Extended posttransplantation administration of bortezomib exacerbates GVHD-dependent mortality. Lethally irradiated (1000 cGy) B6 mice underwent transplantation with TCD B10.BR BM alone (□, n = 6) or with spleen cells adjusted to yield a dose of 2 × 106 B10.BR T cells. Mice that received transplanted B10.BR T cells were treated with PBS (•, n = 9) or bortezomib (▪, n = 9) (1 mg/kg twice weekly beginning on days 3-4). Survival is shown in panel A. In 2 additional experiments, cohorts of mice that underwent transplantation as in panel A were killed 6 to 7 days after BMT, and colon tissue was obtained for histologic analysis. Panel B shows pathology scores in the colons of mice that received TCD BM alone (□, n = 6) or with B10.BR T cells, followed by treatment with PBS (▨, n = 8) or bortezomib (▪, n = 7). In panels C and D, lethally irradiated B6 mice underwent transplantation with 10 × 106 B6.SJL BM cells and then were treated with twice-weekly PBS (□, n = 10) or bortezomib (▪, n = 10) (1 mg/kg/dose) beginning 3 to 4 days after BMT. Survival is shown in panel C, and panel D shows mean percentages of pretransplantation weight loss/gain. Data are cumulative results from 2 independent experiments for each strain combination (allogeneic and syngeneic).
