The implications ofin-vitroradiation–survival curves for the optimal scheduling of total-body irradiation with bone marrow rescue in the treatment of leukaemia

Abstract

A mathematical model for optimal scheduling of total-body irradiation (TBI) in the treatment of leukaemia is described. A survey of the radiosensitivities of human leukaemic cells indicate that they are highly radiosensitive with little fraction size dependence (median D₀ = 0.74 Gy; median D_q = 0.14Gy). These properties, when considered alongside the high repair capacity of lung, suggest that TBI schedules of the “accelerated hyperfractionation” type are optimal. The antileukaemic effects of alternative schedules, chosen to be isoeffective for lung damage to a reference schedule of 6 × 2 Gy in 3 days, were compared. A modestly hyperfractionated schedule of 10 fractions of 1.3–1.5 Gy in 5 days has theoretical advantages while retaining practicality of clinical administration.