Synergistic effect of XIAP inhibitors on CD95-mediated apoptosis. (A) CLL cells of 16 patients were activated via CD40 ligation and examined 1 day later for sensitivity to CD95-mediated apoptosis. The activated CLL cells were treated with either medium alone, CH11, different concentrations of 1540-14, or CH11 and 1540-14 at various concentrations. After 24 hours, the relative percent number of cells undergoing apoptosis was measured by flow cytometry. The data are expressed as percent specific apoptosis as defined in “Patients, materials, and methods.” The differences in the level of apoptosis between cells treated with CH11 alone versus that of cells treated with CH11 and 1540-14 was statistically significant at all concentrations. An asterisk indicates that the level of apoptosis achieved with CH11 and 1540-14 was significantly greater than that achieved with 1540-14 alone at the indicated concentration. (B) CLL cells of 13 patients were activated via CD40 ligation and examined 3 days later for sensitivity to CH11. The differences in the level of apoptosis between treatment with CH11 alone and treatment with CH11 and 1540-14 were statistically significant only at 10 μM and 15 μM (P < .05). An asterisk indicates that the level of apoptosis achieved with CH11 and 1540-14 was significantly greater than that achieved with 1540-14 alone at the indicated concentration of 1540-14. Error bars indicate SD about the mean.