 2001;97:994–1000
  102. Zaia JA, Sissons JG, Riddell S, et al.  Status of cytomegalovirus prevention and treatment in 2000. Hematology. 2000;339–355
  103. 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
  104. Greenberg PD, Reusser P, Goodrich JM, Riddell SR. Development of a treatment regimen for human cytomegalovirus (CMV) infection in bone marrow transplantation recipients by adoptive transfer of donor-derived CMV-specific T cell clones expanded in vitro. Ann N Y Acad Sci. 1991;636:184–195
  105. Einsele H, Roosnek E, Rufer N, 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
  106. Peggs KS, Mackinnon S. Clinical trials with CMV-specific T cells. Cytotherapy. 2002;4:21–28
  107. Hakki M, Riddell SR, Storek J, et al. Immune reconstitution to cytomegalovirus after allogeneic hematopoietic stem cell transplantation: impact of host factors, drug therapy, and subclinical reactivation. Blood. In press.

PII: S1083-8791(03)00287-8

doi: 10.1016/S1083-8791(03)00287-8

Biology of Blood and Marrow Transplantation
Volume 9, Issue 9 , Pages 543-558 , September 2003