Page 61 - 2014 Printable Abstract Book
P. 61
submitted to Division of Allergy, Immunology and Transplantation (DAIT), National Institute of Allergy and
Infectious Diseases (NIAID) in September 2010. Neulasta was administered SC at 300 ug/kg on day 1 and
day 8 post-TBI. There was a 44% increase in survival vs the control cohort in the Neulasta-treated animals
(91% survival following Neulasta vs 48% survival in controls; P = 0.0014). This study was completed and a
final report submitted to DAIT NIAID in March 2014. The FDA convened a joint meeting of the Medical
Imaging Drugs Advisory Committee and Oncologic Drugs Advisory Committee on May 03, 2013 to discuss
the safety and efficacy of currently approved leukocyte growth factors (LGFs) as potential treatments for
radiation-induced myelosuppression associated with a radiological/nuclear incident. DAIT NIAID
submitted the Neupogen study data for the Committee’s review. Based this study and previous human
studies in the chemotherapy setting the Advisory Committee voted approval (vote 17 to 1) that Neupogen
therapy would be reasonably likely to produce a clinical benefit in humans following high dose irradiation
exposure. Licensure of LGFs for this indication has yet to be approved by the FDA. Funding provided by
NIAID Contracts #HHSN266200500043C and #HHSN272201000046C.
(S1303) Biological Dosimetry Approaches to Identify Individuals with Life-Threatening Radiation
Exposures. William F. Blakely, AFRRI, Bethesda, MD
The generic consensus approach for assessment of potential life-threatening radiation injury involves the
use of multiple parameter biological dosimetry. Diagnosis is typically based on use of clinical symptoms
and signs with use of hematology and blood chemistry changes including recent efforts involving the use
of plasma proteomic biomarkers of systematic inflammation and organ-specific injury, dosimetry
information including evidence of exposure due to the individual's time near the physical location of the
radiation source, personnel dosimeters, biophysical-based indicators of exposure (i.e., EPR measurement
of dose in fingernail clippings, etc.), measurement of radionuclides to assess potential external and
internal contamination, and dose assessment by use of cytogenetic biodosimetry. Current concepts of
operations in response to radiological mass-casualty incidents involve use of rapid triage and early use of
medical countermeasures including administration of leukocyte growth factors (LGFs) to individuals with
life-threatening acute radiation sickness (ARS). At present there is no FDA approved device approved for
biodosimetry, although the practice of the use of the dose assessment by cytogenetics (i.e., metaphase
spread dicentric and ring assay) could be considered acceptable due to its practice now for more than 60
years. Diagnostic gaps have prompted a significant emergence of research efforts to develop alternative
rapid diagnostic approaches based on a variety of technologies including gene expression changes
measured in blood (mRNA, miRNA), quantification of volatile organic compounds in breath, detection of
teeth, ocular, and skin changes using a variety of non-invasive technologies. Evidence of exposure to high-
doses (>3-7 Gy) by itself may not be sufficient to identify an individual needing early treatment with LGFs
for the bone-marrow (BM) sub-syndrome ARS due to potential confounders including partial-body
exposure and acute vs. protracted exposures. Scarce resources of available countermeasures (i.e., LGFs)
and the need for rapid diagnosis prompts a review of the utility of the various available diagnostic
technologies to trigger the initiation as well as continuation of treatment of individuals with BM ARS with
LGFs. The concept to dynamically shift from "dose" to "severity of BM-ARS risk" assessment, based on a
modification of the METROPOL's response category scoring system, during the time course of a radiation
incident will be described. [AFRRI supported this research under work unit RAB4AR. Research was also
partially supported by Inter-Agency Agreement (IAA) AFR.10.064 between AFRRI and Biomedical
59 | P a g e
Infectious Diseases (NIAID) in September 2010. Neulasta was administered SC at 300 ug/kg on day 1 and
day 8 post-TBI. There was a 44% increase in survival vs the control cohort in the Neulasta-treated animals
(91% survival following Neulasta vs 48% survival in controls; P = 0.0014). This study was completed and a
final report submitted to DAIT NIAID in March 2014. The FDA convened a joint meeting of the Medical
Imaging Drugs Advisory Committee and Oncologic Drugs Advisory Committee on May 03, 2013 to discuss
the safety and efficacy of currently approved leukocyte growth factors (LGFs) as potential treatments for
radiation-induced myelosuppression associated with a radiological/nuclear incident. DAIT NIAID
submitted the Neupogen study data for the Committee’s review. Based this study and previous human
studies in the chemotherapy setting the Advisory Committee voted approval (vote 17 to 1) that Neupogen
therapy would be reasonably likely to produce a clinical benefit in humans following high dose irradiation
exposure. Licensure of LGFs for this indication has yet to be approved by the FDA. Funding provided by
NIAID Contracts #HHSN266200500043C and #HHSN272201000046C.
(S1303) Biological Dosimetry Approaches to Identify Individuals with Life-Threatening Radiation
Exposures. William F. Blakely, AFRRI, Bethesda, MD
The generic consensus approach for assessment of potential life-threatening radiation injury involves the
use of multiple parameter biological dosimetry. Diagnosis is typically based on use of clinical symptoms
and signs with use of hematology and blood chemistry changes including recent efforts involving the use
of plasma proteomic biomarkers of systematic inflammation and organ-specific injury, dosimetry
information including evidence of exposure due to the individual's time near the physical location of the
radiation source, personnel dosimeters, biophysical-based indicators of exposure (i.e., EPR measurement
of dose in fingernail clippings, etc.), measurement of radionuclides to assess potential external and
internal contamination, and dose assessment by use of cytogenetic biodosimetry. Current concepts of
operations in response to radiological mass-casualty incidents involve use of rapid triage and early use of
medical countermeasures including administration of leukocyte growth factors (LGFs) to individuals with
life-threatening acute radiation sickness (ARS). At present there is no FDA approved device approved for
biodosimetry, although the practice of the use of the dose assessment by cytogenetics (i.e., metaphase
spread dicentric and ring assay) could be considered acceptable due to its practice now for more than 60
years. Diagnostic gaps have prompted a significant emergence of research efforts to develop alternative
rapid diagnostic approaches based on a variety of technologies including gene expression changes
measured in blood (mRNA, miRNA), quantification of volatile organic compounds in breath, detection of
teeth, ocular, and skin changes using a variety of non-invasive technologies. Evidence of exposure to high-
doses (>3-7 Gy) by itself may not be sufficient to identify an individual needing early treatment with LGFs
for the bone-marrow (BM) sub-syndrome ARS due to potential confounders including partial-body
exposure and acute vs. protracted exposures. Scarce resources of available countermeasures (i.e., LGFs)
and the need for rapid diagnosis prompts a review of the utility of the various available diagnostic
technologies to trigger the initiation as well as continuation of treatment of individuals with BM ARS with
LGFs. The concept to dynamically shift from "dose" to "severity of BM-ARS risk" assessment, based on a
modification of the METROPOL's response category scoring system, during the time course of a radiation
incident will be described. [AFRRI supported this research under work unit RAB4AR. Research was also
partially supported by Inter-Agency Agreement (IAA) AFR.10.064 between AFRRI and Biomedical
59 | P a g e
