Antagonistic effect of doxorubicin and VCR on primary leukemic tumor cells. (A) Three primary leukemia samples (patients 6, 10, and 12 from panel C) were simultaneously stimulated with doxorubicin (300 ng/mL) and VCR (300 ng/mL). Apoptosis induction was measured after 48 hours, when spontaneous apoptosis had reached 40%, otherwise after 72 hours. (B) Patient sample 10 (left panel, VCR 300 ng/mL) and patient 6 (right panel, VCR 30 ng/mL) from panel A were stimulated with doxorubicin and VCR (as indicated). (C) Thirty-five primary leukemia samples were stimulated with either doxorubicin or VCR alone or simultaneously with doxorubicin and VCR as in panel A. All samples were sensitive for doxorubicin (specific apoptosis > 10%) besides samples 29 to 32. Measured apoptosis for the combination of doxorubicin and VCR is depicted as black dots (called “simultaneous application”). The expected apoptosis induction, if doxorubicin and VCR were given independently, was calculated from the results obtained with each drug alone as described in “Statistical analysis” and is shown as white and gray bars (called “independent application”). Definition of antagonistic, additive, and synergistic apoptosis is described in “Statistical analysis.”