title: Cidofovir for the treatment of adenoviral infection in pediatric hematopoietic stem cell transplant patients.
abstract: BACKGROUND
  Adenovirus (ADV) infections are associated with significant morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The virus is endemic in the general pediatric population and frequently causes severe disease in immunocompromised patients, especially children. We report our experience with cidofovir (CDV) for treatment of ADV infection in 57 HSCT patients, median age 8 years (range 0.5-26).
  
  
  METHODS
  Peripheral blood was prospectively screened weekly on all patients for ADV by quantitative real-time PCR for the first 100 days post-HSCT or longer if clinically indicated. Cultures for viral pathogens were performed from other involved sites. Upon detection of ADV by PCR, culture or tissue histopathology, CDV was given intravenously at 5 mg/kg weekly for 2 consecutive weeks, then every 2 weeks until 3 consecutive ADV-negative samples were documented from all previously invoved sites.
  
  
  RESULTS
  The clinical manifestations of ADV infection were: diarrhea (53%), fever (21%), hemorrhagic cystitis (12%), and pneumonitis (11%). Eight patients (14%) presented with disseminated disease. CDV treatment resulted in complete resolution of clinical symptoms in 56 (98%) patients in whom the virus became undetectable by all methods. One patient died due to ADV pneumonitis. No cases of dose-limiting nephrotoxicity were observed. CONCLUSIONS. Cidofovir appeared safe and effective for the treatment of ADV infection in this predominantly pediatric HSCT population. Vigilant surveillance and early treatment with CDV can prevent the poor outcomes associated with ADV disease. A larger prospective study is needed to further determine the role of CDV in the treatment of ADV after HSCT.
authors.affiliation: Division of Stem Cell Transplantation, Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. usman.yusuf@stjude.org
authors.forename: Usman
authors.initials: U
authors.lastname: Yusuf
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hale
authors.forename: Jeanne
authors.initials: J
authors.lastname: Carr
authors.forename: Zhengming
authors.initials: Z
authors.lastname: Gu
authors.forename: Ely
authors.initials: E
authors.lastname: Benaim
authors.forename: Paul
authors.initials: P
authors.lastname: Woodard
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kasow
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Horwitz
authors.forename: Wing
authors.initials: W
authors.lastname: Leung
authors.forename: Deo Kumar
authors.initials: DK
authors.lastname: Srivastava
authors.forename: Rupert
authors.initials: R
authors.lastname: Handgretinger
authors.forename: Randall T
authors.initials: RT
authors.lastname: Hayden
mesh_terms: D000256:Adenoviridae / Q000302:isolation & purification; D000258:Adenovirus Infections, Human / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D008297:Male; D063065:Organophosphonates / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir