Global Rare Diseases, Sanofi Genzyme, Cambridge, Massachusetts.
Global Biostatistics and Programming, Sanofi, Bridgewater, New Jersey.
Radiat Res. 2021 Feb 1;195(2):191-199. doi: 10.1667/RADE-20-00131.1.
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.
急性、高剂量、全身电离辐射暴露会导致骨髓衰竭（伴有感染、出血、贫血和死亡风险增加的造血急性辐射综合征）。沙格司亭（酵母来源的 rhu GM-CSF）是一种酵母来源的、分子克隆的、造血生长因子和多效细胞因子，支持多种髓系细胞的增殖、分化、成熟和存活。我们评估了沙格司亭在接受全身电离辐射（50-60%致死剂量）的非人类灵长类动物（恒河猴）中的疗效。主要终点是第 60 天的存活率。非人类灵长类动物每天接受皮下沙格司亭（7 mcg/kg/天）或对照治疗。为反映核或放射事件的预期情况，治疗在照射后 48 小时开始，非人类灵长类动物仅接受适度的支持性护理（不进行全血输注或个体化使用抗生素）。沙格司亭显著提高了第 60 天的存活率，达到 78%（95%置信区间，61-90%），而对照组为 42%（26-59%；P=0.0018）。中性粒细胞、血小板和淋巴细胞的恢复速度加快，感染率降低。在开始照射后 48 小时开始使用沙格司亭，无需进行强化支持性护理，就可以提高存活率，这表明沙格司亭可能对治疗在大规模伤亡事件等情况下暴露于急性、高剂量全身电离辐射的人类有效。
