Human cytomegalovirus (HCMV) replication kinetics in stem cell transplant recipients following anti-HCMV therapy

J Clin Virol. 2010 Sep;49(1):32-6. doi: 10.1016/j.jcv.2010.06.018. Epub 2010 Jul 27.

Abstract

Background: Cytomegalovirus (HCMV) remains an important infection following stem cell transplantation (SCT) and is managed via pre-emptive therapy. In some patients HCMV loads continue to increase after therapy and they experience multiple episodes of replication.

Objectives: To identify the risk factors associated with failure to immediately control HCMV replication after antiviral therapy and for recurrence of replication.

Study design: Replication kinetics of human cytomegalovirus (HCMV) were studied a cohort of 153 T-cell depleted allogeneic SCT patients.

Results: In 57 patients (31%) who experienced HCMV DNAemia, the mean growth rate of HCMV was 0.35 day(-1) equivalent to a doubling time of 2.2 days. In patients requiring anti-HCMV treatment with either ganciclovir or ganciclovir/foscarnet (n=49), HCMV load increased to a peak value of >2 days after initiation of therapy in 21 patients and only the growth rate prior to therapy was a risk factor (Odds ratio=1.4 per 0.1 day(-1) increase; p=0.004). In patients where antiviral intervention occurred after peak virus load the decline rate of HCMV load was accelerated 4-fold if the patient was subsequently initiated on anti-HCMV therapy (p=0.02). A subset of patients (38%) experienced a recurrence of their DNAemia at a mean of 20 days after the cessation of their first replication episode and this was only associated with receiving stem cells from a seronegative donor (Odds ratio=6.59; p<0.001).

Conclusions: The kinetics of response to therapy is closely associated with HCMV replication kinetics prior to therapy while recurrence of replication is associated with HCMV serostatus of the donor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / therapeutic use
  • Child
  • Child, Preschool
  • Cytomegalovirus / drug effects*
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / virology
  • DNA, Viral / blood
  • Female
  • Ganciclovir / administration & dosage*
  • Ganciclovir / therapeutic use
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Risk Factors
  • Stem Cell Transplantation / adverse effects*
  • Viral Load
  • Virus Replication* / drug effects
  • Young Adult

Substances

  • Antiviral Agents
  • DNA, Viral
  • Ganciclovir