Time-dependent administration of bortezomib produces differential scleroderma GVHD responses. Irradiated (8 Gy) BALB/c recipient mice were transplanted with bone marrow cells with or without spleen cells from donor B10.D2 mice. (A) Bortezomib or vehicle administration schema during cGVHD pathogenesis. (B) Body weight changes among different bortezomib regimen groups. (C) Comparison between early therapeutic bortezomib treatments vs vehicle control groups. (D) Comparison between vehicle control groups vs delayed bortezomib treatment groups. (E) Comparison between continuous therapeutic bortezomib treatments vs intermittent therapeutic bortezomib treatment groups. All the groups were tested simultaneously and repeated twice with 8 mice per group. Bortezomib was given at a dose of 0.1 mg/kg for all the groups except bone marrow only and vehicle control groups. The data are shown as mean ± SEM and were analyzed by 2-way ANOVA with a Tukey post hoc test to compare between groups. *P < .05 and ***P < .001 were considered significant.