In vivo therapeutic evaluation of FTY720 in a SCID xenograft mouse model of disseminated lymphoma/leukemia. (A) Survival analysis of FTY720-treated mice. A total of 52 female 6- to 8-week-old C.B.-17 SCID mice were injected with 2 × 10⁶ Raji cells intravenously by tail vein in 200 μL sterile PBS. At 74 hours after inoculation, the animals were divided into 4 equal treatment groups. The first 3 groups served as controls and received vehicle, trastuzumab, or rituximab injection (5 mg/kg) 3 times a week for 2 weeks; the fourth group consisted of animals treated with FTY720 (5 mg/kg) every day for 2 weeks intraperitoneally. All the animals were monitored daily for signs of illness and killed immediately if hind-limb paralysis, respiratory distress, or 30% body weight loss was noted. The endpoint of the study was survival defined as the time for the development of hind-limb paralysis. The median survival time for FTY720-treated mice was 47 days (95% CI, 39-53). This is significantly prolonged compared with placebo controls (18 days; 95% CI, 17-19; FTY720 vs placebo, P < .001). (B) Depletion of infiltrated human CD45⁺ cells in FTY720-treated mice, but not in control mice. Histologic (hematoxylin and eosin staining) analysis of lymph node (top panels) and thymus (bottom panels) from control untreated (left panels) or FTY720-treated (right panels) mice. Insert shows immunohistochemical analysis of human CD45⁺ cells in the respective sections from untreated and FTY720 treated mice. (C) Flow cytometric analysis of bone marrow cells from Raji cells engrafted mice at day 17 after inoculation. Mice were treated with placebo or FTY720, and the percentage of human CD19⁺ cells in the bone marrow were analyzed by flow cytometry using anti-human CD19 antibody that detects the human (Raji) but not mouse B cells.