title: The impact of drug-resistant cytomegalovirus in pediatric allogeneic hematopoietic cell transplant recipients: a prospective monitoring of UL97 and UL54 gene mutations.
abstract: BACKGROUND
  Cytomegalovirus (CMV) infection is a major cause of morbidity in allogeneic hematopoietic cell transplant (alloHCT) recipients. Little is known about the epidemiology of antiviral resistance in the pediatric population. We performed the prospective study to assess the impact of drug-resistant CMV infections in pediatric alloHCT recipients.
  
  
  METHODS
  Pediatric alloHCT recipients who developed CMV infection were consecutively enrolled from May 2009 to April 2012. CMV polymerase chain reaction amplification and sequencing analysis for UL97 and UL54 genes were performed at enrollment and during follow-up.
  
  
  RESULTS
  In total, 208 sequence data from viruses in 49 recipients were eligible for the final analysis. Resistant CMV infection caused by UL97 and UL54 mutations occurred in 4.1% (2/49) and 2.0% (1/49), respectively. Known UL97 mutations, M460V and C592G, were observed in each of 2 patients. One patient with the M460V UL97 mutation had an additional T700A UL54 mutation. Drug-resistant CMV attributable mortality was 2.0% (1/49). One or more known sequence variants (drug-sensitive) were observed in all 49 patients. Thirty-one (63.3%) and 28 patients (60.9%) already had known UL97 and UL54 sequence variants before antiviral therapy, respectively.
  
  
  CONCLUSIONS
  This study provides comprehensive information on the epidemiology of both UL97 and UL54 variants and mutations in alloHCT recipients.
authors.affiliation: Center for Clinical Research, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; Graduate School of Medicine, Sungkyunkwan University, Seoul, Korea; Department of Pediatrics, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Choi
authors.forename: J-Y
authors.initials: JY
authors.lastname: Hwang
authors.forename: K-S
authors.initials: KS
authors.lastname: Park
authors.forename: Y
authors.initials: Y
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.forename: K H
authors.initials: KH
authors.lastname: Yoo
authors.forename: E-S
authors.initials: ES
authors.lastname: Kang
authors.forename: J-H
authors.initials: JH
authors.lastname: Ahn
authors.forename: K W
authors.initials: KW
authors.lastname: Sung
authors.forename: H H
authors.initials: HH
authors.lastname: Koo
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000998:Antiviral Agents / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000821:virology*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation
chemical_list: D000998:Antiviral Agents
keywords: UL54 protein; cytomegalovirus; drug resistance; ganciclovir kinase; hematopoietic stem cell transplantation