Table 1.
Summary of survival, clinical scores, weights, and histopathologic assessments by PTCy dose.
| PTCy Dose | Survival | Clinical Scores | Weights | Histopathology |
|---|---|---|---|---|
| 5 mg/kg | • Dosing on days +3/+4 resulted in
improved survival compared with days +2/+3 (not statistically
significant, p=0.061) • No significant differences between dosing on days +3/+4, +4/+5, or +3/+5; none significantly prolonged survival compared with vehicle |
• No significant difference between
dosing on days +3/+4 or +2/+3 • No significant differences between dosing on days +3/+4, +4/+5, or +3/+5 |
• No significant difference between
dosing on days +3/+4 or +2/+3 • No significant differences between dosing on days +3/+4, +4/+5, or +3/+5 |
• Not performed |
| 10 mg/kg | • Dosing on days +1/+2 led to
accelerated death compared with vehicle (p=0.0019) • Dosing on days +3/+4 (p<0.0001) or +5/+6 (p=0.0005) significantly prolonged survival compared with vehicle; dosing on days +7/+8 did not prolong survival • Dosing on days +3/+4 significantly prolonged survival compared with days +1/+2 (p<0.0001) or +7/+8 (p=0.0002), but not days +5/+6 (p=0.19) • Dosing on days +3/+4 significantly prolonged survival compared with days +2/+3 (p=0.0075) • Dosing on days +3/+4 (p=0.0054) or +4/+5 (p=0.0001) significantly prolonged survival compared with vehicle, but the effect of dosing on days +3/+5 was less (p=0.06); no significant differences between these dosing schedules • Dosing on day +4 only (p=0.14) or 5 mg/kg/dose BID on days +3/+4 (p=0.058) were only partially effective in prolonging survival compared with vehicle; dosing on day +3 only did not prolong survival |
• Dosing on days +3/+4 resulted in
significantly better scores compared with vehicle-treated mice
(p<0.001) and was superior to dosing on days +1/+2, +5/+6, or
+7/+8 • Dosing on days +3/+4 resulted in significantly better scores than days +2/+3 (p=0.011) • No significant differences between dosing on days +3/+4, +4/+5, or +3/+5; all three dosing schedules were significantly better than vehicle (p=0.0002, p=0.0001, and p=0.0052, respectively) • Dosing on days +3/+4, day +3 only, day +4 only, or 5 mg/kg/dose BID on days +3/+4 resulted in significantly better scores than vehicle (p<0.0001 for all except day +3 only (p=0.035)); dosing on day +3 only resulted in significantly worse scores than other dosing schedules (p=0.0005 vs. days +3/+4, p=0.024 vs. day +4 only, p=0.017 vs. 5 mg/kg/dose BID on days +3/+4), but there were no significant differences between the other dosing groups |
• Dosing on days +3/+4 resulted in
significantly better weights compared with vehicle (p=0.023) and was
superior to dosing on days +1/+2, +5/+6, or
+7/+8 • No significant difference between dosing on days +3/+4 or +2/+3 • No significant differences between dosing on days +3/+4, +4/+5, or +3/+5; all three dosing schedules were significantly better than vehicle (p=0.04, p=0.0002, and p=0.004, respectively) • No significant differences between dosing on days +3/+4, day +3 only, day +4 only, or 5 mg/kg/dose BID on days +3/+4 |
• Day 7: No significant differences
compared with vehicle for dosing on days +1/+2 or
+3/+4 • Day 21: Dosing on days +3/+4 resulted in significantly less GVHD than vehicle (p=0.026); no significant differences compared with vehicle for dosing on days +2/+3, +5/+6, or +7/+8 |
| 25 mg/kg | • Dosing on days +1/+2, +3/+4, +5/+6,
or +7/+8 all significantly prolonged survival compared with vehicle
(p=0.0039, p=0.0001, p=0.0084, and p=0.0021, respectively); dosing on
days +3/+4 significantly prolonged survival compared with days +7/+8
(p=0.0045) but not days +1/+2 (p=0.24) or +5/+6
(p=0.11) • No significant difference between dosing on days +3/+4 or +2/+3 • No significant differences between dosing on days +3/+4, +4/+5, or +3/+5; all three dosing schedules significantly prolonged survival compared with vehicle (p=0.0002, p=0.0001, and p=0.0002, respectively) • Dosing of 50 mg/kg on day +3 only resulted in significantly worse survival compared with 25 mg/kg on day +4 only (p=0.029) or 12.5 mg/kg/dose BID on days +3/+4 (p=0.019); no significant differences between 50 mg/kg on day +3 only and 25 mg/kg/day on days +3/+4 or day +3 only; no significant differences between 25 mg/kg on day +3 only, 25 mg/kg on day +4 only, 25 mg/kg/day on days +3/4, or 12.5 mg/kg/dose BID on days +3/+4 |
• Dosing on days +3/+4 resulted in
significantly better scores compared with vehicle (p<0.0001) or
dosing on days +1/+2, +5/+6, or +7/+8 (p<0.0001 for all three
comparisons) • No significant difference between dosing on days +3/+4 or +2/+3 • No significant differences between dosing on days +3/+4, +4/+5, or +3/+5 • No significant differences between dosing of 12.5 mg/kg/dose BID on days +3/+4 or 25 mg/kg/day on day +3 only, day +4 only, or days +3/+4; dosing of 50 mg/kg on day +3 only resulted in significantly worse scores compared with 12.5 mg/kg/dose BID on days +3/+4 (p=0.014) |
• Dosing on days +3/+4 resulted in
superior weights compared with vehicle (p=0.0007) or dosing on days
+1/+2, +5/+6, or +7/+8 (p=0.0011, p=0.052, and p=0.015,
respectively) • No significant difference between dosing on days +3/+4 or +2/+3 • No significant differences between dosing on days +3/+4, +4/+5, or +3/+5 • No significant differences between dosing of 50 mg on day +3 only, 12.5 mg/kg/dose BID on days +3/+4, or 25 mg/kg/day on either days +3/+4, +3 only, or +4 only |
• Day 7: Dosing on days +3/+4 resulted
in significantly less GVHD compared with vehicle (p<0.001) but
dosing on days +1/+2 did not result in less histopathologic GVHD
compared with vehicle • Day 21: Dosing on days +1/+2, +3/+4, +5/+6, or +7/+8 resulted in significantly less GVHD compared with vehicle (p<0.0001 for each comparison except p=0.0019 for days +7/+8); dosing on days +3/+4 resulted in the least histopathologic GVHD |
Note: The data reported for the clinical scores and weights refer to the comparisons of area under the curve (AUC) analyses over the time points in which there were ≥7 mice per group as per the figure legends for each set of experiments; the only exception was the for the 10 mg/kg groups in Figure 1 in which all mice treated with 10 mg/kg/day PTCy on days +1/+2 died rapidly and so the AUC comparisons were over days 0–21, after which there were <7 mice in the vehicle-treated group.