Related Experiment Video
Updated: Dec 20, 2025
Induction of Graft-versus-host Disease and In Vivo T Cell Monitoring Using an MHC-matched Murine Model
Published on: August 29, 2012
Quantification of Radiation Injury on Neutropenia and the Link between Absolute Neutrophil Count Time Course and
John Harrold1,2, Per Olsson Gisleskog3,4, Isabelle Delor3
1Department of Clinical Pharmacology, Modeling and Simulation, Amgen Inc., Thousand Oaks, California, USA.
Purpose:
To model absolute neutrophil count (ANC) suppression in response to acute radiation (AR) exposure and evaluate ANC time course as a predictor of overall survival (OS) in response to AR exposure with or without treatment with granulocyte colony-stimulating factor in nonhuman primates.
Methods:
Source data were obtained from two pivotal studies conducted in rhesus macaques exposed to 750 cGy of whole body irradiation on day 0 that received either placebo, daily filgrastim, or pegfilgrastim (days 1 and 8 after irradiation). Animals were observed for 60 days with ANC measured every 1 to 2 days. The population model of ANC response to AR and the link between observed ANC time course and OS consisted of three submodels characterizing injury due to radiation, granulopoiesis, and a time-to-event model of OS.
Results:
The ANC response model accurately described the effects of AR exposure on the duration of neutropenia. ANC was a valid surrogate for survival because it explained 76% (95% CI, 41%-97%) and 73.2% (95% CI, 38.7%-99.9%) of the treatment effect for filgrastim and pegfilgrastim, respectively.
Conclusion:
The current model linking radiation injury to neutropenia and ANC time course to OS can be used as a basis for translating these effects to humans.
