High rate of cytomegalovirus drug resistance among patients receiving preemptive antiviral treatment after haploidentical stem cell transplantation

J Infect Dis. 2014 Feb 15;209(4):557-61. doi: 10.1093/infdis/jit475. Epub 2013 Aug 27.

Abstract

We examined the rate, clinical impact, and risk factors of cytomegalovirus (CMV) drug resistance in 561 patients who underwent 616 hematopoietic stem cell transplantations (HSCTs) over 5 years. Drug resistance was exclusively identified in haploidentical (haplo)-HSCT recipients receiving preemptive therapy, among whom the rate was 14.5%. Resistance appeared after prolonged treatment (median, 70 days), was associated with higher preceding viral load (P < .001), and was the strongest predictor for disease by multivariate analysis. The high rate of drug resistance as interlinked with severe disease in haplo-HSCT recipients suggests the potential advantage of prophylactic over preemptive treatment in high-risk patients and highlights the need for better-tolerable anti-CMV drugs.

Keywords: antiviral drug resistance; cytomegalovirus; hematopoietic stem cell transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Antiviral Agents / administration & dosage*
  • Chi-Square Distribution
  • Child
  • Cytomegalovirus / genetics
  • Cytomegalovirus / isolation & purification*
  • Cytomegalovirus Infections / drug therapy
  • Cytomegalovirus Infections / prevention & control*
  • Cytomegalovirus Infections / virology
  • Drug Resistance, Viral
  • Female
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Prospective Studies

Substances

  • Antiviral Agents
  • Phosphotransferases (Alcohol Group Acceptor)
  • ganciclovir kinase