Pharmacologic inhibition of Cdk5 after HCT reduces clinical GVHD severity and while maintaining potent GVL effects. Lethally irradiated B6D2F1 mice received HCT from either syngeneic B6D2F1 or allogeneic (B6) mice as described in Figure 2. Groups of mice received 500 P815 cells previously transduced using a lentiviral vector carrying a luciferase reporter that allows visualization of proliferating cells using bioluminescence imaging (BLI). Syngeneic and allo-HCT recipients were monitored for tumor progress (A) and clinical GVHD severity (B). Roscovitine, at the dose and schedule administered after HCT effectively inhibited Cdk5 activity measured in spleens of mice collected on day 7 posttransplant (C). Data shown are representative of 2 replicate experiments: n = 5 to 12 mice per group; P < .01. Note: A single mouse in the allo-HCT group receiving roscovitine unexpectedly died following anesthesia for BLI and was censored “C”. Radiance is expressed as p/sec/cm²/sr. Color scale: Min = 2.00e4, Max = 2.00e5.