Prediction of effects of therapeutic total body irradiation in man.

Abstract

Total body irradiation (TBI) is an important but toxic element in the preparation of patients for bone marrow transplantation. TBI can be delivered in many different ways and analysed for many different endpoints. The published clinical and large animal experiences are reviewed to economise the search for more optimal irradiation schedules. Currently, the immunosuppressive effects and potentially lethal side effects of TBI appear to be the dominant determinants in the therapeutic ratio of TBI. Radiation survival curve parameters are estimated for bone marrow, intestines, lung and immune system in an effort to predict fractionation effects of TBI. Predictions are in reasonable agreement with retrospective clinical observations in patients and animals. High dose rate TBI, fractionated in doses greater than 2 Gy and given over 4 days or less are recommended. Further optimization attempts depend on patient's diagnosis, available bone marrow donor, lymphocyte depletion of bone marrow and prior sensitisation of recipient. Deliberate TBI dose inhomogeneities might improve the therapeutic ratio of TBI, but remain to be explored in greater detail. The proposed model for predicting TBI effects can be adapted and remain useful for future use, when more quantitative information on additional important transplant variables becomes available.