Cytokine use in the hematopoietic subsyndrome of acute radiation syndrome (H-ARS): implications for the role of cytokines in a mass casualty radiologic/nuclear (R/N) emergency

A World Health Organisation panel previously recommended the use of hematopoietic cytokines to manage H-ARS within 24 h of exposure to ⩾2 Gy radiation dose, a recommendation that has been endorsed by hematologists and oncologists with expertise in radiation management. Nevertheless, no state-of-the-art consensus has been reached regarding categorical selection of cytokines for emergency scenarios involving accidental exposures where implementation of planned and/or extended countermeasures is certain or likely (International Nuclear and Radiological Event Scale levels 5, 6 and 7) or an exposure from a detonated nuclear weapon. A systematic review of the published literature was conducted (422 citations identified, 391 of which were screened) in non-human primates 9 meeting inclusion criteria), and in reviews of human cases treated with cytokines in a search of the MEDLINE database (1970-present), websites/official publications of major national and international organisations and radiation societies, cytokine reviews and full prescribing information. In contrast to filgrastim, pegfilgrastim and romiplostim, sargramostim augments the differentiation and proliferation of multiple lymphohematopoietic lineages. NHP survival benefits without the support of blood products was reported with sargramostim or pegfilgrastim plus romiplostim. Four cytokine reviews met criteria for summarising published reports of 63 human cases that included at least one case meeting inclusion criteria. Cytokine efficacy was documented when administered at up to 96 h after NHP exposure for sargramostim and at 24 h but not 48 h after exposure for filgrastim, pegfilgrstim or pegfilgrastim plus romiplostim. Ease of use favoured pegfilgrastim (administered weekly x2) and romiplostim (administered once), compared to filgrastim and sargramostim (administered daily x5 and x14, respectively). Formal assessment of the published evidence is urgently needed to provide categorical guidance regarding cytokine use for patient management, and to public health officials involved in establishing a national or shared regional radiation stockpile for immediate use in a mass casualty radiological/nuclear (R/N) emergency.