Role of molecularly-cloned hematopoietic growth factors after acute high-dose radiation exposures
Open accessAbstract
Abstract Therapy of acute, high-dose whole-body exposures of humans to ionizing radiations is a complex medical challenge. Since 1944 more than 400 radiologic accidents have been registered with more than 3000 substantial radiation exposures and 127 fatalities. There are several potential interventions including supportive care, transfusions, preventative or therapeutic anti-infection drugs, molecularly-cloned myeloid growth factors and hematopoietic cell transplants. We discuss the use of the granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) to treat acute high-dose ionizing radiation exposures. Considerable data in experimental models including monkeys indicate use of these drugs accelerates bone marrow recovery and in some but not all instances increases survival. In ten accidents since 1996, 30 victims received G-CSF alone or with other growth factors. Twenty-six victims survived. In seven accidents since 1986, 28 victims received GM-CSF alone or with other growth factors; 18 victims survived. However, absent control or data from randomized trials, it is not possible to know with certainty what role, if any, receiving G-CSF or GM-CSF was of benefit. Given the favorable benefit-to-risk ratio of molecularly-cloned myeloid growth factors, their use soon after exposure to acute, high-dose whole-body ionizing radiations is reasonable.
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Both sargramostim and filgrastim have demonstrated a robust safety profile with well-known and minimal side effects including fever, diarrhea, bone pain, and fatigue, making them ideal for use as MCMs.
“Both drugs have demonstrated a robust safety profile with well-known and minimal side effects in patients including fever, diarrhea, bone pain, and fatigue making them ideal for use as MCMs (Lazarus and Gale, 2021).”
From Medical countermeasures for the hematopoietic-subsyndrome of acute radiation syndrome in space (2022) · cites this paper as Lazarus and Gale, 2021
Section 2 identifies filgrastim and sargramostim as FDA-approved treatments for bone marrow recovery after acute high-dose radiation exposure. Section 4 says the interventions seem safe and effective, but cautions that safety data from radiation accidents are difficult to interpret. Our copy does not identify fever, diarrhea, bone pain, or fatigue as their side effects, or establish the robust patient safety profile claimed. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMyeloid colony stimulating factors boost granulopoiesis, differentiation, maturation, and function of hematopoietic progenitor cells to accelerate recovery of blood forming cells in circulation.
“Myeloid colony stimulating factors boost granulopoiesis, differentiation, maturation, and function of hematopoietic progenitor cells to accelerate recovery of blood forming cells in circulation (Fig. 2) (Lazarus and Gale, 2021).”
From Medical countermeasures for the hematopoietic-subsyndrome of acute radiation syndrome in space (2022) · cites this paper as Lazarus and Gale, 2021
Section 2, “Molecularly-cloned myeloid growth factors” (page unavailable), identifies G-CSF and GM-CSF as factors used to accelerate bone marrow recovery after acute high-dose radiation exposure. It does not describe the claimed boosts to granulopoiesis, progenitor-cell differentiation, maturation, or function, or specifically establish faster recovery of circulating blood-forming cells. (LLM, conf=0.83)
Experimental — accuracy not yet measuredIn total, between 1996 and 2021, at least thirty patients with ARS have been treated with sargramostim and/or filgrastim.
“In total, between 1996 and 2021, at least thirty patients with ARS have been treated with sargramostim and/or filgrastim (Lazarus et al., 2021).”
From Medical countermeasures for the hematopoietic-subsyndrome of acute radiation syndrome in space (2022) · cites this paper as Lazarus et al., 2021
Section 6 reports 30 accident victims treated with G-CSF between 1996 and 2010, supporting the approximate count within the claimed period. But Table 1 lists PEGylated G-CSF for two of those victims, which Section 2 distinguishes from filgrastim; Section 6 also says exposures were acute or protracted. The paper therefore does not establish that all 30 were patients with ARS treated specifically with sargramostim and/or filgrastim. (LLM, conf=0.84)
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- Authors
- Lazarus, H. M., Armitage, J. O., & Gale, R. P.
- Affiliations
- Case Western Reserve University (US)
- University of Nebraska Medical Center (US)
- Imperial College London (GB)
- Venue
- Journal of Radiological Protection
- Publisher
- IOP Publishing
- Published
- 2021-11-10
- Volume
- 41
- Issue
- 4
- Pages
- S478-S489
- ISSN
- 0952-4746 (ISSN-L)
- 1361-6498
- OpenAlex
- W3171717947
- Cited by
- 11
- References
- 47
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2022: 3 · 2021: 2
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Radiological Protection (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Physical Sciences › Environmental Science › Global and Planetary Change › Radioactive contamination and transfer
- Keywords
- radiation accidents, granulocyte colony-stimulating factor, GM-CSF, myeloid growth factors, hematopoietic recovery, bone marrow recovery
- MeSH terms
- Radiation Exposure, Animals, Bone Marrow, Humans, Radiation, Ionizing, Granulocyte-Macrophage Colony-Stimulating Factor, Granulocyte Colony-Stimulating Factor
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