Efficacy of delayed administration of sargramostim up to 120 hours post exposure in a nonhuman primate total body radiation model.
Autor: | Zhong Y; Citoxlab, Laval, Canada., Pouliot M; Citoxlab, Laval, Canada., Downey AM; Citoxlab, Laval, Canada., Mockbee C; Partner Therapeutics, Inc, Boston, MA, USA., Roychowdhury D; Partner Therapeutics, Inc, Boston, MA, USA., Wierzbicki W; Citoxlab, Laval, Canada., Authier S; Citoxlab, Laval, Canada. |
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Jazyk: | angličtina |
Zdroj: | International journal of radiation biology [Int J Radiat Biol] 2021; Vol. 97 (sup1), pp. S100-S116. Date of Electronic Publication: 2020 Sep 22. |
DOI: | 10.1080/09553002.2019.1673499 |
Abstrakt: | Background: High dose ionizing radiation exposure is associated with myelo-depression leading to pancytopenia and the expected clinical manifestations of acute radiation syndrome (ARS). Herein, we evaluated the efficacy of sargramostim (Leukine ® , yeast-derived rhu GM-CSF), with regimens delivered at 48, 72, 96, or 120 h after radiation exposure. Methods: A randomized and blinded nonhuman primate (NHP) study was conducted to assess the effects of sargramostim treatment on ARS. NHPs were exposed to total body radiation (LD Results: Delayed sargramostim treatment at 48 h post-irradiation significantly reduced mortality ( p = .0032) and improved hematological parameters including neutrophil but also lymphocyte and platelet counts. Additional delays in sargramostim administration at 72, 96, and 120 h post-irradiation were also similarly effective at enhancing the recovery of lymphocyte, neutrophil, and platelet counts compared to control. Sargramostim treatment also improved the survival of the animals when administered at up to 96 h post-irradiation. While sargramostim treatment at 48 h significantly reduced mortality associated with sepsis ( p ≤ .01), the additional prophylactic treatment with azithromycin did not have clinically significant effects. Conclusion: In a NHP ARS model, sargramostim administered starting at 48 h post-radiation was effective to improve survival, while beneficial hematological effects were observed with sargramostim initiated up to 120 h post exposure. |
Databáze: | MEDLINE |
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