title: [Ganciclovir treatment failure in adult allogeneic hematopoietic stem cell transplant recipients with cytomegalovirus infection--a single centre experience].
abstract: OBJECTIVE
  To determine the incidence of infection with ganciclovir-resistant cytomegalovirus (CMV) in adult allogeneic hematopoietic stem cell transplant (HSCT) recipients. Clinical resistance or treatment failure was defined as persistent DNAemia or increasing viral load in peripheral blood after 2 weeks of virostatic treatment. The association between the treatment failure and viral resistance was analysed. The presence of ganciclovir-resistant CMV strains was confirmed by genotypic testing able to detect mutations conferring resistance.
  
  
  METHODS
  In 2012 and 2014, 40 patients who underwent allogeneic HSCT for hematologic malignancies and were treated for human CMV reactivation/disease were followed up prospectively. In patients with treatment failure, CMV DNA was isolated and analysed by nucleotide sequence analysis of the UL 97 and UL 54 genes conferring resistance to the virostatic agent.
  
  
  RESULTS
  The treatment failure occurred in seven patients, but ganciclovir resistance conferring mutations were only detected in two of them (mutations L595F and M460I in the UL 97 gene). Another mutation in the UL 97 gene (N510S) was found in a patient with recurrent CMV replication who needed to be retreated but did not meet the criteria for treatment failure.
  
  
  CONCLUSIONS
  The low incidence of genetically confirmed ganciclovir-resistant CMV isolates in HSCT recipients with relatively common clinical treatment failure suggests that the mechanism underlying slower viral clearance is often other than mutations conferring ganciclovir resistance to the virus.
authors.forename: E
authors.initials: E
authors.lastname: Vejražková
authors.forename: P
authors.initials: P
authors.lastname: Hubáček
authors.forename: R
authors.initials: R
authors.lastname: Kutová
authors.forename: L
authors.initials: L
authors.lastname: Plíšková
authors.forename: M
authors.initials: M
authors.lastname: Košťál
authors.forename: V
authors.initials: V
authors.lastname: Štěpánová
authors.forename: A
authors.initials: A
authors.lastname: Zavřelová
authors.forename: J
authors.initials: J
authors.lastname: Radocha
authors.forename: E
authors.initials: E
authors.lastname: Malá
authors.forename: P
authors.initials: P
authors.lastname: Žák
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000188:drug therapy* / Q000209:etiology / Q000821:virology; D024882:Drug Resistance, Viral; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011183:Postoperative Complications / Q000188:drug therapy* / Q000209:etiology / Q000821:virology; D014184:Transplantation, Homologous / Q000009:adverse effects*; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D015774:Ganciclovir