Radiobiological and Clinical Bases for Total Body Irradiation in the Leukemias and Lymphomas

Abstract

In spite of the recent introduction of conditioning regimens consisting of chemotherapy alone, therapeutic total body irradiation (TBI) remains a powerful antileukemic and immunosuppressive tool in preparative regimens for bone marrow transplantation. However, the question of the "best" TBI schedule has not been answered. Available radiobiological and clinical data show that (1) the role of fractionation (or dose rate) on leukemia cell killing may vary with the leukemia type. Acute myeloid leukemia cells have been found to be insensitive or only slightly sensitive to fractionation, whereas chronic myeloid leukemia cells appear to be sensitive. Data are still controversial for acute lymphocytic leukemia and the non-Hodgkin's lymphomas; (2) the immunosuppressive effect of TBI is very fractionation sensitive; and (3) most normal tissues at risk are also highly sensitive to fractionation and dose rate. These data permit some cautious adaptations of the TBI schemes to the type of leukemia, use of T-cell-depleted donor marrow, and potential normal tissue toxicity. However, we still lack data concerning the precise intrinsic and fractionation radiosensitivity of the leukemia/lymphoma of a given patient. Recent improvements in leukemia-cell cultures allowing the generation of dose survival curves and the study of in vitro radiation-induced apoptosis (mainly for lymphomas) may soon provide radiation oncologists with the data to allow further refinement and individualization of TBI schedules.