Outline of protocol NILG-ALL 09/00, MRD study, and treatment realization. Induction/consolidation (C indicates cycle; HD, high-dose cycle): pre-phase (T-ALL only): cyclophosphamide (CY) 300 mg/m² intravenously and prednisolone (PDN) 20 mg/m² twice a day intravenously or by mouth on days − 3 to 0. C1: idarubicin (IDR) 10 mg/m² intravenously on days 1 and 2; vincristine (VCR) 2 mg intravenously on days 1, 8, and 15; l-asparaginase (Erwinia) 6000 IU/m² intravenously on days 8, 10, 12, 14, 16, and 18; PDN 30 mg/m² twice a day intravenously or by mouth on days 1 to 7 and 20 mg/m² twice a day on days 8 to 15 (then tapered); G-CSF 5 μg/kg subcutaneously from day 4 to resolution of neutropenia less than 0.5 × 10⁹/L. C2, C3, C5, C6: IDR 12 mg/m² (10 mg/m² in C5-6) intravenously on days 1 and 2; VCR 2 mg intravenously on day 1; CY 750 mg/m² intravenously on day 2; dexamethasone (DXM) 4 mg twice a day intravenously or by mouth on days 1 to 4; G-CSF from day 4. HD4,7: Methotrexate (MTX) 1.5 g/m² intravenously on day 1 (20% in 1 hour, 80% over 23 hours); cytarabine (Ara-C) 2 g/m² twice a day intravenously on days 2 and 3 (1.2 g/m² if MTX plasma concentration > 25 mM); PDN 40 mg twice a day by mouth on days 1 to 3; folinic acid 15 mg/m² intravenously every 6 hours starting 24 hours from end of MTX to an MTX plasma concentration less than 0.1 mM; G-CSF from day 4. C8: IDR 6 mg/m² intravenously on days 1 and 8; VCR 1 mg/m² intravenously on days 1 and 8; PDN 20 mg/m² twice a day by mouth on days 1 to 15. Maintenance: CY 100 mg/m² by mouth on days 1 to 4 (months 1, 3, 5, 7, 9, 11); VCR 1 mg/m² intravenously on day 1; PDN 20 mg/m² twice a day by mouth on days 1 to 5 (months 2, 4, 6, 8, 10, 12); 6-mercaptopurine (6MP) 75 mg/m² by mouth on days 8 to 28 (months 1-12) and 1 to 28 (months 13-24); MTX 30 mg/weekly by mouth or intramuscularly (months 1-24). CNS prophylaxis: Intrathecal MTX 12.5 mg, Ara-C 50 mg, and PDN 40 mg on days 2 and 16 of C1; days 2 and 9 of C2; day 2 of C3, C5, C6, and C8; and day 1 of maintenance cycles 1, 3, 5, and 7, except if prior H/C(s). Hypercycles (H/C): H/C1, H/C3: etoposide (VP) 100 mg/m² twice a day intravenously and 6MP 225 mg/m² by mouth (in 3 divided doses) on days 1 to 4; melphalan (Mel) 100 mg/m² intravenously on day 5; autologous blood stem cell reinfusion on day 6 (1-2 × 10⁶/kg CD34⁺ cells); G-CSF from day 7. H/C2, H/C4: MTX 1.5 g/m² intravenously on day 1; Ara-C 3 g/m² twice a day intravenously on days 2 to 4 (2 g/m² if MTX plasma concentration > 25 mM); folinic acid rescue starting 24 hours from end of MTX, autologous blood stem cell rein fusion on day 6, and G-CSF from day 7. If CD20⁺ ALL: rituximab 375 mg/m² intravenously on day 10 of each H/C. Dose reductions in patients older than 59 years: CY 75 mg/m² (pre-phase), 500 mg/m² (C2-3, C5-6), omitted (maintenance); IDR 8 mg/m² (C1-3) and 6 mg/m² (C5-6, C8); VCR 1 mg/m² (C1-3, C5-6, C8), omitted (maintenance); ASP 6000 IU total dose; PDN 20 mg/m² twice a day (C1, C8), omitted (maintenance); DXM omitted; VP 75 mg/m² twice a day (H/C1); 6MP 150 mg/m² (H/C1); ML 70 mg/m² (H/C1); MTX 1 g/m² (HD4,7, H/C2); Ara-C 1.2 g/m² twice a day (C4,7, H/C2); intrathecal MTX 10 mg, Ara-C 40 mg (CNS prophylaxis). Imatinib mesylate (600 mg/d orally) was added in January 2003 in patients with Ph⁺ ALL, on days 15 to 21 of C1, days − 3 to 4 of C2 to C8, days 1 to 7 of each H/C, and long term during maintenance.