Dose-dependent suppression of DNA synthesis in vitro as a predictor of clinical response in adult acute myeloblastic leukemia

Abstract

We determined for 14 patients with acute myeloblastic leukemia, prior to therapy with an anthracycline-ara-C combination, the relationship of clinical response to dose-dependent DNA synthesis inhibition produced by each agent on each patient's cultured leukemic cells. Using a microculture system ara-C and adriamycin sensitivity (D²) was determined for each patient based upon each individual's dose response curve. The 9 patients achieving complete remission and one patient who died during induction had D² values to both agents less than 7, while 4 non-responding patients had D² values in excess of 9. Correlation of D² levels with in vivo chemotherapy-induced bone marrow cytoreduction was noted for adriamycin (P < 0.005) and for ara-C (P = 0.1). A relationship between in vitro ara-C and adriamycin sensitivity (P < 0.05) suggests that they act upon similar leukemic cell populations. Inhibition of thymidine synthesis over a range of concentrations deserves further study as a rapid in vitro test for drug sensitivity in acute myeloblastic leukemia.