Early identification of radiation accident victims for therapy of bone marrow failure

Abstract

Ionizing radiation damages the lymphohematopoietic system via direct effects on viability and/or function of hematopoietic stem/progenitor cells and via abnormal production of cytokines (i.e., growth factors). Other tissues that have a rapid turnover (including the gastrointestinal tract and skin) are also profoundly affected by acute radiation exposure. A major issue in selection of appropriate therapy for bone marrow failure (i.e., the bone marrow syndrome) is early assessment of radiation dose. Although several biological markers are available for assessing dose received, the absolute polymorphonuclear neutrophil (PMN) and/or lymphocyte counts, together with clinical presentation (i.e., time to onset of nausea and vomiting, etc.) still provide the most practical and timely assessment of radiation dose. Limited information is available regarding CD34-positive cell frequency as a measure of radiation-induced damage to the bone marrow. Since a subpopulation of radioresistant hematopoietic stem cells may persist after exposure to high-dose radiation, the primary goal of therapy is to provide an adequate number of lymphohematopoietic stem cells for a finite (rather than indefinite) period, after which endogenous stem cells may reinstate lymphohematopoiesis. A model is presented which describes the hypothesis that stem cell clonal repopulation over time is distinct in transplant recipients who have received moderate compared to high-dose radiation exposures. Since some individuals receiving high levels of radiation and presenting with rapidly declining PMN counts spontaneously recover lymphohematopoiesis, better tools (including CD34-positive cell analysis) must be developed to select the appropriate therapy for exposed individuals.