Validation of biological dosimetry versus physical dosimetry in conditioned patients using total body irradiation: cytogenetic and FISH study

Purpose. - Validation of biological dosimetry versus physical dosimetry in malignant hemopathy patients conditioned by total body irradiation (TBI) before bone marrow transplantation (BMT). Patients and methods. -The scoring of chromosomal aberrations in peripheral lymphocytes irradiated in vivo was used to perform the biological dosimetry. The data were compared to those obtained with healthy volunteers' total blood exposed to in vitro irradiation with linear accelerator doses (0.2, 0.5, 0.75, 1, 2, 3, 4 and 5 Gy) for dose-response curves. In experimental animal models, can in vivo and in vitro responses be considered as being the same? All the published human data are based on retrospective dose evaluation with very large uncertainties on the dose precisely delivered to the subject. TBI before BMT was taken as a model where the dose calculation results from the physical method, with homogeneous beam and dose delivered precisely along the entire organism. In vivo response allows us to validate biological dosimetry in 15 adult patients (female + male), before (D = 0 Gy) and after the first fraction of 1.8 Gy, delivered by a linear accelerator (18 MV, dose-rate of 15.8 cGy/min-1). Two methods, conventional cyto-genetics (CCG) and fluorescent in situ hybridization (FISH painting) of chromosome 4 were respectively used to analyze the unstable chromosome aberrations and stable chromosome aberrations. Results. -Healthy volunteer lymphocytes, before irradiation, yielded 0.1 % dicentrics and 0.3% translocations of chromosome 4, with 2.5% for the whole genome. Patients before irradiation had 2% dicentrics and 11.48% chromosome 4 translocations for the whole genome. In the 15 patients, for a physical dose of 1.8 Gy, the evaluated biological dose was 1.93 Gy (95% CI: 1.85-2.05 Gy) with conventional cyto-genetics and 2.06 Gy (95% CI: 1.75-2.15 Gy) with FISH. Conclusion. - These results, in which the biologically estimated dose is in complete agreement with the dose calculated by physical dosimetry in the homogeneous irradiation model, suggest the validation of biological dosimetry in TBI conditioning. (authors)