Induction | Vincristine 1·5 mg/m2 i.v. days 1, 7, 14, 21 |
Weeks 1-4 | Prednisolone 40 mg/m2 p.o. days 1-28 |
 | L-Asparaginase 6000 U/m2 s.c./i.m. t.i.w. nine doses |
 | IT MTX days 1, 8 |
Intensification | Vincristine 1·5 mg/m2 i.v. day 1 |
Weeks 5-7 | Prednisolone 40 mg/m2 p.o. days 1-7 then 7 d taper |
 | Etoposide 100 mg/m2 i.v. days 1-5 |
 | Cytarabine 100 mg/m2 i.v. given 12 hourly days 1-5 |
 | Daunorubicin 45 mg/m2 days 1, 2 |
 | Thioguanine 80 mg/m2 p.o. days 1-5 |
 | IT MTX day 1 |
Intensification | Vincristine 1·5 mg/m2 i.v. day 1 |
Weeks 20-22 | Prednisolone 40 mg/m2 p.o. days 1-5 |
 | Etoposide 100 mg/m2 i.v. days 1-5 |
 | Cytarabine 100 mg/m2 i.v. given 12 hourly days 1-5 |
 | Daunorubicin 45 mg/m2 days 1, 2 |
 | Thioguanine 80 mg/m2 p.o. days 1-5 |
 | IT MTX day 1 |
CNS-directed treatment weeks 8-19: Randomization WBC ≤ 50 × 109/l | IT MTX weekly (weeks 9-12) or HDM 6 g/m2 (≥ 4 years old) or 8 g/m2 (< 4 years old) weeks 9, 11, 13 + IT MTX weeks 9, 11, 13, 14. HDM IV over 24 hours, folinic acid rescue commenced at 36 hours from start at 15 g/m2 3-hourly, reduced to 15 g/m2 6-hourly once serum MTX level < 2 × 106 mol/l and stopped once serum MTX level below 1 × 107 mol/l. |
CNS-directed treatment weeks 8-19: Randomization WBC ≥ 50 × 109/l | HDM + IT MTX as above or 24 Gy cranial radiotherapy in 15 fractions of 1·6 Gy each in weeks 9-12 (except children of 1-2 years age who were allocated HDM) |
 | Plus IT MTX weeks 9-11 |
Interim continuation therapy | Mercaptopurine 75 mg/m2 p.o. daily |
Weeks 8-19 | Methotrexate 20 mg/m2 p.o. weekly except when ITMTX given |
and 23-34 | Vincristine 1·5 mg/m2 i.v. every 4 weeks |
 | Prednisolone 40 mg/m2 p.o. daily × 5 d every 4 weeks. |
Continuation therapy Weeks | Same as above ± 3-monthly ITMTX |
35 or 43-100 | Age-adjusted |
Third intensification Weeks 35-42 | Dexamethasone 10 mg/m2 p.o. for 10 d then 4 d taper |
 | Vincristine 1·5 mg/m2 i.v. days 1, 7, 14, 21 |
 | L-Asparaginase 6000 U/m2 s.c./i.m. t.i.w. nine doses |
 | IT MTX (age-adjusted) days 1, 28 |
 | Cyclophosphamide 600 mg/m2 i.v. days 28, 42 |
 | Cytarabine 75 mg/m2 i.v./s.c. days 28-31, 35-38, 42-45, 49-52 |
 | Thioguanine 60 mg/m2 p.o. days 28-56 |