Biology of Blood and Marrow Transplantation
Volume 13, Issue 7 , Pages 765-770 , July 2007

Ganciclovir Inhibits Lymphocyte Proliferation by Impairing DNA Synthesis

  • Minoo Battiwalla

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • Corresponding Author InformationCorrespondence and reprint requests: Minoo Battiwalla, MD, Roswell Park Cancer Institute, Buffalo, NY 14202.
    • ,
  • Yiyuan Wu

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Rajinder P.S. Bajwa

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Marija Radovic

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Nikolaos G. Almyroudis

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Brahm H. Segal

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Paul K. Wallace

      Affiliations

    • Department of Pathology and Laboratory Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Ryotaro Nakamura

      Affiliations

    • Division of Hematology/Hematopoietic Cell Transplantation, City of Hope, Duarte, California
    • ,
  • Swaminathan Padmanabhan

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Theresa Hahn

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York
    • ,
  • Philip L. McCarthy Jr.

      Affiliations

    • Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York

Received 14 December 2006 ,Accepted 20 March 2007.

References 

  1. Meyers JD, Flournoy N, Thomas ED. Risk factors for cytomegalovirus infection after human marrow transplantation. J Infect Dis. 1986;153:478–488
  2. 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
  3. 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
  4. 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
  5. Bowden RA, Digel J, Reed EC, Meyers JD. Immunosuppressive effects of ganciclovir on in vitro lymphocyte responses. J Infect Dis. 1987;156:899–903
  6. 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
  7. 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
  8. 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
  9. 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
  10. Cheng YC, Huang ES, Lin JC, et al. Unique spectrum of activity of 9-[(1,3-dihydroxy-2-propoxy)methyl]-guanine against herpesviruses in vitro and its mode of action against herpes simplex virus type 1. Proc Natl Acad Sci USA. 1983;80:2767–2770
  11. Sommadossi JP, Carlisle R. Toxicity of 3′-azido-3′-deoxythymidine and 9-(1,3-dihydroxy-2-propoxymethyl)guanine for normal human hematopoietic progenitor cells in vitro. Antimicrob Agents Chemother. 1987;31:452–454
  12. Hamzeh FM, Lietman PS. Intranuclear accumulation of subgenomic noninfectious human cytomegalovirus DNA in infected cells in the presence of ganciclovir. Antimicrob Agents Chemother. 1991;35:1818–1823
  13. Reid R, Mar EC, Huang ES, Topal MD. Insertion and extension of acyclic, dideoxy, and ara nucleotides by herpesviridae, human alpha and human beta polymerases (A unique inhibition mechanism for 9-(1,3-dihydroxy-2-propoxymethyl)guanine triphosphate). J Biol Chem. 1988;263:3898–3904
  14. Freitas VR, Smee DF, Chernow M, Boehme R, Matthews TR. Activity of 9-(1,3-dihydroxy-2-propoxymethyl)guanine compared with that of acyclovir against human, monkey, and rodent cytomegaloviruses. Antimicrob Agents Chemother. 1985;28:240–245
  15. 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
  16. Crumpacker CS. Mechanism of action of foscarnet against viral polymerases. Am J Med. 1992;92:3S–7S
  17. Oberg B. Antiviral effects of phosphonoformate (PFA, foscarnet sodium). Pharmacol Ther. 1989;40:213–285
  18. Quinnan GV, Burns WH, Kirmani N, et al. HLA-restricted cytotoxic T lymphocytes are an early immune response and important defense mechanism in cytomegalovirus infections. Rev Infect Dis. 1984;6:156–163
  19. 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
  20. Gratama JW, van Esser JW, Lamers CH, et al. Tetramer-based quantification of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in T-cell-depleted stem cell grafts and after transplantation may identify patients at risk for progressive CMV infection. Blood. 2001;98:1358–1364
  21. 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;83:1971–1979
  22. Nakamura R, Battiwalla M, Solomon S, et al. Persisting posttransplantation cytomegalovirus antigenemia correlates with poor lymphocyte proliferation to cytomegalovirus antigen and predicts for increased late relapse and treatment failure. Biol Blood Marrow Transplant. 2004;10:49–57
  23. 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
  24. 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

PII: S1083-8791(07)00219-4

doi: 10.1016/j.bbmt.2007.03.009

Biology of Blood and Marrow Transplantation
Volume 13, Issue 7 , Pages 765-770 , July 2007

Article Tools

* Image Usage & Resolution