Delayed administration of bortezomib results in lethal toxicity in murine models of GVHD. (A) B6 (H2^b) recipients of 15 million BALB/c (H2^d) BMCs and 12 million spleen cells (SCs) were treated with or without 15 μg bortezomib per dose on days 0 to 1 or 5 to 6 after BMT (n = 6-7 mice/group). Representative data from 1 of 2 independent experiments are shown. (B) BALB/c (H2^d) recipients of 10 million FvB (H2^q) BMCs and 2 million SCs were treated with or without 7.5 μg bortezomib per dose on days 0 or 5 after BMT. Representative data from 1 of 2 independent experiments are shown. (C,D) B6 (H2^b) recipients underwent transplantation and were treated with bortezomib on day + 5 after BMT as described in panel A. Serum was collected 12 hours after bortezomib administration and analyzed for TNFα and IFNγ levels (n = 3-8 mice/group). Representative data from 1 of 2 independent experiments are shown. Results are shown as means plus or minus SEM. (E,F) BALB/c (H2^d) recipients of 10 million FvB (H2^q) BMCs and 2 million SCs were treated with or without 7.5 μg bortezomib on day 5 after BMT. Serum was collected 12 hours after bortezomib administration and analyzed for TNFα and IFNγ levels (n = 5 mice/group). Results are shown as means plus or minus SEM. Representative data from 1 of 2 independent experiments.