In vitro combination of forodesine with fludarabine, bendamustine, and rituximab in primary CLL cells. (A) CI for forodesine 2 μM and dGuo 10 to 20 μM, with fludarabine (3.75 and 7.5 μM) or bendamustine (10 and 25 μM) in primary cells from 28 patients with CLL. Cell death was determined at 48 hours by annexin V binding as described in “Methods.” The black horizontal line represents the threshold between synergism (CI < 1) and antagonism (CI > 1). (B) Primary cells from 15 patients with CLL were treated with forodesine 2 μM and dGuo 10 or 20 μM, rituximab (25 and 50 μg/mL), or the combination of rituximab and forodesine for 24 hours. Percentage of cell viability (with respect to control) of 3 different patients with CLL and the mean of cell viability observed in 15 patients with CLL are shown. (C) CI for forodesine 2 μM and dGuo 10 or 20 μM with rituximab (25 and 50 μg/mL) or mafosfamide (1 and 2 μg/mL) in primary cells from 12 patients with CLL incubated for 24 hours. The black horizontal line represents the threshold between synergism (CI < 1) and antagonism (CI > 1). (D) Primary cells from patients with CLL were treated with forodesine 2 μM and dGuo 20 μM, mafosfamide (1 and 2 μg/mL), or the combination of forodesine and mafosfamide for 24 hours. Percentage of cell viability (with respect to control) of 3 representative patients with CLL and the mean of cell viability observed in 10 patients with CLL are shown.