Radiation Sensitization of Leukemic Cells for Low Dose Total Body Irradiation

The treatment of pediatric leukemias has been developed through sequential clinical trials designed to improve patient survival and preserve quality of life (Brochstein et al., 1987). A patient's clinical and biological features are predictive of risk of relapse and determine the aggressiveness of the prescribed clinical treatment protocol. Patients determined to be at high risk for recurrence undergo chemotherapy and total body irradiation (TBI) in the preparative regimen for bone marrow transplantation. Such personalization of treatment has resulted in improved survival. While the 5-year overall survival of pediatric leukemia patients ranges from 60–90% (Allemani et al., 2014), children who experience bone marrow relapse have a three year event free survival of only 20%, supporting the need for further improvements (Gaynon et al., 2006). Leukemic cells are very sensitive to radiation induced apoptosis, but themagnitude of the TBI radiation dose is dictated not only by the need to control tumor cells, but also to respect normal tissue tolerances of critical organs. Dose dependent late-effects of TBI are of particular concern in the treatment of pediatric patients. In addition to acute pulmonary, cardiovascular, hepatic, and renal toxicities, treatment of children can result in endocrinopathies, neurocognitive impairment, growth disturbances, cataract formation and secondary malignancies as delayed effects (Silverman, 2014). Thus, pediatric clinical protocols focus on reducing or eliminating radiation; however, multiple clinical trials have shown that including TBI is more effective than