The radiobiological basis of total body irradiation.

Total body irradiation (TBI) is an all-pervasive systemic treatment modality which is well suited to the sterilization of small numbers of widely dispersed radiosensitive cells. This makes it attractive for the treatment of leukaemia or lymphoma in remission. It is unlikely that hypoxia or repopulation will be a problem in TBI treatment of leukaemia, and clonal resistance to radiation occurs less readily than to drugs. Leukaemic cells are often radiosensitive with poor repair capacities but considerable variation is seen in laboratory studies and leukaemias may be highly individual. It is possible that programmed cell death (apoptosis) contributes to leukaemic cell killing and variability of apoptosis may give rise to biological individuality. Molecular methodologies may now be used to monitor leukaemic cell populations and may enable semi-quantitative predictive assays of radiosensitivity. When the malignant cell population is not uniformly distributed throughout the body, as in lymphoma, non-uniform TBI is appropriate, e.g. by addition of local boosts or by the combination of TBI with radiolabelled antibody treatment. Major side-effects mostly relate to critical organs with late-responding characteristics (low alpha/beta ratio, high sensitivity to fraction size or dose rate). The radiobiological basis of developmental effects in children is not well understood. In future, improved selectivity of TBI may come from molecular biological strategies to sensitize malignant cells and to protect normal tissues.