Treatment regimen
| Treatment regimen . |
|---|
| Induction, weeks 1-6 |
| Vincristine 1.5 mg/m2 IVP weekly × 4, days 1, 8, 15, 22 |
| Prednisone 40 mg/m2/d × 21 days, days 1-22 then stop |
| Doxorubicin 30 mg/m2 IV × 2, days 1 and 2* |
| (Randomized ± dexrazoxane as cardioprotectant) |
| Methotrexate 40 mg/m2 × 1, day 2 (8-24 hours after dox) |
| Triple intrathecal drugs × 4, days 1, (8), 15, 22, 29, and 36† |
| Doxorubicin 30 mg/m2 × 1, day 22* |
| ± HDM per randomized assignment, day 22‡ |
| Mercaptopurine 50 mg/m2/d PO × 14 days, days 22-36 |
| Consolidation, weeks 7-33 |
| 3-week cycles (start day 43) |
| Vincristine 2.0 mg/m2 IVP q3 weeks |
| Prednisone 120 mg/m2/d PO × 5 days |
| Doxorubicin 30 mg/m2 IV q3 weeks *(to a total of 360 mg/m2) |
| Mercaptopurine 50 mg/m2/d PO × 14 days |
| Asparaginase 25 000 IU/m2 IM weekly × 20 doses |
| Triple intrathecal drugs, weeks 10, (16), 22 |
| ± HDM per randomized assignment, weeks 7, 10, and 13‡ |
| CNS prophylaxis (for all patients) |
| Cranial radiation 1800 cGy in 9 fractions, start week 22 |
| Triple intrathecal drugs (doses by age) × 11 doses† |
| (CNS-2 and -3 received 2 additional doses, day 8 of induction and week [16] of consolidation) |
| Continuation, weeks 34-108 (repeat 3-week cycle until 2 years from date of documented complete remission) |
| 3-week cycles |
| Vincristine 2.0 mg/m2 IVP q3 weeks |
| Prednisone 120 mg/m2/d PO × 5 days |
| Methotrexate 30 mg/m2 IV/IM weekly |
| Mercaptopurine 50 mg/m2/d PO × 14 days |
| Triple intrathecal drugs, weeks 40, 58, 76, and 94† |
| Randomizations, at enrollment |
| Standard therapy ± dexrazoxane ± HDM |
| Start leucovorin rescue 75 mg/m2 at hour 36 then 15 mg/m2 q6 hours at hours 42, 48, 54, 60, 66, and 72, and until serum methotrexate level ≤ 0.1μM§ |
| Treatment regimen . |
|---|
| Induction, weeks 1-6 |
| Vincristine 1.5 mg/m2 IVP weekly × 4, days 1, 8, 15, 22 |
| Prednisone 40 mg/m2/d × 21 days, days 1-22 then stop |
| Doxorubicin 30 mg/m2 IV × 2, days 1 and 2* |
| (Randomized ± dexrazoxane as cardioprotectant) |
| Methotrexate 40 mg/m2 × 1, day 2 (8-24 hours after dox) |
| Triple intrathecal drugs × 4, days 1, (8), 15, 22, 29, and 36† |
| Doxorubicin 30 mg/m2 × 1, day 22* |
| ± HDM per randomized assignment, day 22‡ |
| Mercaptopurine 50 mg/m2/d PO × 14 days, days 22-36 |
| Consolidation, weeks 7-33 |
| 3-week cycles (start day 43) |
| Vincristine 2.0 mg/m2 IVP q3 weeks |
| Prednisone 120 mg/m2/d PO × 5 days |
| Doxorubicin 30 mg/m2 IV q3 weeks *(to a total of 360 mg/m2) |
| Mercaptopurine 50 mg/m2/d PO × 14 days |
| Asparaginase 25 000 IU/m2 IM weekly × 20 doses |
| Triple intrathecal drugs, weeks 10, (16), 22 |
| ± HDM per randomized assignment, weeks 7, 10, and 13‡ |
| CNS prophylaxis (for all patients) |
| Cranial radiation 1800 cGy in 9 fractions, start week 22 |
| Triple intrathecal drugs (doses by age) × 11 doses† |
| (CNS-2 and -3 received 2 additional doses, day 8 of induction and week [16] of consolidation) |
| Continuation, weeks 34-108 (repeat 3-week cycle until 2 years from date of documented complete remission) |
| 3-week cycles |
| Vincristine 2.0 mg/m2 IVP q3 weeks |
| Prednisone 120 mg/m2/d PO × 5 days |
| Methotrexate 30 mg/m2 IV/IM weekly |
| Mercaptopurine 50 mg/m2/d PO × 14 days |
| Triple intrathecal drugs, weeks 40, 58, 76, and 94† |
| Randomizations, at enrollment |
| Standard therapy ± dexrazoxane ± HDM |
| Start leucovorin rescue 75 mg/m2 at hour 36 then 15 mg/m2 q6 hours at hours 42, 48, 54, 60, 66, and 72, and until serum methotrexate level ≤ 0.1μM§ |
Maximum dosage recommendations: vincristine 2 mg/dose; doxorubicin 60 mg/dose; dexrazoxane 600 mg/dose; HDM 10 g/24-hour infusion; prednisone 80 mg/d during induction and 240 mg/d during consolidation and continuation; mercaptopurine 100 mg/d all phases; and methotrexate 80 mg/dose day 2 of induction and continuation.
IVP indicates intravenous push; dox, doxorubicin; HDM, high-dose methotrexate; q, every; and PO, orally.
Dexrazoxane 300 mg/m2 IV immediately before each dose of doxorubicin.
August 1999, protocol amended intrathecal drugs to cytarabine alone on induction days 1, (8), and 15. Doses on weeks 5 and 6 were omitted. All other intrathecal doses were methotrexate/cytarabine given weeks 4, 7, 10, (16), 22, 40, 58, 76, and 94.
HDM = Methotrexate 5 g/m2 IV infusion as a bolus of 0.5 gm/m2 over 0.5 hours then 4.5 g/m2 over 23.5 hours
Prior to March 1997, the hour-36 leucovorin dose was 15 mg/m2, repeated every 6 hours × 5 doses minimum. If the 72-hour serum MTX level was > 0.1μM, then leucovorin continued at 5 mg/m2 every 6 hours until the MTX level was < 0.1μM.