Dose response of donor spleen cells necessary for the increased GVHD mortality by delayed bortezomib administration. (A-B) B6 (H2^b) recipients of BALB/c (H2^d)15 million BMCs with or without 15 million spleen cells (SCs) were treated with 15 μg bortezomib per dose daily. Morbidity was not observed in mice that received BMCs but not SCs and delayed bortezomib administration from day +5 through +7 (A) or bortezomib treatment from day 0 through +2 and from day +5 through +7 (B) after BMT. Significant decreases in survival were observed in delayed bortezomib-treated mice with SCs (▾, ▴) compared with delayed bortezomib-treated mice without SCs mice (•; panels A and B, P < .001). (C-E) B6 (H2^b) recipients of BALB/c (H2^d) 15 million bone marrow with 15 million (C), 10 million (D), or 5 million (E) SCs were treated with or without 15 μg bortezomib per dose daily. Delayed bortezomib treatment from day +12 through +14 after BMT accelerates GVHD mortality. Significant decreases in survival were observed in bortezomib-treated mice (▾) compared with mice that received PBS (no bortezomib-treatment; ▪; P < .005). Results from 1 of 3 independent experiments are presented. Each experiment consisted of 5 to 10 mice per treatment group.