title: Treatment of adenovirus disease in stem cell transplant recipients with cidofovir.
abstract: Invasive adenovirus (AdV) disease is fatal in >50% of allogeneic hematopoietic stem cell transplant (SCT) recipients. Treatment with cidofovir may improve outcomes based on in vitro susceptibility data and case reports. Six consecutive cases of invasive AdV disease treated with cidofovir were reviewed among 84 allogeneic adult SCT recipients (incidence, 7.1%). Cidofovir was administered intravenously at 5 mg/kg per dose (1-7 doses). All patients received intravenous immune globulin. Blood AdV DNA levels (viral loads, VLs) were monitored with a real-time quantitative polymerase chain reaction assay. Published reports of cidofovir treatment of AdV disease in SCT recipients were critically reviewed. The primary manifestations of AdV disease were hepatitis (n = 3), colitis (n = 2), and nephritis (n = 1). All patients had detectable AdV VLs, with peak values from 5 x 10(5) to 2 x 10(8) copies/mL. All patients received CD34+ selected grafts (n = 3) and/or had graft-versus-host disease (n = 4) and had CD4 counts <100 cells/mm3. Only 1 of 5 patients (20%) who received >or=2 doses of cidofovir died with active AdV disease. Four patients exhibited improvement within days of treatment with cidofovir as documented by clinical criteria and declines in AdV VLs (without a change in immunosuppression). In contrast, 1 patient treated late after onset of AdV disease died after 1 dose of cidofovir. In our review of 70 published cases treated with >or=2 doses of cidofovir, 13 (19%) died from AdV disease. In conclusion, early treatment of AdV disease with cidofovir inhibits viral replication in vivo and reduces mortality in allogeneic SCT recipients compared with historical data.
authors.affiliation: Division of Infectious Diseases and Environment Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. dionissios.neofytos@mail.tju.edu
authors.forename: Dionissios
authors.initials: D
authors.lastname: Neofytos
authors.forename: Ambrish
authors.initials: A
authors.lastname: Ojha
authors.forename: Bijoyesh
authors.initials: B
authors.lastname: Mookerjee
authors.forename: John
authors.initials: J
authors.lastname: Wagner
authors.forename: Joanne
authors.initials: J
authors.lastname: Filicko
authors.forename: Andres
authors.initials: A
authors.lastname: Ferber
authors.forename: Scott
authors.initials: S
authors.lastname: Dessain
authors.forename: Dolores
authors.initials: D
authors.lastname: Grosso
authors.forename: Janet
authors.initials: J
authors.lastname: Brunner
authors.forename: Neal
authors.initials: N
authors.lastname: Flomenberg
authors.forename: Phyllis
authors.initials: P
authors.lastname: Flomenberg
mesh_terms: D000258:Adenovirus Infections, Human / Q000188:drug therapy* / Q000209:etiology; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D000077404:Cidofovir; D003092:Colitis / Q000188:drug therapy / Q000821:virology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006525:Hepatitis, Viral, Human / Q000188:drug therapy; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007155:Immunologic Factors / Q000627:therapeutic use; D008297:Male; D009393:Nephritis / Q000188:drug therapy / Q000821:virology; D063065:Organophosphonates / Q000627:therapeutic use*; D014184:Transplantation, Homologous; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir