Standard therapy and increased intensity postinduction intensification therapy regimens
| Standard therapy . | Increased intensity therapy . | ||
|---|---|---|---|
| Phase and treatment . | Dose . | Phase and treatment . | Dose . |
| Consolidation (5 wk) | Consolidation (9 wk) | ||
| Cyclophosphamide | 1000 mg/m2 per day IV, days 0, 14 | Cyclophosphamide | 1000 mg/m2 per day IV, days 0, 28 |
| Cytarabine | 75 mg/m2 per day IV, days 1-4, 8-11, 15-18, 22-25 | Cytarabine | 75 mg/m2 per day SQ IV, days 1-4, 8-11, 29-32, 36-39 |
| Mercaptopurine | 60 mg/m2 per day PO, days 0-27 | Mercaptopurine | 60 mg/m2 per day PO, days 0-13, 28-41 |
| Methotrexate* | IT, days 1, 8, 15, 22 | Methotrexate‡ | IT, days 1,8, 15, 22 |
| — | PEG asparaginase | 2500 U/m2 per day IM, days 14, 42 | |
| — | Vincristine | 1.5mg/m2 per day, days 14, 21, 42, 49 | |
| Interim maintenance (8 wk) | Interim maintenance I (7 wk) | ||
| Mercaptopurine | 60 mg/m2 per day PO, days 0-41 | Vincristine | 1.5 mg/m2 per day IV, days 0, 10, 20, 30, 40 |
| Methotrexate | 15 mg/m2 per day PO, days 0, 7, 14, 21, 28, 35 | Methotrexate | 100 mg/m2 per day IV, days 0, 10, 20, 30, 40 (escalate by 50 mg/m2 per dose) |
| — | PEG asparaginase | 2500 U/m2 per day IM, days 1, 21 | |
| Methotrexate* | IT days 0, 28 | Methotrexate* | IT days, 0. 30 |
| Delayed intensification (7 wk) | Delayed intensification (8 wk) | ||
| Reinduction (4 wk) | Reinduction (4 wk) | ||
| Dexamethasone | 10 mg/m2 per day PO, 0-7, 14-20 (0-20 for patients treated with 1 DI) | Dexamethasone | 10 mg/m2 per day PO, days 0-7, 14-20 (0-20 for patients treated with 1 DI) |
| Vincristine | 1.5 mg/m2 per day IV, days 0, 7, 14 | Vincristine | 1.5 mg/m2 per day IV, days 0, 7, 14 |
| Doxorubicin | 25 mg/m2 per day IV, days 0, 7, 14 | Doxorubicin | 25 mg/m2 per day IV, days 0, 7, 14 |
| Asparaginase | 6000 U/m2 per day IM, days 3, 5, 7, 10, 12, 14 | PEG asparaginase | 2500 IU/m2 per day IM, day 3 |
| Methotrexate* | IT, day 0 | Methotrexate* | IT day 0 |
| Reconsolidation (3 wk) | Reconsolidation (4 wk) | ||
| Cyclophosphamide | 1000 mg/m2 per day IV, day 28 | Cyclophosphamide | 1000 mg/m2 per day IV, day 28 |
| Thioguanine | 60 mg/m2 per day PO, days 28-41 | Thioguanine | 60 mg/m2 per day PO, days 28-41 |
| Cytarabine | 75 mg/m2 per day SQ or IV, days 29-32, 36-39 | Cytarabine | 75 mg/m2 per day SQ or IV, days 29-32, 36-39 |
| Methotrexate* | IT, days 28, 35 | Methotrexate* | IT days 28, 35 |
| — | Vincristine | 1.5 mg/m2 per day IV, days 42, 49 | |
| — | PEG asparaginase | 2500 U/m2 per day IM, day 42 | |
| — | Interim maintenance II (8 wk): same as Interim maintenance I | — | |
| — | Delayed intensification II (8 wk): same as Delayed intensification I | — | |
| Maintenance (12 wk)† | Maintenance (12 wk)† | ||
| Vincristine | 1.5 mg/m2 per day IV, days 0, 28, 56 | Same as standard maintenance | — |
| Prednisone | 40 mg/m2 per day PO, days 0-4, 28-32, 56-60 | — | — |
| Mercaptopurine | 75 mg/m2 per day PO, days 0-83 | — | — |
| Methotrexate | 20 mg/m2 per day PO, days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77 | — | — |
| Methotrexate* | IT day 0 (and 28 cycles 1-4 for patients receiving 1 DI and IM) | — | — |
| Standard therapy . | Increased intensity therapy . | ||
|---|---|---|---|
| Phase and treatment . | Dose . | Phase and treatment . | Dose . |
| Consolidation (5 wk) | Consolidation (9 wk) | ||
| Cyclophosphamide | 1000 mg/m2 per day IV, days 0, 14 | Cyclophosphamide | 1000 mg/m2 per day IV, days 0, 28 |
| Cytarabine | 75 mg/m2 per day IV, days 1-4, 8-11, 15-18, 22-25 | Cytarabine | 75 mg/m2 per day SQ IV, days 1-4, 8-11, 29-32, 36-39 |
