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- Title
Sargramostim (rhu GM-CSF) Improves Survival of Non-Human Primates with Severe Bone Marrow Suppression after Acute, High-Dose, Whole-Body Irradiation.
- Authors
Clayton, Nicholas P.; Khan-Malek, Richard C.; Dangler, Charles A.; Zhang, Donghui; Ascah, Alexis; Gains, Malcolm; Gardner, Brent; Mockbee, Colleen; Keutzer, Joan M.; McManus, John; Authier, Simon
- Abstract
Exposure to acute, high-dose, whole-body ionizing radiation results in bone marrow failure (hematopoietic acute radiation syndrome with resultant infection, bleeding, anemia, and increased risk of death). Sargramostim (yeast-derived rhu GM-CSF), a yeast-derived, molecularly cloned, hematopoietic growth factor and pleiotropic cytokine supports proliferation, differentiation, maturation and survival of cells of several myeloid lineages. We evaluated the efficacy of sargramostim in non-human primates (rhesus macaques) exposed to whole-body ionizing radiation at a 50–60% lethal dose. The primary end point was day 60 survival. Non-human primates received daily subcutaneous sargramostim (7 mcg/kg/day) or control. To reflect the anticipated setting of a nuclear or radiologic event, treatment began 48 h postirradiation, and non-human primates received only moderate supportive care (no whole blood transfusions or individualized antibiotics). Sargramostim significantly increased day 60 survival to 78% (95% confidence interval, 61–90%) vs. 42% (26–59%; P = 0.0018) in controls. Neutrophil, platelet and lymphocyte recovery rates were accelerated and infection rates decreased. Improved survival when sargramostim was started 48 h postirradiation, without use of intensive supportive care, suggests sargramostim may be effective in treating humans exposed to acute, high-dose whole-body, ionizing radiation in a scenario such as a mass casualty event.
- Subjects
MYELOSUPPRESSION; HEMATOPOIETIC growth factors; PRIMATES; HEMATOPOIESIS; IONIZING radiation; RADIATION injuries
- Publication
Radiation Research, 2021, Vol 195, Issue 2, p191
- ISSN
0033-7587
- Publication type
Article
- DOI
10.1667/RADE-20-00131.1