Summary of cellular kinetic parameters in peripheral blood by qPCR
| . | Pediatric B-ALL . | Adult ALL . | CLL . | Pooled ALL and CLL* . | |||||
|---|---|---|---|---|---|---|---|---|---|
| CR/CRi . | NR/PD . | CR/CRi . | NR/PD . | CR/CRi . | PR/PRi . | NR/PD . | CR/CRi/PR/PRi . | NR/PD . | |
| AUC0-28d, copies/µg × d | |||||||||
| n | 52 | 3 | 5 | 1 | 9 | 7 | 19 | 73 | 23 |
| Geometric mean | 342 731.8 | 104 566.7 | 485 033.4 | 172 471.2 | 168 375.4 | 424 663.4 | 5012.1 | 328 212.0† | 8 688.0 |
| CV% | 158.5 | 1170 | 206.6 | — | 559.5 | 395.4 | 1108.6 | 208.5 | 1 910.2 |
| AUC0-84d, copies/µg × d | |||||||||
| n | 43 | — | 3 | 1 | 7 | 7 | 10 | 60 | 11 |
| Geometric mean | 436 905.1 | — | 324 558.5 | 184 897.5 | 556 256.1 | 669 577.4 | 11 530.5 | 465 373.0 | 14 838.9 |
| CV% | 145.9 | — | 148.1 | — | 389 | 356.1 | 1600.3 | 178.2 | 1 721.1 |
| Cmax, copies/µg | |||||||||
| n | 50 | 3 | 5 | 1 | 8 | 7 | 22 | 70 | 26 |
| Geometric mean | 47 988.4 | 17 193.1 | 54 248.9 | 26 405.1 | 27 371.3 | 37 336.2 | 577.7 | 44 276.4† | 989.9 |
| CV% | 132.3 | 779.4 | 164.9 | — | 477.5 | 259.8 | 743.9 | 167.0 | 1 470.3 |
| Tmax, d | |||||||||
| n | 50 | 3 | 5 | 1 | 8 | 7 | 22 | 70 | 26 |
| Median | 11 | 13 | 11 | 8 | 14 | 16 | 15 | 11 | 15 |
| Range | 2-31 | 8-16 | 10-22 | — | 4-32 | 1-22 | 1-32 | 1-32 | 1-32 |
| T1/2, d | |||||||||
| n | 37 | 3 | — | — | 5 | 4 | 5 | 46 | 8 |
| Median | 14.2 | 1.9 | — | — | 41.3 | 21.6 | 10.1 | 18.8 | 8.8 |
| Range | 0.7-400 | 1.2-2.9 | — | — | 8.5-81.9 | 14.7-33.1 | 8.1-11.8 | 0.7-400 | 1.2-11.8 |
| Clast, copies/µg | |||||||||
| n | 33 | 1 | 5 | 1 | 8 | 7 | 22 | 53 | 24 |
| Geometric mean | 291.8 | 26.4 | 389.9 | 27.3 | 122.6 | 196.3 | 121.7 | 249.6 | 107.3 |
| CV% | 360.5 | — | 2443.3 | — | 186.1 | 188.1 | 187.4 | 355.3 | 193.6 |
| Tlast, d | |||||||||
| n | 33 | 1 | 5 | 1 | 8 | 7 | 22 | 53 | 24 |
| Median | 196 | 23 | 65 | 458 | 352 | 176 | 28.5 | 192 | 28.5 |
| Range | 18-780 | — | 59-742 | — | 56-772 | 79-429 | 1-177 | 18-780 | 1-32 |
| . | Pediatric B-ALL . | Adult ALL . | CLL . | Pooled ALL and CLL* . | |||||
|---|---|---|---|---|---|---|---|---|---|
| CR/CRi . | NR/PD . | CR/CRi . | NR/PD . | CR/CRi . | PR/PRi . | NR/PD . | CR/CRi/PR/PRi . | NR/PD . | |
| AUC0-28d, copies/µg × d | |||||||||
| n | 52 | 3 | 5 | 1 | 9 | 7 | 19 | 73 | 23 |
| Geometric mean | 342 731.8 | 104 566.7 | 485 033.4 | 172 471.2 | 168 375.4 | 424 663.4 | 5012.1 | 328 212.0† | 8 688.0 |
| CV% | 158.5 | 1170 | 206.6 | — | 559.5 | 395.4 | 1108.6 | 208.5 | 1 910.2 |
| AUC0-84d, copies/µg × d | |||||||||
| n | 43 | — | 3 | 1 | 7 | 7 | 10 | 60 | 11 |
| Geometric mean | 436 905.1 | — | 324 558.5 | 184 897.5 | 556 256.1 | 669 577.4 | 11 530.5 | 465 373.0 | 14 838.9 |
| CV% | 145.9 | — | 148.1 | — | 389 | 356.1 | 1600.3 | 178.2 | 1 721.1 |
| Cmax, copies/µg | |||||||||
| n | 50 | 3 | 5 | 1 | 8 | 7 | 22 | 70 | 26 |
| Geometric mean | 47 988.4 | 17 193.1 | 54 248.9 | 26 405.1 | 27 371.3 | 37 336.2 | 577.7 | 44 276.4† | 989.9 |
| CV% | 132.3 | 779.4 | 164.9 | — | 477.5 | 259.8 | 743.9 | 167.0 | 1 470.3 |
| Tmax, d | |||||||||
| n | 50 | 3 | 5 | 1 | 8 | 7 | 22 | 70 | 26 |
| Median | 11 | 13 | 11 | 8 | 14 | 16 | 15 | 11 | 15 |
| Range | 2-31 | 8-16 | 10-22 | — | 4-32 | 1-22 | 1-32 | 1-32 | 1-32 |
| T1/2, d | |||||||||
| n | 37 | 3 | — | — | 5 | 4 | 5 | 46 | 8 |
| Median | 14.2 | 1.9 | — | — | 41.3 | 21.6 | 10.1 | 18.8 | 8.8 |
| Range | 0.7-400 | 1.2-2.9 | — | — | 8.5-81.9 | 14.7-33.1 | 8.1-11.8 | 0.7-400 | 1.2-11.8 |
| Clast, copies/µg | |||||||||
| n | 33 | 1 | 5 | 1 | 8 | 7 | 22 | 53 | 24 |
| Geometric mean | 291.8 | 26.4 | 389.9 | 27.3 | 122.6 | 196.3 | 121.7 | 249.6 | 107.3 |
| CV% | 360.5 | — | 2443.3 | — | 186.1 | 188.1 | 187.4 | 355.3 | 193.6 |
| Tlast, d | |||||||||
| n | 33 | 1 | 5 | 1 | 8 | 7 | 22 | 53 | 24 |
| Median | 196 | 23 | 65 | 458 | 352 | 176 | 28.5 | 192 | 28.5 |
| Range | 18-780 | — | 59-742 | — | 56-772 | 79-429 | 1-177 | 18-780 | 1-32 |
A single patient (patient 117; supplemental Figure 3) had a Cmax value of 178 481.7 copies/µg, whereas the other 2 NR patients had values of 4694 and 6066 copies/µg. Although patient 117 had very high expansion by qPCR, limited expansion was observed by flow cytometry.
Data were pooled because there were insufficient data for statistical testing for each population separately. Although there were disease-specific differences between ALL and CLL, the trend for higher exposure among patients with CR/CRi and PR/PRi vs those with NR/PD across both diseases was the rationale for pooling the data.
P < .0001 (CR/CRi/PR/PRi vs NR/PD).