Late effects of total body irradiation

Total body irradiation (TBI) is a powerful but potentially hazardous tool used in the eradication of malignant cells and the suppression of the immune system to enable bone marrow engraftment. The occasion of its use is confined to bone marrow transplantation (BMT) in malignant disorders and some non-malignant haematological and metabolic conditions and is accompanied by high dose chemotherapy. Since infection and graft versus host disease (GVHD) may also complicate BMT untangling factors leading to late sequelae may be a difficult task and frequently there is more than one cause of any single pathological event. The radiation dose employed in TBI is as high above the median lethal dose (LD50) for 'marrow death' as possible before encountering significant bowel or lung toxicity. Most early experience was gained with single fraction TBI and doses ofup to a 10 Gy proved effective and safe; if fast dose rates were used the acute toxicity increased unless the total dose was lowered. Latterly and as in virtually all other clinical radiotherapy the benefits of fractionation have been realised. By dividing the TBI dose in several fractions over a number of days the acute toxicity is lowered, the total TBI dose may be safely raised (for example 12-15 Gy in six fractions), and dose rate is less important.' Of great significance is the fact that the higher total dose achieved by fractionation probably allows greater leukaemic cell kill and the lower doses per fraction reduce the late normal tissue morbidity. This forms the basis for this review which will focus on late sequelae ofTBI usually presenting a year or more from exposure. They can be grouped into late effects pertaining to growth and the endocrine system, specific organs, and second malignancy.