Treatment protocols
| Treatment element/drug . | Single or daily dose . | Days given . |
|---|---|---|
| Induction | ||
| Protocol I | ||
| Phase A | ||
| Prednisone (orally) | 60 mg/m2 per day | 1-28† |
| Vincristine (IV) | 1.5 mg/m2 (max, 2 mg) | 8, 15, 22, 29 |
| Daunorubicin (IV) | 30 mg/m2 | 8, 15, 22, 29 |
| l-Asparaginase (IV) | 10 000 IU/m2 | 12, 15, 18, 21, 24, 27, 30†, 33† |
| Methotrexate (IT) | 12 mg‡ | 1, 15, 29 |
| Phase B (only in SRG and MRG) | ||
| Cyclophosphamide (IV) | 1000 mg/m2 | 36, 64 |
| Cytarabine (IV) | 75 mg/m2 per day | 38-41, 45-48, 52-55, 59-62 |
| 6-Mercaptopurine (orally) | 60 mg/m2 per day | 36-64 |
| Methotrexate (IT) | 12 mg‡ | 45, 59 |
| Consolidation (in SRG and MRG) | ||
| Protocol M | ||
| 6-Mercaptopurine (orally) | 25 mg/m2 per day | 1-56 |
| Methotrexate (24-hr inf)1-153 | 5 g/m2 | 8, 22, 36, 50 |
| Methotrexate (IT) | 12 mg‡ | 8, 22, 36, 50 |
| Protocol M-A1-154 | ||
| l-Asparaginase (IM) | 25 000 IU/m2 | 10, 24, 38, 52 |
| Reinduction (in SRG and MRG) | ||
| Protocol II | ||
| Dexamethasone (orally) | 10 mg/m2 per day | 1-21 |
| Vincristine (IV) | 1.5 mg/m2 (max, 2 mg) | 8, 15, 22, 29 |
| Doxorubicin (IV) | 30 mg/m2 | 8, 15, 22, 29 |
| l-Asparaginase (IV) | 10 000 IU/m2 | 8, 11, 15, 18 |
| Cyclophosphamide (IV) | 1000 mg/m2 | 36 |
| Cytarabine (IV) | 75 mg/m2 | 38-41, 45-48 |
| 6-Thioguanine (orally) | 60 mg/m2 | 36-49 |
| Methotrexate (IT) | 12 mg‡ | 38, 45 |
| Intensive reconsolidation (HRG only) | ||
| Element HR-1 | ||
| Dexamethasone (orally) | 20 mg/m2 | 1-5 |
| 6-Mercaptopurine (orally) | 100 mg/m2 per day | 1-5 |
| Vincristine (IV) | 1.5 mg/m2 | 1, 5 |
| Methotrexate (24-hr inf)1-153 | 5 g/m2 | 1 |
| Cytarabine (3-hr inf) | 2 g/m2 (single dose) | 5 (twice, 12-hr interval) |
| l-Asparaginase (IM) | 25 000 IU/m2 | 6 |
| Methotrexate/cytarabine/ prednisolone (IT) | 12 mg/30 mg/10 mg‡ | 1 |
| Element HR-2 | ||
| Dexamethasone (orally) | 20 mg/m2 | 1-5 |
| Thioguanine (orally) | 100 mg/m2 per day | 1-5 |
| Vindesine (IV) | 3 mg/m2 | 1 |
| Methotrexate (24-hr inf)1-153 | 5 g/m2 | 1 |
| Ifosfamide (1-hr inf) | 400 mg/m2 per day | 1-5 |
| Daunorubicin (24-hr inf) | 50 mg/m2 | 5 |
| l-Asparaginase (IM) | 25 000 IU/m2 | 6 |
| Methotrexate/cytarabine/ prednisolone (IT) | 12 mg/30 mg/10 mg‡ | 1 |
| Element HR-3 | ||
| Dexamethasone (orally) | 20 mg/m2 | 1-5 |
| Cytarabine (3-hr inf) | 2 g/m2 (single dose) | 1, 2 (4 times, 12-hr interval) |
| Etoposide (1-hr inf) | 150 mg/m2 per day | 3-5 |
| l-Asparaginase (IM) | 25 000 IU/m2 | 6 |
| Methotrexate/cytarabine/ prednisolone (IT) | 12 mg/30 mg/10 mg‡ | 5 |
| Treatment element/drug . | Single or daily dose . | Days given . |
|---|---|---|
| Induction | ||
| Protocol I | ||
| Phase A | ||
| Prednisone (orally) | 60 mg/m2 per day | 1-28† |
| Vincristine (IV) | 1.5 mg/m2 (max, 2 mg) | 8, 15, 22, 29 |
| Daunorubicin (IV) | 30 mg/m2 | 8, 15, 22, 29 |
| l-Asparaginase (IV) | 10 000 IU/m2 | 12, 15, 18, 21, 24, 27, 30†, 33† |
| Methotrexate (IT) | 12 mg‡ | 1, 15, 29 |
| Phase B (only in SRG and MRG) | ||
| Cyclophosphamide (IV) | 1000 mg/m2 | 36, 64 |
