Pharmacologic Variables as Predictors of EFS
| . | Median . | Range . | P Value for Univariate Analysis . | P Value From Multivariate Analysis . | Association With Improved EFS . |
|---|---|---|---|---|---|
| Average TGN*(pmol/8 · 108 RBCs) (n = 709) | 401 | 0-1,498 | .611† | — | |
| Maximum TGN (pmol/8 · 108 RBCs) (n = 180) | 594 | 0-4,472 | .429† | — | |
| Average TIMP*(pmol/8 · 108 RBCs) (n = 709) | 69 | 0-256 | .640† | — | |
| Maximum TIMP (pmol/8 · 108 RBCs) (n = 180) | 131 | 0-456 | .509† | — | |
| Average MeTIMP*(pmol/8 · 108 RBCs) (n = 152) | 14,212 | 0-59,379 | .252† | — | |
| Maximum MeTIMP (pmol/8 · 108RBCs) (n = 86) | 16,532 | 0-68,371 | .287† | — | |
| TPMT activity (units/mL packed RBCs)* (n = 267) | 18.0 | 0.4-30.4 | .363† | .096† | Lower activity |
| Average MTXPGs* (pmol/109 RBCs) (n = 418) | 24.8 | 4.9-58.0 | .664† | — | |
| Maximum MTXPGs (pmol/109 RBCs) (n = 156) | 33.0 | 4.9-85.3 | .196† | .405† | |
| Average MTX AUC* (μmol · h) (n = 842) | 674 | 350-1,024 | .520‡ | — | |
| Average teniposide AUC* (μmol · h) (n = 830) | 731 | 235-1,454 | .914‡ | — | |
| Average cytarabine AUC*(μmol · h) (n = 811) | 58 | 12.7-443 | .362‡ | — | |
| Dose intensity 6MP1-153 (n = 19,046) | 83% | 11-170% | .006† | .022† | Higher dose intensity |
| Dose intensity MTX1-153 (n = 19,046) | 83% | 30-102% | .039† | .557† |
| . | Median . | Range . | P Value for Univariate Analysis . | P Value From Multivariate Analysis . | Association With Improved EFS . |
|---|---|---|---|---|---|
| Average TGN*(pmol/8 · 108 RBCs) (n = 709) | 401 | 0-1,498 | .611† | — | |
| Maximum TGN (pmol/8 · 108 RBCs) (n = 180) | 594 | 0-4,472 | .429† | — | |
| Average TIMP*(pmol/8 · 108 RBCs) (n = 709) | 69 | 0-256 | .640† | — | |
| Maximum TIMP (pmol/8 · 108 RBCs) (n = 180) | 131 | 0-456 | .509† | — | |
| Average MeTIMP*(pmol/8 · 108 RBCs) (n = 152) | 14,212 | 0-59,379 | .252† | — | |
| Maximum MeTIMP (pmol/8 · 108RBCs) (n = 86) | 16,532 | 0-68,371 | .287† | — | |
| TPMT activity (units/mL packed RBCs)* (n = 267) | 18.0 | 0.4-30.4 | .363† | .096† | Lower activity |
| Average MTXPGs* (pmol/109 RBCs) (n = 418) | 24.8 | 4.9-58.0 | .664† | — | |
| Maximum MTXPGs (pmol/109 RBCs) (n = 156) | 33.0 | 4.9-85.3 | .196† | .405† | |
| Average MTX AUC* (μmol · h) (n = 842) | 674 | 350-1,024 | .520‡ | — | |
| Average teniposide AUC* (μmol · h) (n = 830) | 731 | 235-1,454 | .914‡ | — | |
| Average cytarabine AUC*(μmol · h) (n = 811) | 58 | 12.7-443 | .362‡ | — | |
| Dose intensity 6MP1-153 (n = 19,046) | 83% | 11-170% | .006† | .022† | Higher dose intensity |
| Dose intensity MTX1-153 (n = 19,046) | 83% | 30-102% | .039† | .557† |
Abbreviations: RBC, red blood cell; TGN, thioguanine nucleotides; TIMP, thioinosine monophosphate; MeTIMP, methylthioinosine monophosphate; TPMT, thiopurine methyltransferase; MTXPG, methotrexate polyglutamates; AUC, plasma area under the concentration-times-time curve; MTX, methotrexate; 6MP, 6-mercaptopurine; n = number of measurements for each variable used in the analysis.
For those variables for which >1 measurement was taken per patient, the median and range of all possible values are indicated.
Stratified for risk group and protocol treatment arm (conventionalv targeted doses of pulse therapy).
Stratified for risk group only.
Dose intensity was estimated as the mg/m2/week of each drug administered ÷ the protocol scheduled dosage for all eligible weeks up until elective cessation of therapy or an event · 100%; n = number of weeks of therapy evaluated for the analysis.