An update on sargramostim for treatment of acute radiation syndrome

The potential use by terrorists of an improvised nuclear device, a radiological dispersal device, or an unintended nuclear/radiological accident in heavily populated areas is a national security threat of major consequences. Although this type of security threat is considered to be low-risk, it would have a devastating impact. Health issues would be a major concern; medical care would be necessary for all those who received considerable radiation exposure (> 1 Gy) leading to hematopoietic acute radiation syndrome (ARS). In the past few years, the U.S. Food and Drug Administration (FDA) has approved for such radiation exposure contingencies recombinant human granulocyte colony-stimulating factor (rhG-CSF, filgrastim, Neupogen), PEGylated rhG-CSF (PEGylated filgrastim, Neulasta) and granulocyte-macrophage colony-stimulating factor (rhGM-CSF, sargramostim, Leukine) following the FDA's Animal Rule guidance. In this article, we have briefly reviewed the consequences of exposure to acute, potentially lethal doses of radiation and its pathologic sequelae, as well as ARS and the latest of the FDA-approved recombinant growth factors, namely sargramostim (Leukine), as a new treatment option for the subclinical, hematopoietic syndrome component of ARS. The nature of the recombinant and the preclinical and clinical research that preceded approval by the FDA are presented, as well as its use in the treatment of victims of radiation accidents.