Prediction of in vivo cytotoxicity of chemotherapeutic agents by their in vitro effect on leukocytes from patients with acute leukemia.

SUMMARY In order to develop a test system for predicting cytotoxic response to chemotherapeutic agents, leukocytes from 36 adult patients and 2 teenagers with acute leukemia were cul tured in vitro for 24 hr and the effects of drugs on the incor poration of uridine-3H in RNA and of thymidine-'4 C in DNA were measured. Cortisol, vincristine, and cytosine arabinoside produced inhibition of uridine-3H incorporation in sensitive leukocytes. The effects of cortisol and vincristine on the incor poration of uridine-3H in RNA and of thymidine-'4 C were, in general, similar. In two studies, cytosine arabinoside produced a more profound depression of incorporation of radioactive thymidine than of radioactive uridine. From 45 in vitro and clinical studies of leukocyte response to glucorticoids and vincristine, it was concluded that the in vitro test system can predict the in vivo cytotoxicity of these compounds in acute leukemia in adults. From 8 in vitro and clinical studies of cytosine arabinoside, it appeared likely that the in vitro test system may have predictive value for the cytotoxic effect of this drug in vivo. Whereas the test system may have use in predicting in vivo cytotoxic effects, it cannot be used for predicting the likelihood of inducing a hematologic remission.