Ganciclovir Inhibits Lymphocyte Proliferation by Impairing DNA Synthesis

Minoo Battiwalla, Yiyuan Wu, Rajinder P.S. Bajwa, Marija Radovic, Nikolaos G. Almyroudis, Brahm H. Segal, Paul K. Wallace, Ryotaro Nakamura, Swaminathan Padmanabhan, Theresa Hahn, Philip L. McCarthy

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Cytomegalovirus (CMV) disease-related mortality in allogeneic hematopoietic stem cell transplant (HSCT) recipients has dramatically declined because of ganciclovir prophylaxis and preemptive therapeutic strategies. However, ganciclovir has not improved overall survival in randomized studies despite effectively preventing overt CMV disease. Moreover, recurrent posttransplant CMV antigenemia, associated with prolonged ganciclovir exposure, is a predictor of increased relapse of malignancy. We examined the hypothesis that ganciclovir itself may have a negative impact on immune reconstitution by testing the effect of ganciclovir on normal human lymphocytes in vitro. T-lymphocyte activation and proliferation, as measured by PHA-induced 3H-thymidine uptake, was greatly reduced at therapeutic concentrations of ganciclovir (10 μg/mL) but not for foscarnet (300 μM/L). Moreover, ganciclovir impaired bromodeoxyuridine incorporation in proliferating lymphocytes, but did not impair lymphocyte survival or induce lymphocyte apoptosis. Collectively, these results show that ganciclovir suppresses T-lymphocyte proliferation in vitro by inhibiting DNA synthesis; with implications for T-lymphocyte function following allogeneic BMT.

Original languageEnglish (US)
Pages (from-to)765-770
Number of pages6
JournalBiology of Blood and Marrow Transplantation
Volume13
Issue number7
DOIs
StatePublished - Jul 2007

Keywords

  • CMV
  • DNA polymerase
  • Ganciclovir

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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