Mathematical Models of Human Hematopoiesis Following Acute Radiation Exposure (original) (raw)
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Health Physics, 2010
A new model of the hematopoietic system for humans chronically exposed to ionizing radiation allows for quantitative description of the initial hematopoiesis inhibition and subsequent increase in the risks of late stochastic effects such as leukemia. This model describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the three blood cell types (leukocytes, erythrocytes, and platelets). The model parameters are estimated from the results of other experiments. They include the steady-state numbers of hematopoietic stem cells and peripheral blood cell lines for an unexposed organism, amplification parameters for each blood cell line, parameters describing the proliferation and apoptosis, parameters of feedback functions regulating the steady-state numbers, and characteristics of radiosensitivity in respect to cell death and non-lethal cell damages. The dynamic model of hematopoiesis is applied to the data on subcohort of the Techa River residents with hematological measurements (e.g., blood counts) performed in [1950][1951][1952][1953][1954][1955][1956] (which totals to about 3,500 exposed individuals). Among well-described effects observed in these data are the slope value of the dose-effect curves describing the hematopoietic inhibition and the dose rate patterns of the fractions of cytopenic states (e.g., leukopenia, thrombocytopenia). The model has been further generalized by inclusion of the component describing the risk of late stochastic effects. The risks of the development of late effects (such as leukemia) in population groups with specific patterns of early reactions in hematopoiesis (such as leukopenia induced by ionizing radiation) are investigated using simulation studies and compared to data.
International Journal of Radiation Biology, 2019
Purpose: Incidents, such as nuclear facility accidents and the release of a 'dirty bomb', might result in not only external irradiation of personnel, but additional internal exposures through concomitant inhalation and/or ingestion of radioactive particulates. The purpose of this study was to define the impact of such a combination of radiation injuries on the hematopoietic niche. Material and methods: To assess changes in the murine hematopoietic system, we used a combined exposure of total body irradiation (TBI, 6 Gy) followed immediately by an internal (intraperitoneal) administration of 100 mCi of soluble 137 Cs. We then evaluated acute survival in combined versus single modality exposure groups, as well as assessing hematopoietic function at 12 and 26 week time points. Results: Acutely, the combination of external and internal exposures led to an unexpected delay in excretion of 137 Cs, increasing the absorbed dose in the combined exposure group and leading to mortality from an acute hematopoietic syndrome. At 12 weeks, all exposure paradigms resulted in decreased numbers of phenotypic hematopoietic stem cells (HSCs), particularly the short-term HSCs (ST-HSC); long-term HSCs (LT-HSC) were depleted only in the internal and combined exposure groups. At 26 weeks, there was significant anemia in both the TBI alone and combined exposure groups. There were decreased numbers in both the LT-and ST-HSCs and decreased functionality, as measured by competitive repopulation, was seen in all radiation groups, with the greatest effects seen in the internal and combined exposure groups. Conclusions: Our data indicate that a combined injury of sublethal external irradiation with internal contamination induces significant and persistent changes in the hematopoietic system, as may have been predicted from the literature and our own group's findings. However, a novel observation was that the combined exposure led to an alteration in the excretion kinetics of the internal contamination, increasing the acute effects beyond those anticipated. As a result, we believe that a combined exposure poses a unique challenge to the medical community during both the acute and, possibly, delayed recovery stages.
Modeling the Depressed Hematopoietic Cells for Immune System under Chronic Radiation
Lecture Notes in Computer Science, 2013
Although moderate dose (0.5 to 2 Gy) of ionizing radiation (IR) is well recognized to cause various disorders of the hematopoietic system (e.g., short-term effects like cytopenia, and long-term effects like leukemia), many quantitative aspects of the dynamics of the hematopoiesis response to long duration low dose rate IR still require additional investigation. Recently two cell kinetics models after acute radiation exposure are proposed to describe the perturbation of granulocytes and lymphocytes, respectively, in peripheral blood of various mammals. These two models are indeed built on a similar coarsegrained structure of hematopoietic system, thus they have the potential to form a unified model to characterize the mammalian hematopoietic system after various types of IR exposure. In this study we investigate the capability of the models to simulate the data of hematological measurements of the Techa River residents chronically exposed to IR in 1950-1956. Our modeling investigation indicates human hematopoietic precursor cells are more sensitive to chronic radiation than previously considered.
