RADIOSENSITIVITY OF HUMAN CLONOGENIC MYELOMA CELLS AND NORMAL BONE-MARROW PRECURSORS - EFFECT OF DIFFERENT DOSE-RATES AND FRACTIONATION

Purpose: Evaluation of radiation dose rate and fractionation effects o n clonogenic myeloma cells. Methods and Materials: The radiosensitivit y of clonogenic myeloma cells was evaluated for seven human myeloma ce ll lines. The lines were maintained in liquid suspension culture. Foll owing radiation, cells were plated in semisolid medium using methylcel lulose as viscous support. Radiation doses up to 12 Gy were delivered at dose rates of 0.05 and 0.5 Gy/min by a Co-60 source. Each total dos e was administered either as a single dose or in multiple fractions of 2 Gy. The data were analyzed according to the linear quadratic and mu lti target model of irradiation. Results: Clonogenic progenitors of th e seven myeloma cell lines differed in their radiosensitivity as measu red by multiple parameters. The differences were mainly observed at lo w dose. The most effective cytoreduction was seen when radiation was a dministered in a single fraction at high dose rate. The cytoreductive effect on clonogenic myeloma cells was compared for clinically practic ed total body irradiation (TBI) schedules delivered either in a single or in multiple fractions without causing significant pulmonary toxici ty. The administration of 12 Gy delivered in six fractions of 2 Gy res ulted in a superior reduction of clonogenic cells compared to a single fraction of 5 Gy. Conclusion: The preparation of bone marrow transpla nt recipients with multiple myeloma using fractionated radiation with a total dose of 12 Gy appears to afford better ablation than a single dose of 5 Gy while maintaining a low incidence of pulmonary toxicity.