Selumetinib inhibits GVHD in MHC-mismatched murine SCT. BALB/c recipients were irradiated (7.5Gy) on day −1 and infused (on day 0) with 5 × 106 B6 TCD-BM cells and 0.6 × 106 B6 T cells. B6 T cells were incubated with selumetinib or control (DMSO) for 30 minutes at 37°C before adoptive transfer. Murine recipients were administered vehicle or selumetinib (25 mg/kg) once daily via gavage from day 0 through day 7, and analyzed for survival. Engraftment of donor cells in recipient spleen, BM, and thymus was consistently demonstrated in all groups (not shown). Median survival was prolonged in mice receiving selumetinib (median of 34 days) vs control animals (median 10 days in vehicle-treated animals receiving T-replete grafts; P value 0.01 by log rank comparison using the Grehan-Breslow-Wilcoxon test). As expected, median survival was not reached in mice receiving marrow alone). Combined data from 2 independent experiments is shown, based on n = 14 animals (BM only), n = 16 (vehicle), and n = 12 (selumetinib) in total.
