Biologically effective dose in total body irradiation and bone marrow transplantation

Bone marrow transplantation (BMT) has improved the long-term survival of patients treated for haematological malignancies. Total-body irradiation (TBI) is an important part of the conditioning regimen for BMT. Controversial results are reported whether higher TBI doses will result in a better overall and/or disease-free survival or not. The purpose of this study is to review the results of TBI treatments with different total doses, dose rates and number of fractions reported in literature and to derive dose-effect relationships for the various TBI treatment endpoints. We performed a search to identify TBI regimens and the endpoints overall survival, disease-free survival, relapse incidence and treatment-related mortality. Biologically effective doses (BEDs) were calculated using the linear-quadratic concept. For the endpoints relapse incidence, disease-free survival and overall survival we used alpha/beta =10 Gy and for the rate of sublethal damage repair a value of 1.4/h. Overall survival, disease-free survival and relapse incidence were obtained as function of the biologically effective dose. An increase in relapse-free survival and decrease of relapse incidence with larger BED values were observed. No significant relationship of overall survival with BED was observed. Normalisation of the TBI regimen (dose, dose rate and number of fractions) using the linear-quadratic concept in biologically effective dose resulted in meaningful dose-effect relationships for disease-free survival and relapse incidence