| Mercaptopurine | 60 mg/m2 per day PO, days 0-27 | Mercaptopurine | 60 mg/m2 per day PO, days 0-13, 28-41 |
| Methotrexate* | IT, days 1, 8, 15, 22 | Methotrexate‡ | IT, days 1,8, 15, 22 |
| — | PEG asparaginase | 2500 U/m2 per day IM, days 14, 42 | |
| — | Vincristine | 1.5mg/m2 per day, days 14, 21, 42, 49 | |
| Interim maintenance (8 wk) | Interim maintenance I (7 wk) | ||
| Mercaptopurine | 60 mg/m2 per day PO, days 0-41 | Vincristine | 1.5 mg/m2 per day IV, days 0, 10, 20, 30, 40 |
| Methotrexate | 15 mg/m2 per day PO, days 0, 7, 14, 21, 28, 35 | Methotrexate | 100 mg/m2 per day IV, days 0, 10, 20, 30, 40 (escalate by 50 mg/m2 per dose) |
| — | PEG asparaginase | 2500 U/m2 per day IM, days 1, 21 | |
| Methotrexate* | IT days 0, 28 | Methotrexate* | IT days, 0. 30 |
| Delayed intensification (7 wk) | Delayed intensification (8 wk) | ||
| Reinduction (4 wk) | Reinduction (4 wk) | ||
| Dexamethasone | 10 mg/m2 per day PO, 0-7, 14-20 (0-20 for patients treated with 1 DI) | Dexamethasone | 10 mg/m2 per day PO, days 0-7, 14-20 (0-20 for patients treated with 1 DI) |
| Vincristine | 1.5 mg/m2 per day IV, days 0, 7, 14 | Vincristine | 1.5 mg/m2 per day IV, days 0, 7, 14 |
| Doxorubicin | 25 mg/m2 per day IV, days 0, 7, 14 | Doxorubicin | 25 mg/m2 per day IV, days 0, 7, 14 |
| Asparaginase | 6000 U/m2 per day IM, days 3, 5, 7, 10, 12, 14 | PEG asparaginase | 2500 IU/m2 per day IM, day 3 |
| Methotrexate* | IT, day 0 | Methotrexate* | IT day 0 |
| Reconsolidation (3 wk) | Reconsolidation (4 wk) | ||
| Cyclophosphamide | 1000 mg/m2 per day IV, day 28 | Cyclophosphamide | 1000 mg/m2 per day IV, day 28 |
| Thioguanine | 60 mg/m2 per day PO, days 28-41 | Thioguanine | 60 mg/m2 per day PO, days 28-41 |
| Cytarabine | 75 mg/m2 per day SQ or IV, days 29-32, 36-39 | Cytarabine | 75 mg/m2 per day SQ or IV, days 29-32, 36-39 |
| Methotrexate* | IT, days 28, 35 | Methotrexate* | IT days 28, 35 |
| — | Vincristine | 1.5 mg/m2 per day IV, days 42, 49 | |
| — | PEG asparaginase | 2500 U/m2 per day IM, day 42 | |
| — | Interim maintenance II (8 wk): same as Interim maintenance I | — | |
| — | Delayed intensification II (8 wk): same as Delayed intensification I | — | |
| Maintenance (12 wk)† | Maintenance (12 wk)† | ||
| Vincristine | 1.5 mg/m2 per day IV, days 0, 28, 56 | Same as standard maintenance | — |
| Prednisone | 40 mg/m2 per day PO, days 0-4, 28-32, 56-60 | — | — |
| Mercaptopurine | 75 mg/m2 per day PO, days 0-83 | — | — |
| Methotrexate | 20 mg/m2 per day PO, days 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 77 | — | — |
| Methotrexate* | IT day 0 (and 28 cycles 1-4 for patients receiving 1 DI and IM) | — | — |
IV indicates intravenously; PO, orally; IT, intrathecally; SQ, subcutaneously; IM, intramuscularly; and —, not applicable.
The doses were age-adjusted as follows: age 1 to 1.9 years, 8 mg; age 2 to 2.9 years, 10 mg; age > 3 years, 12 mg;
The cycles of maintenance therapy were repeated until the total duration of therapy, beginning with the first interim maintenance period, reached 2 years for girls and 3 years for boys.
During the first 2 weeks of consolidation therapy in the increased intensity PII regimen, patients with central nervous systems disease at diagnosis received 2400 cGy to the cranial midplane in 12 fractions and 600 cGy to the spinal cord in 3 fractions. Patients with testiculomegaly at diagnosis received 2400 cGy bilateral testicular radiation in 8 fractions during consolidation therapy. Patients with central nervous system disease at diagnosis did not receive intrathecal methotrexate on days 15 and 22 of consolidation therapy.