Effects of the JAK3 inhibitor WHI-P131/JANEX-1 on post-BMT survival outcome in murine GVHD and GVL models
| Treatment protocol . | N . | MST . | Cumulative proportion surviving (% ± SEM) . | |
|---|---|---|---|---|
| d . | 30 d . | 60 d . | ||
| A. BCL-1 → vehicle | 20 | 12 | 0 ± 0 | 0 ± 0 |
| B. BCL-1 → WHI-P131, 75 mg/kg/d | 20 | 11 | 0 ± 0 | 0 ± 0 |
| C. BCL-1 → WHI-P131, 150 mg/kg/d | 20 | 12 | 0 ± 0 | 0 ± 0 |
| D. TBI | 5 | 11 | 0 ± 0 | 0 ± 0 |
| E. TBI + syngeneic BMT → vehicle | 5 | > 60 | 100 ± 0 | 100 ± 0 |
| F. TBI + syngeneic BMT + BCL-1 → vehicle | 22 | 14 | 14 ± 7 | 0 ± 0 |
| G. TBI + syngeneic BMT + BCL-1 → WHI-P131 | 13 | 12 | 8 ± 7 | 0 ± 0 |
| H. TBI + allo BMT → vehicle | 23 | 24 | 9 ± 6 | 0 ± 0 |
| I. TBI + allo BMT → WHI-P131 | 17 | 37 | 60 ± 12 | 29 ± 11 |
| J. TBI + allo BMT + BCL-1 → vehicle | 28 | 25 | 11 ± 6 | 4 ± 4 |
| K. TBI + allo BMT + BCL-1 → WHI-P131 | 16 | 36 | 63 ± 12 | 44 ± 12 |
| Treatment protocol . | N . | MST . | Cumulative proportion surviving (% ± SEM) . | |
|---|---|---|---|---|
| d . | 30 d . | 60 d . | ||
| A. BCL-1 → vehicle | 20 | 12 | 0 ± 0 | 0 ± 0 |
| B. BCL-1 → WHI-P131, 75 mg/kg/d | 20 | 11 | 0 ± 0 | 0 ± 0 |
| C. BCL-1 → WHI-P131, 150 mg/kg/d | 20 | 12 | 0 ± 0 | 0 ± 0 |
| D. TBI | 5 | 11 | 0 ± 0 | 0 ± 0 |
| E. TBI + syngeneic BMT → vehicle | 5 | > 60 | 100 ± 0 | 100 ± 0 |
| F. TBI + syngeneic BMT + BCL-1 → vehicle | 22 | 14 | 14 ± 7 | 0 ± 0 |
| G. TBI + syngeneic BMT + BCL-1 → WHI-P131 | 13 | 12 | 8 ± 7 | 0 ± 0 |
| H. TBI + allo BMT → vehicle | 23 | 24 | 9 ± 6 | 0 ± 0 |
| I. TBI + allo BMT → WHI-P131 | 17 | 37 | 60 ± 12 | 29 ± 11 |
| J. TBI + allo BMT + BCL-1 → vehicle | 28 | 25 | 11 ± 6 | 4 ± 4 |
| K. TBI + allo BMT + BCL-1 → WHI-P131 | 16 | 36 | 63 ± 12 | 44 ± 12 |
(BALB/cJxC57BL/6J)F1 (H-2d/b) recipients were lethally irradiated (9.5 Gy) and transplanted with BM/S grafts from syngeneic F1 or allogeneic C57BL/6 (H-2b) donors. In protocols A, B, and C, 1 × 106 BCL-1 cells were injected intravenously. In protocols F, G, J, and K, 5 × 106 BCL-1 were injected intravenously. In all GVHD and GVL groups (G, I, K), the dose of WHI-P131 was 50 mg/kg per day.
P < .0001 between groups J and K, H and I, E and F, D and E; there were no significant differences between groups H and J, F and G, I and K. Statistically significant differences were obtained by life-table analysis (log-rank test).