Total body irradiation prior to bone marrow transplantation; some aspects of fifty year experience.

There has been a remarkable growth in the use of bone marrow transplantation (BMT) in the past 30 years. The rapid expansion of BMT reflects its increasingly important role in the treatment of several life-threatening diseases of the hemopoietic system. The first BMT in human patients was performed after conditioning with total body irradiation (TBI). As an important part of BMT protocols, TBI has an established role in many preparative regimens used before BMT in the treatment of hematological diseases. Historically, TBI schedules varied during the last 30-year period with regard to different radiation source used, treatment technique, beam modifiers, actually delivered total dose, dose rate, and fractionation schedule. The aim of this review article is to discuss the 50- year experience in the field of TBI, as well as radiobiological, technical and dosimetric requirements and especially effects of total dose, dose rate and fractionation schedules on the prognosis of transplanted patients. The radiobiological and radio-oncological requirements demand special TBI treatment techniques quite different from usual radiotherapy. The technique needed depends extremely on the prescribed values of treatment parameters and on the local technical possibilities. TBI dosimetry has to account for the physical situation of treatment with very large field sizes at extended distances and should be performed under TBI conditions close to the real treatment situation. The effects of total dose, dose rate, fractionation schedule on the leukemia cell killing, immunosuppression, and sparing of normal tissues are considered in detail. Their effects on overall survival, leukemia recurrence, acute and chronic graft versus host disease (GvHD), late radiation-induced injuries to normal tissues or organs as well as incidence of interstitial pneumonitis, renal dysfunction and cataract development are analyzed. The definition of currently used TBI procedures is so different in different centers that retrospective analyses remain futile, under better definition and normalization of dose, fraction size, and endpoints occur. There are a lot of difficulties to evaluate, compare or understand clinical RESULTS from so different treatment regimens, often with an irregular set of parameters. In order to establish clinical trials and to evaluate clinical RESULTS, we need comparable schedules, uniform specification, and complete reporting of all relevant parameters. After 50-year experience in the field of TBI, we are beginning to understand the relationship of TBI dose, dose rate and fractionation. However, 20 years after Glasgow we will repeat his persuasion that, however, many questions remain unanswered.