The hematologist and radiation casualties
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program, 2003
Since the terrorist attack of September 11, 2001, preparation by the health care system for an act of terrorism has been mandated by leaders of governments. Scenarios for terrorist acts involving radioactive material have been identified, and approaches to management (based on past experience from atomic weapons detonations and radiation accidents) have been developed. Because of their experience in managing patients with profound cytopenia and/or marrow aplasia, hematologists will be asked to play a significant role in evaluating and treating victims of mass accidental or deliberate exposure to radiation. This review provides a framework for understanding how radiation levels are quantified, how radiation alters the function of hematopoietic (and nonhematopoietic) cells and tissues, and how victims receiving a significant radiation dose can be identified and managed. In Section I, Dr. Nicholas Dainiak reviews four components of the Acute Radiation Syndrome: the hematopoietic, neuro...
Military Medicine, 2002
In some radiation accidents, exposure doses are delivered over days or even months. In all cases the organ system most relevant to a patient's survival is the hematopoietic tissue. There appears to be a threshold of approximately 10 mSv per day above which hematopoietic effects become apparent and hematopoietic failure may occur. Experimental observations in dogs demonstrate that exposure to chronic v-Irradiation may be tolerated for over a year if the daily dose does not exceed 7 mSv to 18 mSv. The pathophysiological mechanisms are being studied by hematological measures and biomathematical models. The results are in accordance with the assumption of excess cell loss and progressive diminution of the stem cell pool over time until a "turbulence region," with an increased probability of system failure, is approached. Diagnostic procedures require a thorough hematological assessment that includes the stem cell compartment. Therapeutic options include administration of hematopoietic growth factors and stem cell transplantation.
Health Physics, 2010
After accidental radiation exposure, one of the most significant health impairments is the partial or complete failure of the blood forming systems. Depending on the degree of damage, a suitable therapy must be prepared in time. This requires the assessment of the degree of damage of the blood-forming system and, in particular, of the stem-cell pool. A new approach for assessing the degree of hematopoietic impairment based on dynamic reactions of blood counts immediately following radiation exposure is presented. Cell kinetic mathematical models of blood cell turnover, neural networks, and expert-assessed clinical data records of historical radiation accidents are combined to provide a method for automatic classification of patients and to assign them to clinically related categories of severity. Using this computerassisted approach, it is possible to distinguish those patients that are likely to restore their blood-cell formation autochthonously from those that need stem-cell transplantation.
Objective-Hematopoietic syndrome (HS) is a clinical diagnosis assigned to people who present with ≥1 new-onset cytopenias in the setting of acute radiation exposure. The World Health Organization convened a panel of experts to evaluate the evidence and develop recommendations for medical countermeasures for the management of HS in a hypothetical scenario involving the hospitalization of 100 to 200 individuals exposed to radiation. The objective of this consultancy was to develop recommendations for treatment of the HS based upon the quality of evidence.
Health physics, 2015
Since controlled clinical studies on drug administration for the acute radiation syndrome are lacking, clinical data of human radiation accident victims as well as experimental animal models are the main sources of information. This leads to the question of how to compare and link clinical observations collected after human radiation accidents with experimental observations in non-human primate (NHP) models. Using the example of granulocyte counts in the peripheral blood following radiation exposure, approaches for adaptation between NHP and patient databases on data comparison and transformation are introduced. As a substitute for studying the effects of administration of granulocyte-colony stimulating factor (G-CSF) in human clinical trials, the method of mathematical modeling is suggested using the example of G-CSF administration to NHP after total body irradiation.
Health Physics, 2012
AbstractVA biomathematical model of lymphopoiesis is described and used to analyze the lymphocyte changes observed in the blood of exposed victims in radiation accidents. The coarse-grained architecture of cellular replication and production and implicit cellular regulation mechanisms used in this model make it straightforward to incorporate various radiation conditions. Model simulations with reported absorbed doses as inputs are shown to qualitatively and quantitatively describe a wide range of accidental data in vastly different scenarios. In addition, the absolute lymphocyte counts and the depletion rate constants calculated by this model show good correlation with two widely recognized empirical methods for early dose assessment. This demonstrates the potential to use the biophysical model as an alternative method for the assessment of radiation injury in the case of large-scale radiation disaster. The physiological assumptions underlying the model are also discussed, which may provide a putative mechanism for some biodosimetric tools that use the peripheral blood cell counts as markers of radiation impairment. Health Phys. 102(4):425Y436; 2012