Effects of WHI-P131/JANEX-1 with or without MTX on survival.

The effects of the JAK3 inhibitor WHI-P131 (A) or WHI-P131 in combination with MTX (B) on the post-BMT survival outcome in a murine GVL model are shown. Irradiated (9.5 Gy) (BALB/cJxC57BL/6J) F1 (H-2^d/b) recipients were given BM/S graft (25 × 10⁶ cells of each) from syngeneic (syngeneic BMT) or allogeneic C57BL/6 (H-2^b) donors (allo BMT). BMT recipients (GVL model) were injected with 5 × 10⁶ leukemia/lymphoma BCL-1 cells on day 0. Recipients were treated with vehicle alone (A), WHI-P131 (50 mg/kg per day in 2 divided doses) alone (A,B), MTX (10 mg/m² per day, single daily dose) alone (B), or WHI-P131 (50 mg/kg per day in 2 divided doses) plus MTX (10 mg/m² per day, single daily dose; panel B) daily from day 0 until day 60 after BMT. Because there were no differences in survival rate of syngeneic BMT recipients treated with vehicle (n = 22) or with WHI-P131 (n = 13; Table1), they were summarized and presented as syngeneic BMT+BCl-1 group (n = 35; A). Controls (B) included mice inoculated with BCL-1 cells but not transplanted; some of these mice were treated with MTX alone.P < .0001 (WHI-P131–treated allogeneic BMT group versus vehicle-treated allogeneic BMT group, log-rank test, panel A);P < .001 (WHI-P131 or MTX versus no GVHD prophylaxis, log-rank test); P < .01 (WHI+MTX versus all other groups, log- rank test, panel B).