Filgrastim improves survival in lethally irradiated nonhuman primates

Ann M. Farese, Melanie V. Cohen, Barry P. Katz, Cassandra P. Smith, Allison Gibbs, Daniel M. Cohen, Thomas J. MacVittie

Research output: Contribution to journalArticle

89 Scopus citations

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 (LD50/60) (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.

Original languageEnglish (US)
Pages (from-to)89-100
Number of pages12
JournalRadiation research
Volume179
Issue number1
DOIs
StatePublished - Jan 2013

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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    Farese, A. M., Cohen, M. V., Katz, B. P., Smith, C. P., Gibbs, A., Cohen, D. M., & MacVittie, T. J. (2013). Filgrastim improves survival in lethally irradiated nonhuman primates. Radiation research, 179(1), 89-100. https://doi.org/10.1667/RR3049.1