Details of therapy in the randomized regimens
| Phase . | Drug . | Dose . | Schedule . |
|---|---|---|---|
| Induction (4 wk) | IT cytarabine | Age-adjusted* | Day 0 |
| Vincristine | 1.5 mg/m2 (2 mg max) | Days 0, 7, 14, 21 | |
| Pegaspargase† | 2500 U/m2 | Between days 3 and 5 | |
| Dexamethasone | 6 mg/m2/d | Days 0-27 | |
| IT MTX | Age-adjusted* | Days 7, 28 | |
| Consolidation (4 wk) | Vincristine | 1.5 mg/m2 (2 mg max) | Day 0 |
| Mercaptopurine | 75 mg/m2/d | Days 0-27 | |
| IT MTX | Age-adjusted* | Days 7, 14, 21 | |
| IM-1 (8 wk), OS/OD arms | Vincristine | 1.5 mg/m2 (2 mg max) | Days 0, 28 |
| Dexamethasone | 6 mg/m2/d | Days 0-4, 28-32 | |
| Mercaptopurine | 75 mg/m2/d | Days 0-49 | |
| MTX | 20 mg/m2/d | Weekly for 8 doses | |
| IT MTX | Age-adjusted* | Day 28 | |
| IM-1 (8 wk), IS/ID arms | Vincristine | 1.5 mg/m2 (2 mg max) | Every 10 days for 5 doses |
| IV MTX‡ | 100 mg/m2/d, starting dose | Every 10 days for 5 doses | |
| IT MTX | Age-adjusted* | Day 30 | |
| DI-1 (8 wk) | Vincristine | 1.5 mg/m2 (2 mg max) | Days 0, 7, 14 |
| Pegaspargase | 2500 U/m2/dose | Day 3 | |
| Dexamethasone | 10 mg/m2/d | Days 0-6, 14-20 | |
| Doxorubicin | 25 mg/m2/d | Days 0, 7, 14 | |
| Cytarabine | 75 mg/m2/d | Days 28-31, 35-38 | |
| Cyclophosphamide | 1000 mg/m2 | Day 28 | |
| Thioguanine | 60 mg/m2/d | Days 28-41 | |
| IT MTX | Age-adjusted* | Days 0, 28 | |
| IM-2(8 wk), OS/OD arms | Same as IM-1 with the addition of IT MTX on day 0 | ||
| IM-2 (8 wk), IS/ID arms§ | Same as IM-1 with the addition of IT MTX on day 0 | ||
| DI-2 (8 wk), only OD/ID | Same as DI-1 | ||
| Maintenance (12-wk cycles)‖ | Vincristine | 1.5 mg/m2 (2 mg max) | Days 0, 28, 56 |
| Dexamethasone | 6 mg/m2/d | Days 0-4, 28-32, 56-60 | |
| Mercaptopurine | 75 mg/m2/d | Daily | |
| MTX (oral) | 20 mg/m2/dose | Weekly | |
| IT MTX | Age-adjusted* | Day 0 |
| Phase . | Drug . | Dose . | Schedule . |
|---|---|---|---|
| Induction (4 wk) | IT cytarabine | Age-adjusted* | Day 0 |
| Vincristine | 1.5 mg/m2 (2 mg max) | Days 0, 7, 14, 21 | |
| Pegaspargase† | 2500 U/m2 | Between days 3 and 5 | |
| Dexamethasone | 6 mg/m2/d | Days 0-27 | |
| IT MTX | Age-adjusted* | Days 7, 28 | |
| Consolidation (4 wk) | Vincristine | 1.5 mg/m2 (2 mg max) | Day 0 |
| Mercaptopurine | 75 mg/m2/d | Days 0-27 | |
| IT MTX | Age-adjusted* | Days 7, 14, 21 | |
| IM-1 (8 wk), OS/OD arms | Vincristine | 1.5 mg/m2 (2 mg max) | Days 0, 28 |
| Dexamethasone | 6 mg/m2/d | Days 0-4, 28-32 | |
| Mercaptopurine | 75 mg/m2/d | Days 0-49 | |
| MTX | 20 mg/m2/d | Weekly for 8 doses | |
| IT MTX | Age-adjusted* | Day 28 | |
| IM-1 (8 wk), IS/ID arms | Vincristine | 1.5 mg/m2 (2 mg max) | Every 10 days for 5 doses |
| IV MTX‡ | 100 mg/m2/d, starting dose | Every 10 days for 5 doses | |
| IT MTX | Age-adjusted* | Day 30 | |
| DI-1 (8 wk) | Vincristine | 1.5 mg/m2 (2 mg max) | Days 0, 7, 14 |
| Pegaspargase | 2500 U/m2/dose | Day 3 | |
| Dexamethasone | 10 mg/m2/d | Days 0-6, 14-20 | |
| Doxorubicin | 25 mg/m2/d | Days 0, 7, 14 | |
| Cytarabine | 75 mg/m2/d | Days 28-31, 35-38 | |
| Cyclophosphamide | 1000 mg/m2 | Day 28 | |
| Thioguanine | 60 mg/m2/d | Days 28-41 | |
| IT MTX | Age-adjusted* | Days 0, 28 | |
| IM-2(8 wk), OS/OD arms | Same as IM-1 with the addition of IT MTX on day 0 | ||
| IM-2 (8 wk), IS/ID arms§ | Same as IM-1 with the addition of IT MTX on day 0 | ||
| DI-2 (8 wk), only OD/ID | Same as DI-1 | ||
| Maintenance (12-wk cycles)‖ | Vincristine | 1.5 mg/m2 (2 mg max) | Days 0, 28, 56 |
| Dexamethasone | 6 mg/m2/d | Days 0-4, 28-32, 56-60 | |
| Mercaptopurine | 75 mg/m2/d | Daily | |
| MTX (oral) | 20 mg/m2/dose | Weekly | |
| IT MTX | Age-adjusted* | Day 0 |
IT indicates intrathecal; MTX, methotrexate; IM, interim maintenance phase; OS, included regimen of PO MTX, mercaptopurine, vincristine, and dexamethasone (during the IM phases) and single delayed intensification; OD, included regimen of PO MTX, mercaptopurine, vincristine, and dexamethasone (during the IM phases) and double delayed intensification; IS, included regimen of IV MTX and vincristine (during the IM phases) and single delayed intensification; ID, included regimen of IV MTX and vincristine (during the IM phases) and double delayed intensification; and DI, delayed intensification phase.
IT cytarabine was adjusted for age as follows: 1-1.99 years, 30 mg; 2-2.99 years, 50 mg; > 3 years, 70 mg. IT MTX was adjusted for age as follows: 1-1.99 years, 8 mg; 2-2.99 years, 10 mg; > 3 years, 12 mg.
Asparaginase preparation: pegylated asparaginase; Erwinia asparaginase replaced pegaspargase after severe allergic reactions.
IV MTX initial dose was 100 mg/m2; dose was escalated by 50 mg/m2 every 10 days (± 2 days) for 4 doses, to toxicity.
Starting dose of IV MTX is two-thirds maximum tolerated dose in IM-1.
Total duration of treatment for boys was 38 months and girls was 26 months.