RAD001 improves survival of NOD/SCID mice engrafted with ALL. (A) Percentage of human ALL cells in the blood of mice engrafted with the indicated samples over time. Mice were treated with vehicle, vincristine (Vin), RAD001, or RAD001 and vincristine (RAD + Vin). The time indicated is from the commencement of treatment, and the arrow indicates the completion of treatment. Mean plus or minus SD of surviving animals is shown. (B) Kaplan-Meier plots of the survival of mice engrafted with xenografts from 5 patients with childhood ALL. The time indicated is from the commencement of treatment, and the arrow represents the completion of treatment. (C) Femur (i-iii) or vertebral body hematoxylin and eosin–stained sections (iv) from mice engrafted with ALL-1999 10 weeks after the completion of treatment with RAD001 (i,iii,iv) or RAD001 + vincristine (ii). Subpanels i and ii show normal hematopoiesis, whereas subpanels iii and iv are from the single animal showing disease relapse at the time of death. Regions of leukemic infiltration are indicated by arrows. Original magnification ×200 (details in “Histology”). Larger images available in Figure S2. (D) Murine white blood cell counts (mean ± SD) of surviving NOD/SCID mice engrafted with ALL-1999 during and after the completion of treatment. Time is from the initiation of treatment and the end of treatment indicated by the arrow. The white cell counts were very low at the start of treatment because the mice were still recovering from the sublethal radiation administered to facilitate ALL engraftment. The shaded area represents the normal range; line, mean value for white blood cell counts observed in our NOD/SCID mouse colony. Note that the vehicle- and vincristine-treated mice had all died of disease by day 20.