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The influence of total dose, fractionation, dose rate, and distribution of total body irradiation on bone marrow transplantation.

Total body irradiation (TBI) is a common component of many preparative regimens used prior to bone marrow transplantation. The biologic effects of TBI are influenced by a number of factors, including total dose, dose fractionation, dose rate, and dose distribution. Higher doses of TBI result in greater antileukemic activity, but this effect may be offset by concomitant increases in treatment-related toxicities. Increased doses of TBI also produce a greater degree of immunosuppression. Fractionated TBI results in decreased late toxicities and immunosuppressive effects when compared with single-dose TBI, yet the extent of marrow ablation seems to be similar. For both single-dose and fractionated TBI, higher dose rates produce increased treatment-related toxicities. Dose rates also may affect marrow ablation and immunosuppression. By targeting radiation to leukemic or immunocompetent cells, alterations in dose distribution have the potential to significantly improve the clinical benefits of TBI. Directed external beam irradiation is one approach to achieving the goal of targeted therapy. Other approaches involve the conjugation of radionuclides to antibodies that recognize specific cell-surface antigens or to aminophosphonic acid compounds that bind to bone. Such specific targeting of radiation could lead to significant increases in the intensity of therapy without resulting in greater treatment-related toxicities.