| Cytarabine (IV) | 75 mg/m2 per day | 38-41, 45-48, 52-55, 59-62 |
| 6-Mercaptopurine (orally) | 60 mg/m2 per day | 36-64 |
| Methotrexate (IT) | 12 mg‡ | 45, 59 |
| Consolidation (in SRG and MRG) | ||
| Protocol M | ||
| 6-Mercaptopurine (orally) | 25 mg/m2 per day | 1-56 |
| Methotrexate (24-hr inf)1-153 | 5 g/m2 | 8, 22, 36, 50 |
| Methotrexate (IT) | 12 mg‡ | 8, 22, 36, 50 |
| Protocol M-A1-154 | ||
| l-Asparaginase (IM) | 25 000 IU/m2 | 10, 24, 38, 52 |
| Reinduction (in SRG and MRG) | ||
| Protocol II | ||
| Dexamethasone (orally) | 10 mg/m2 per day | 1-21 |
| Vincristine (IV) | 1.5 mg/m2 (max, 2 mg) | 8, 15, 22, 29 |
| Doxorubicin (IV) | 30 mg/m2 | 8, 15, 22, 29 |
| l-Asparaginase (IV) | 10 000 IU/m2 | 8, 11, 15, 18 |
| Cyclophosphamide (IV) | 1000 mg/m2 | 36 |
| Cytarabine (IV) | 75 mg/m2 | 38-41, 45-48 |
| 6-Thioguanine (orally) | 60 mg/m2 | 36-49 |
| Methotrexate (IT) | 12 mg‡ | 38, 45 |
| Intensive reconsolidation (HRG only) | ||
| Element HR-1 | ||
| Dexamethasone (orally) | 20 mg/m2 | 1-5 |
| 6-Mercaptopurine (orally) | 100 mg/m2 per day | 1-5 |
| Vincristine (IV) | 1.5 mg/m2 | 1, 5 |
| Methotrexate (24-hr inf)1-153 | 5 g/m2 | 1 |
| Cytarabine (3-hr inf) | 2 g/m2 (single dose) | 5 (twice, 12-hr interval) |
| l-Asparaginase (IM) | 25 000 IU/m2 | 6 |
| Methotrexate/cytarabine/ prednisolone (IT) | 12 mg/30 mg/10 mg‡ | 1 |
| Element HR-2 | ||
| Dexamethasone (orally) | 20 mg/m2 | 1-5 |
| Thioguanine (orally) | 100 mg/m2 per day | 1-5 |
| Vindesine (IV) | 3 mg/m2 | 1 |
| Methotrexate (24-hr inf)1-153 | 5 g/m2 | 1 |
| Ifosfamide (1-hr inf) | 400 mg/m2 per day | 1-5 |
| Daunorubicin (24-hr inf) | 50 mg/m2 | 5 |
| l-Asparaginase (IM) | 25 000 IU/m2 | 6 |
| Methotrexate/cytarabine/ prednisolone (IT) | 12 mg/30 mg/10 mg‡ | 1 |
| Element HR-3 | ||
| Dexamethasone (orally) | 20 mg/m2 | 1-5 |
| Cytarabine (3-hr inf) | 2 g/m2 (single dose) | 1, 2 (4 times, 12-hr interval) |
| Etoposide (1-hr inf) | 150 mg/m2 per day | 3-5 |
| l-Asparaginase (IM) | 25 000 IU/m2 | 6 |
| Methotrexate/cytarabine/ prednisolone (IT) | 12 mg/30 mg/10 mg‡ | 5 |
IV indicates intravenous; max, maximum; IT, intrathecal; SRG, standard-risk group; MRG, middle-risk group; inf, infusion; IM, intramuscular; and HRG, high-risk group.
For induction, consolidation, and reinduction, the days given are the chronologic days of treatment; adjustments in time schedules were allowed if clinical condition and marrow recovery were inadequate (according to protocol guidelines). For intensive reconsolidation, the days given are the number of days of application per element; each element was given 3 times unless otherwise indicated.
In the HRG, protocol I phase A had only 21 days of prednisone therapy and 6 doses of l-asparaginase.
Doses were adjusted for children under 3 years of age.
Given with IV citrovorum factor rescue starting at hour 42 with 30 mg/m2 (or 15 mg/m2, see text) and with 2 more doses given at hour 48 and hour 54, respectively (each 15 mg/m2).
Only MRG patients randomly assigned to M-A received additional l-asparaginase (4 doses starting 54 hours after starting high-dose MTX during consolidation.