Table 3.
Post-transplant pharmacologic biomarkers and clinical outcomes
| Cyclophosphamide (μM×hr) | Total MPA AUC0-8hr (μg/mL×hr) | Free MPA AUC0-8hr (ng/mL×hr) | IMPDH AUEC (pmol × 106 cells) | Outcome (days) | Length of follow-up (months) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Patient | CY | 4HCY | CEPM | DCCY | KetoCY | Day +7 | Day +21 | Day +7 | Day +21 | |||
| One CY dose (day +3); AUC0-24hr | ||||||||||||
| 3 | 2760 | 41.0 | 80.5 | 223 | 56.0 | 20.23 | 12.74 | 327 | 161 | 5676 | Deceased; relapse (85) | |
| 4 | 2663 | 65.2 | 133 | 215 | 69.8 | 35.35 | 25.18 | 469 | 305 | 4858 | Relapsed (534), now in CR | 25 |
| 10 | 1932 | 58.3 | 142 | 227 | 79.2 | 12.90 | 9.25 | 170 | 141 | 4039 | Deceased; relapse (46) | |
| Two CY doses (days +3 and +4); AUC0-48hr | ||||||||||||
| 1 | 3839 | 228 | 520 | 297 | 184 | 21.60 | 15.55 | 237 | 208 | 1532 | 29 | |
| 2 | 4796 | 174 | 489 | 508 | 158 | 9.83 | 8.51 | 158 | 145 | 5781 | Deceased; ARDSa, renal failure; on ISPb (265) | |
| 5 | 4295 | 116 | 321 | 211 | 89.0 | 23.18 | 15.25 | 432 | 235 | 1171 | Deceased; pneumonia; on ISPb (126) | |
| 6 | 3812 | 121 | 160 | 555 | 95.5 | 12.09 | --c | 154 | -- | -- | 23 | |
| 7 | 3685 | 134 | 228 | 258 | 122 | 9.46 | 11.46 | 192 | 179 | 4377 | Deceased; MOF with GVHD; on ISPb,d (259) | |
| 8 | 3123 | 120 | 269 | 635 | 111 | 12.20 | --c | 238 | -- | -- | 16 | |
| 9 | 3425 | 35.7e | 408 | 283 | 132 | 10.50 | 6.77 | 181 | 108 | 1930 | 15 | |
| 11 | 2754 | 150 | 161 | 423 | 169 | 10.44 | --c | 196 | -- | -- | 14 | |
| Median (range)f | 3748 (2754 – 4796) | 134 (116 – 228) | 295 (160 – 520) | 360 (211 – 635) | 127 (89.0 – 184) | 12.20 (9.46 – 35.35) | 12.10 (6.77 – 25.18) | 196 (154 – 469) | 170 (108 – 305) | 4208 (1171 – 5781) | ||
| Fold rangef | 1.7 | 2.0 | 3.2 | 3.0 | 2.1 | 3.7 | 3.7 | 3.0 | 2.8 | 4.9 | ||
a
Acute respiratory distress syndrome;
b
Immunosuppression; pt was on immunosuppressants at time of death;
c
Patients 6, 8, and 11 declined to participate in the second of the two MMF pharmacokinetic sampling days;
d
Multi-organ failure with graft versus host disease;
e
4HCY pharmacokinetics only collected with first dose of CY; due to delay in second dose, 4HCY derivatizing agent was no longer viable at time of sample collection;
f
Median and fold range values include only those patients receiving two doses of post-transplant CY.