1. Why is it important to know whole-body radiation dose?
Acute radiation syndrome (ARS) severity depends on whole-body dose and host factors, like age, immunity, etc.
Therapy for Acute Radiation Syndrome is directed at actual clinical symptoms, and clinical symptoms are anticipated (and potentially mitigated) based on estimated or actually measured whole or partial body exposure dose.
2. How to initiate therapy if all three estimates are either not available or if they give conflicting results? 5
Use highest whole-body dose estimate at outset, if dose data are conflicting
Colony stimulating factor therapy should be initiated when onset of vomiting or lymphocyte depletion kinetics suggests a whole-body exposure radiation dose for which treatment is recommended. (e.g. dose range begins at 2-3 Gy)
Therapy may be discontinued if results from chromosome dicentrics analysis indicate a lower estimate of whole-body dose.
3. What are the potential indications for the dicentric chromosome assay?
For acute event triage and management
Who may need the assay?
Victims with potential exposure dose in the range of 1.5-3 Gy, especially those exposed over a few days.
These individuals may be at risk for ARS hematological syndrome, and serial CBCs (lymphocyte kinetics) may not be as accurate in predicting dose in this range.
Those with doses higher than 1.5-3.0 Gy are probably going to be identified by serial CBCs (lymphocyte kinetics) and/or systemic signs and symptoms of ARS. This information will be available earlier.
Results from the dicentric assay may not be available for days to weeks, especially in a large mass casualty event.
Why might they need it?
Patients whose dicentric assay suggests a dose of 1-3 Gy may develop cytopenias 21-28 days after exposure.
They should be triaged close to medical facilities with expertise in hematology for follow-up during the approximate 28-day at risk period.
What is the relative value of the dicentric vs lymphocyte assay?
Dicentric assay and complete blood counts
(including lymphocyte kinetics may both be useful in decision-making, although blood count results will be the primary source of management information because results will be available sooner.
Chromosomal dicentric count is the current "gold standard" for biodosimetry.
Dose-related effects of radiation damage are seen if the blood sample for chromosome analysis is drawn at least 24 hours after the exposure, but useful information can be probably be obtained if the blood is drawn within a few weeks. As few as 20 metaphases may be scored to provide a preliminary estimate of dose, although scoring 50 is probably better.
Scoring should be increased to 50 cells where there is disagreement with the initial assessments or evidence of significantly inhomogeneous exposure.
For risk assessment for carcinogenicity
Although there are currently no known effective interventions to prevent cancer, an exposure-based risk assessment may be useful in directing follow-up.
Patients whose dicentric assay suggests an exposure dose between 0.25-1 Gy are unlikely to develop significant ARS, but may need long term follow-up for a low but measurable risk of radiation-related carcinogenic events.
Patients whose exposure dose is estimated to have been <0.25 Gy have a very low additional lifetime risk of cancer from radiation exposure. Special follow-up based on radiation exposure is not recommended for these individuals.
The dicentric assay may be useful for evaluating the large number of individuals who were received some exposure, perhaps > 1 Gy. Results can provide information about potential future risk and help generate guidance about monitoring and follow-up.
Initiate treatment with granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor in victims who develop an absolute neutrophil count < 0.500 x 109 cells/L and are not already receiving colony-stimulating factor.
Consider initiating therapy at lower whole body exposure dose in nonadolescent children and elderly persons because their marrow reserve may be compromised.
Bauchinger M, Blakely WF, Darroudi F, Edwards A, Fenech M, Hayata I, Koteles GJ, Lindholm C, Lloyd D, Lucas J, Prasanna PGS, Roy L, Sorokine-Durm I, Turai I, Voisin P: Cytogenetic Analysis for Radiation Dose Assessment: A Manual. (PDF - 859 KB) IAEA Technical Report Series No. 405, pp.127, Vienna, 2001
Dainiak N, Waselenko JK, Armitage JO, MacVittie TJ, Farese AM. The hematologist and radiation casualties. Hematology Am Soc Hematol Educ Program. 2003;:473-96. [PubMed Citation]
