Attenuation of lethal GVHD in murine allogeneic BMT recipients by targeting JAK3 with WHI-P131
| Treatment protocol . | n . | MST (d) . | Cumulative proportion surviving (% ± SEM) . | P(Log-rank) . | |||
|---|---|---|---|---|---|---|---|
| 30 d . | 60 d . | 85 d . | vs B . | vs C . | |||
| A. TBI + syngeneic BMT | 19 | > 85 | 100 ± 0 | 100 ± 0 | 100 ± 0 | — | — |
| B. TBI + Allo-BMT (H-2d to H-2b) + vehicle* | 38 | 37 | 68 ± 8 | 11 ± 5 | 0 ± 0 | — | < .0001 |
| C. TBI + Allo-BMT (H-2d to H-2b) + WHI-P131 | 32 | 56 | 94 ± 4 | 41 ± 9 | 19 ± 7 | < .0001 | — |
| D. TBI + Allo-BMT (H-2d to H-2b) + WHI-P131 delayed treatment | 14 | 54 | 93 ± 7 | 43 ± 13 | 14 ± 9 | .007 | NS |
| E. TBI + Allo-BMT (H-2d to H-2b) + WHI-P132 | 9 | 44 | 89 ± 11 | 11 ± 11 | 0 ± 0 | NS | .02 |
| F. TBI + Allo-BMT (H-2d to H-2b) + WHI-P132 delayed treatment | 9 | 35 | 89 ± 11 | 0 ± 0 | 0 ± 0 | NS | .0002 |
| G. TBI + Allo-BMT (H-2d to H-2b) + MTX | 16 | 63 | 94 ± 6 | 56 ± 12 | 25 ± 11 | < .0001 | NS |
| H. TBI + Allo-BMT (H-2d to H-2b) + WHI-P131 + MTX2-160 | 23 | > 85 | 100 ± 0 | 78 ± 9 | 70 ± 10 | < .0001 | .0001 |
| Treatment protocol . | n . | MST (d) . | Cumulative proportion surviving (% ± SEM) . | P(Log-rank) . | |||
|---|---|---|---|---|---|---|---|
| 30 d . | 60 d . | 85 d . | vs B . | vs C . | |||
| A. TBI + syngeneic BMT | 19 | > 85 | 100 ± 0 | 100 ± 0 | 100 ± 0 | — | — |
| B. TBI + Allo-BMT (H-2d to H-2b) + vehicle* | 38 | 37 | 68 ± 8 | 11 ± 5 | 0 ± 0 | — | < .0001 |
| C. TBI + Allo-BMT (H-2d to H-2b) + WHI-P131 | 32 | 56 | 94 ± 4 | 41 ± 9 | 19 ± 7 | < .0001 | — |
| D. TBI + Allo-BMT (H-2d to H-2b) + WHI-P131 delayed treatment | 14 | 54 | 93 ± 7 | 43 ± 13 | 14 ± 9 | .007 | NS |
| E. TBI + Allo-BMT (H-2d to H-2b) + WHI-P132 | 9 | 44 | 89 ± 11 | 11 ± 11 | 0 ± 0 | NS | .02 |
| F. TBI + Allo-BMT (H-2d to H-2b) + WHI-P132 delayed treatment | 9 | 35 | 89 ± 11 | 0 ± 0 | 0 ± 0 | NS | .0002 |
| G. TBI + Allo-BMT (H-2d to H-2b) + MTX | 16 | 63 | 94 ± 6 | 56 ± 12 | 25 ± 11 | < .0001 | NS |
| H. TBI + Allo-BMT (H-2d to H-2b) + WHI-P131 + MTX2-160 | 23 | > 85 | 100 ± 0 | 78 ± 9 | 70 ± 10 | < .0001 | .0001 |
In 2 independent experiments, summarized in this table, C57BL/6 (H-2b) recipients were lethally irradiated (TBI, 7.5 Gy) and transplanted with BM/S grafts from MHC-disparate BALB/c (H-2d) mice and subjected to the treatment regimens presented above (the details of these treatment regimens are given in “Materials and methods)”;
P = .009 compared to group G; statistically significant differences obtained by life table analysis (log-rank test).
MST of control group B was 40 days in the first experiment involving 15 control mice and 33 days in the second experiment involving 23 control mice. The cumulative proportion of control mice surviving at 60 days was 13% ± 9% in the first experiment and 9% ± 6% in the second experiment. No control mouse was alive at 85 days in either of these two experiments. The weight curves were obtained in the first but not the second experiment to minimize the handling of mice and the associated stress.