Effects of delayed bortezomib administration on pathologic damage to target organs of GVHD. Significant increases in histologic changes were observed in the small and large intestine, but not the liver, of mice treated with delayed bortezomib on day +12 or day +12 through day +13 at 15 μg/mouse (intravenously). Mice were assessed 16 hours after a single bortezomib or vehicle control (VC) injection (day +12) or 6 hours after a second injection (day +13) of bortezomib or VC, respectively. Three 3 to 6 mice per experimental group in each of 4 independent experiments were assessed. Tissues were assessed for histologic changes in 3 to 4 parameters as described in “Materials and methods” and the sum of these scores are represented for each tissue. Histologic changes for each parameter were assessed and graded where 0 = normal, 1 = minimal, 2 = mild, 3 = moderate, and 4 = severe. Comparison of cumulative histopathologic scores between the groups with splenocytes were analyzed by Mann-Whitney test (P < .05).