title: Valganciclovir for the prevention of complications of late cytomegalovirus infection after allogeneic hematopoietic cell transplantation: a randomized trial.
abstract: BACKGROUND
  Optimal prevention of late cytomegalovirus (CMV) disease is poorly defined.
  
  
  OBJECTIVE
  To compare valganciclovir prophylaxis with polymerase chain reaction-guided preemptive therapy.
  
  
  METHODS
  Randomized, double-blind trial. (ClinicalTrials.gov: NCT00016068).
  
  
  METHODS
  Multicenter trial.
  
  
  METHODS
  184 recipients of hematopoietic cell transplantation (HCT) who were at high risk for late CMV disease (95 patients received valganciclovir and 89 received placebo).
  
  
  METHODS
  6 months of valganciclovir (900 mg/d) or placebo. Patients with polymerase chain reaction positivity at 1000 copies/mL or greater or a 5-fold increase over baseline were treated with ganciclovir or valganciclovir (5 mg/kg or 900 mg twice daily, respectively).
  
  
  METHODS
  The composite primary end point was death, CMV disease, or other invasive infections by 270 days after HCT. Secondary end points were CMV disease, CMV DNAemia, death, other infections, resource utilization, ganciclovir resistance, quality of life, immune reconstitution, and safety.
  
  
  RESULTS
  The primary composite outcome occurred in 20% of valganciclovir recipients versus 21% of placebo-preemptive therapy recipients (treatment difference, -0.01 [95% CI, -0.13 to 0.10]; P = 0.86). There was no difference in the primary end point or its components 640 days after HCT. The incidence of a CMV DNAemia level of 1000 copies/mL or greater or a 5-fold increase over baseline was reduced in the valganciclovir group (11% vs. 36%; P < 0.001). Neutropenia was not significantly different at the absolute neutrophil count of less than 0.5 × 109 cells/L (P = 0.57); however, more patients received hematopoietic growth factors in the valganciclovir group (25.3% vs. 12.4%; P = 0.026). No significant differences were seen in other secondary outcomes.
  
  
  CONCLUSIONS
  Some high-risk patients were not included.
  
  
  CONCLUSIONS
  Valganciclovir prophylaxis was not superior in reducing the composite end point of CMV disease, invasive bacterial or fungal disease, or death when compared with polymerase chain reaction-guided preemptive therapy. Both strategies performed similarly with regard to most clinical outcomes.
  
  
  BACKGROUND
  Roche Laboratories.
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
authors.forename: W Garrett
authors.initials: WG
authors.lastname: Nichols
authors.forename: Roy F
authors.initials: RF
authors.lastname: Chemaly
authors.forename: Genovefa A
authors.initials: GA
authors.lastname: Papanicolaou
authors.forename: John R
authors.initials: JR
authors.lastname: Wingard
authors.forename: Hu
authors.initials: H
authors.lastname: Xie
authors.forename: Karen L
authors.initials: KL
authors.lastname: Syrjala
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
authors.forename: Terry
authors.initials: T
authors.lastname: Stevens-Ayers
authors.forename: Keith R
authors.initials: KR
authors.lastname: Jerome
authors.forename: Wendy
authors.initials: W
authors.lastname: Leisenring
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000517:prevention & control*; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D015774:Ganciclovir / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D016133:Polymerase Chain Reaction; D011788:Quality of Life; D016896:Treatment Outcome; D000077562:Valganciclovir; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D000077562:Valganciclovir; D015774:Ganciclovir