Neulasta regimen for the hematopoietic acute radiation syndrome: effects beyond neutrophil recovery
Abstract
Purpose Understanding the physiopathology underlying the acute radiation syndrome (ARS) and the mechanism of action of drugs known to ameliorate ARS is expected to help identify novel countermeasure candidates and improve the outcome for victims exposed to radiation. Granulocyte colony-stimulating factor (G-CSF) has been approved by the US Food and Drug Administration for treatment of hematopoietic ARS (H-ARS) because of its ability to alleviate myelosuppression. Besides its role in hematopoiesis, G-CSF is known to protect the cardiovascular and neurologic systems, to attenuate vascular injury and cardiac toxicity, to preserve gap junction function, and to modulate inflammation and oxidative stress. Here, we characterized the protective effects of G-CSF beyond neutrophil recovery in minipigs exposed to H-ARS doses. Methods and materials Twenty male Göttingen minipigs were exposed to total body, acute ionizing radiation. Animals received either pegylated G-CSF (Neulasta) or dextrose at days 1 and 8 after irradiation. Survival was monitored over a 45-day period. Results Neulasta decreased mortality compared with the control, reduced nadir and duration of neutropenia, and lowered prevalence of organ hemorrhage and frank bleeding episodes. Neulasta also increased plasma concentration of IGF-1 hormone, activated the cardiovascular protective IGF-1R/PI3K/Akt/eNOS/NO pathway, and enhanced membrane expression of VE-cadherin in the heart, improving vascular tone and barrier function.…
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In addition to clinical experience in radiological accident victims, there is a wealth of literature evaluating the efficacy of colony stimulating factors in well-controlled, randomized studies in canine, swine, and non-human primate models.
“However, in addition to clinical experience in radiological accident victims, there is a wealth of literature evaluating the efficacy of colony stimulating factors in wellcontrolled, randomized studies in canine, swine, and non-human primate models (MacVittie et al., 1991;Moroni et al., 2013;Legesse et al., 2019).”
From Medical countermeasures for the hematopoietic-subsyndrome of acute radiation syndrome in space (2022) · cites this paper as Legesse et al., 2019
Those studies provide strong evidence for an acceleration of recovery from myelosuppression with a reduced risk for infection and bleeding leading to an improvement in the likelihood of survival.
“In total, those studies provide strong evidence for an acceleration of recovery from myelosuppression with a reduced risk for infection and bleeding leading to an improvement in the likelihood of survival.”
From Medical countermeasures for the hematopoietic-subsyndrome of acute radiation syndrome in space (2022) · cites this paper as Legesse et al., 2019
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References 66 · Cited by 20
- Authors
- Legesse, B., Kaur, A., Kenchegowda, D., Hritzo, B., Culp, W. E., & Moroni, M.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- Corresponding author
- Moroni, Maria
- Venue
- International Journal of Radiation Oncology*Biology*Physics
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 103
- Issue
- 4
- Pages
- 935-944
- ISSN
- 0360-3016 (ISSN-L)
- OpenAlex
- W2902613231
- Cited by
- 20
- References
- 66
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 1
- FWCI
- 1.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Radiation Oncology*Biology*Physics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Health Sciences › Medicine › Oncology › Neutropenia and Cancer Infections
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- hematopoietic acute radiation syndrome, pegfilgrastim, pegylated G-CSF, granulocyte colony-stimulating factor, radiation countermeasures, minipigs, neutropenia, insulin-like growth factor I, VE-cadherin, endothelial barrier function, NADPH oxidase, oxidative stress, C-reactive protein, myelosuppression, survival
- MeSH terms
- Filgrastim, Animals, C-Reactive Protein, Endothelium, Insulin-Like Growth Factor I, Male, Neutrophils, Polyethylene Glycols, Swine, Signal Transduction, Survival Analysis, Oxidative Stress, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Nitric Oxide Synthase Type III, Acute Radiation Syndrome
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