title: Filgrastim improves survival in lethally irradiated nonhuman primates.
abstract: Treatment of individuals exposed to potentially lethal doses of radiation is of paramount concern to health professionals and government agencies. We evaluated the efficacy of filgrastim to increase survival of nonhuman primates (NHP) exposed to an approximate mid-lethal dose (LD(50/60)) (7.50 Gy) of LINAC-derived photon radiation. Prior to total-body irradiation (TBI), nonhuman primates were randomized to either a control (n = 22) or filgrastim-treated (n = 24) cohorts. Filgrastim (10 μg/kg/d) was administered beginning 1 day after TBI and continued daily until the absolute neutrophil count (ANC) was >1,000/μL for 3 consecutive days. All nonhuman primates received medical management as per protocol. The primary end point was all cause overall mortality over the 60 day in-life study. Secondary end points included mean survival time of decedents and all hematologic-related parameters. Filgrastim significantly (P < 0.004) reduced 60 day overall mortality [20.8% (5/24)] compared to the controls [59.1% (13/22)]. Filgrastim significantly decreased the duration of neutropenia, but did not affect the absolute neutrophil count nadir. Febrile neutropenia (ANC <500/μL and body temperature ≥ 103°F) was experienced by 90.9% (20/22) of controls compared to 79.2% (19/24) of filgrastim-treated animals (P = 0.418). Survival was significantly increased by 38.3% over controls. Filgrastim, administered at this dose and schedule, effectively mitigated the lethality of the hematopoietic subsyndrome of the acute radiation syndrome.
authors.affiliation: Department of Radiation Oncology, University of Maryland, School of Medicine, Baltimore, Maryland, USA. afarese@som.umaryland.edu
authors.forename: Ann M
authors.initials: AM
authors.lastname: Farese
authors.forename: Melanie V
authors.initials: MV
authors.lastname: Cohen
authors.forename: Barry P
authors.initials: BP
authors.lastname: Katz
authors.forename: Cassandra P
authors.initials: CP
authors.lastname: Smith
authors.forename: Allison
authors.initials: A
authors.lastname: Gibbs
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Cohen
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: MacVittie
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000528:radiation effects; D001803:Blood Transfusion; D003967:Diarrhea / Q000188:drug therapy; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008253:Macaca mulatta; D008297:Male; D009503:Neutropenia / Q000382:microbiology; D009504:Neutrophils / Q000187:drug effects / Q000528:radiation effects; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D000900:Anti-Bacterial Agents; D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim