Chemotherapeutic Sensitivity of Acute Lymphoblastic Leukemia Cells in Culture: Correlation with Clinical Efficacy on Donor Patients

The establishment of permanent acute lymphocytic leukemia (ALL) lines of different phenotypes permits the study of their sensitivity to chemotherapeutic agents. The sensitivity of four ALL cell lines, two T-cell lines and one each of B- and non-T/non-B cell lines, to eight chemotherapeutic agents was studied by means of clonogenic assay. Response data were analyzed by two criteria—one based on concentrations obtainable from the elimination phase and the other based on peak concentration—both derived from pharmacokinetic studies in man. The overall correlation between the two criteria was good and only in 5 of 32 occasions were there major discrepancies. A retrospective analysis of the clinical course of the four donor patients showed that although the one set of criteria gave a positive correlation of asparaginase response in vivo, the other positively correlated the daunorubicin response, but not vice versa. No new cut-off line could be drawn to satisfy completely in vitro/in vivo correlation for all the drugs. Although the possibility exists that a leukemic cell line may not actually be predictive of chemotherapeutic responsiveness in the donor patients, our data indicate a need to reexamine the in vitro system in predictive testing of antileukemic agents.