Chemotherapy sensitivity assessment of leukemic colony-forming cells with in vitro simultaneous exposure to multiple drugs: clinical correlations in acute nonlymphocytic leukemia

Abstract

For 13 patients with acute nonlymphocytic leukemia receiving four-drug combination chemotherapy (14 chemotherapy trials), leukemic bone marrow cells were obtained before treatment and were exposed in vitro to all four-drug-mixture solutions simultaneously followed by the survival assessment of leukemic colony-forming cells (L-CFU). Survival of normal marrow colony-forming cells (CFU-C) was also assessed concurrently, and the sensitivity index (SI) of leukemic cells was determined as the ratio of the survival of CFU-C to that of L-CFU. Correlations of in vitro results to clinical results were excellent: four of five trials resulting in complete remission had high SI and eight of nine trials without complete remission had low SI (P = 0.02). The potential advantages of this method of exposing cells to drug mixture are discussed in terms of detecting drug synergism and improving the efficiency of in vitro chemotherapy sensitivity studies.