Hyperfractionation versus single dose irradiation in human acute lymphocytic leukemia cells: application to TBI for marrow transplantation.

Abstract

A major purpose of total body irradiation (TBI) for bone marrow transplantation in leukemia patients is to help eradicate all leukemia cells; the ideal regimen has not yet been determined. To answer basic questions regarding leukemic cell survival kinetics, a human acute lymphoblastic leukemia (ALL) cell line (Reh), with the common ALL antigen (CALLA-positive), has been used to assess in vitro the efficacy of one widely used hyperfractionated TBI (HTBI) regimen versus single dose TBI (SDTBI). The regimen studied in this model was 1.2-1.25 Gy/fraction, 3 fractions/day, 5 h apart each day, for 5 days (11-12 fractions) for a total dose of 13.2-15.0 Gy. It was found that: (i) cell survival was consistent with the linear-quadratic model for early responding tissues (alpha/beta = 7.0 Gy). (ii) The change in shape of the 'effective' cell survival curve for three fractions/day was consistent with the hypothesis that there was complete repair between fractions. (iii) Cell regrowth between fractions was minimal (< or = 5%). (iv) Division delay between fractions (2.9 h/Gy) could explain the small contribution to the survival curve of regrowth between fractions. (v) For a full HTBI course to 15 Gy, cell survival was predicted to be approximately 5 x 10(-5), compared with approximately 10(-3) for a low dose rate (0.04-0.07 Gy/min) SDTBI to 10 Gy; the latter projected from the initial slope of the high dose rate, single dose survival curve.