Figure 1.
Scheme of treatment and bone marrow sampling time points. (A) Schematic representation of GMALL 06/99 SR first-year treatment. (B) Bone marrow sampling time-points in the GMALL 06/99 trial. (C) Bone marrow sampling time-points in the GMALL 05/93 MRD pilot trial (time-points synchronized according to the treatment phase). ADR indicates adriamycine; CP, cyclophosphamide; DEXA, dexamethasone; DNR, daunorubicine; (HD)-ARAC, (high-dose) cytarabine; (HD)-MTX, (high-dose) methotrexate; 6MP, mercaptopurine; PEG-ASP, PEG-asparaginase; PRED, prednisolone; TG, thioguanine; VCR, vincristine; VDS, vindesine; VM26, tenisposide; and VP16, etoposide. Specifics of drugs and doses used in the main GMALL 06/99 treatment protocol. Induction I (including preinduction treatment): 10 mg/m2 DEXA orally on days 1-5, 11-14; 200 mg/m2 CP intravenously on days 1-3 (CP part of Induction I protocol only until 2000); 1000 U/m2 PEG-ASP intravenously on day 18 (reduced dose intensity in patients older than 55 years); 2 mg VCR intravenously on days 4, 11, and 18; 45 mg/m2 DNR intravenously on days 4, 5, 11, and 12 (reduced dose intensity in patients older than 55 years); and 15 mg MTX intrathecally on day 1. Induction II: 1000 mg/m2 CP intravenously on days 1 and 21; 75 mg/m2 ARAC intravenously on days 3-6, 10-13, and 17-20; 60 mg/m2 6MP orally on days 1-21; 15 mg MTX intrathecally on days 3, 10, and 17. Consolidation I: 10 mg/m2 DEXA orally on days 1-5; 3 mg/m2 VDS intravenously on day 1; 1500 mg/m2 HD-MTX intravenously on day 1; 250 mg/m2 VP16 intravenously on days 4 and 5; and 2 × 2000 mg/m2 HD-ARAC intravenously on day 5. Consolidation II: 1500 mg/m2 HD-MTX intravenously on days 1 and 15; 500 U/m2 PEG-ASP intravenously on days 2 and 16; and 60 mg/m2 6MP orally on days 1-7 and 15-21. Reinduction I and II: 3 × 20 mg/m2 PRED orally on days 1-14; 3 mg/m2 VDS intravenously on days 1 and 7; 50 mg/m2 ADR intravenously on days 1 and 7; intrathecal triple chemotherapy with 15 mg MTX, 40 mg ARAC, and 4 mg DEXA intrathecally on days 1 and 15; 1000 mg/m2 CP intravenously on day 15; 75 mg/m2 ARAC intravenously on days 17-20, 24-27; and 60 mg/m2 TG orally on days 15-28. Consolidation III: see Consolidation II. Consolidation IV: 150 mg/m2 ARAC intravenously on days 1-5; 100 mg/m2 VM26 intravenously on days 1-5; and intrathecal triple therapy (see Reinduction) on day 1. Consolidation V: 1000 mg/m2 CP intravenously on day 1; 500 mg/m2 ARAC intravenously on day 1; intrathecal triple therapy (see Reinduction) on day 1. Consolidation VI: see Consolidation II; and intrathecal triple therapy (see Reinduction I) at week 52.

Scheme of treatment and bone marrow sampling time points. (A) Schematic representation of GMALL 06/99 SR first-year treatment. (B) Bone marrow sampling time-points in the GMALL 06/99 trial. (C) Bone marrow sampling time-points in the GMALL 05/93 MRD pilot trial (time-points synchronized according to the treatment phase). ADR indicates adriamycine; CP, cyclophosphamide; DEXA, dexamethasone; DNR, daunorubicine; (HD)-ARAC, (high-dose) cytarabine; (HD)-MTX, (high-dose) methotrexate; 6MP, mercaptopurine; PEG-ASP, PEG-asparaginase; PRED, prednisolone; TG, thioguanine; VCR, vincristine; VDS, vindesine; VM26, tenisposide; and VP16, etoposide. Specifics of drugs and doses used in the main GMALL 06/99 treatment protocol. Induction I (including preinduction treatment): 10 mg/m2 DEXA orally on days 1-5, 11-14; 200 mg/m2 CP intravenously on days 1-3 (CP part of Induction I protocol only until 2000); 1000 U/m2 PEG-ASP intravenously on day 18 (reduced dose intensity in patients older than 55 years); 2 mg VCR intravenously on days 4, 11, and 18; 45 mg/m2 DNR intravenously on days 4, 5, 11, and 12 (reduced dose intensity in patients older than 55 years); and 15 mg MTX intrathecally on day 1. Induction II: 1000 mg/m2 CP intravenously on days 1 and 21; 75 mg/m2 ARAC intravenously on days 3-6, 10-13, and 17-20; 60 mg/m2 6MP orally on days 1-21; 15 mg MTX intrathecally on days 3, 10, and 17. Consolidation I: 10 mg/m2 DEXA orally on days 1-5; 3 mg/m2 VDS intravenously on day 1; 1500 mg/m2 HD-MTX intravenously on day 1; 250 mg/m2 VP16 intravenously on days 4 and 5; and 2 × 2000 mg/m2 HD-ARAC intravenously on day 5. Consolidation II: 1500 mg/m2 HD-MTX intravenously on days 1 and 15; 500 U/m2 PEG-ASP intravenously on days 2 and 16; and 60 mg/m2 6MP orally on days 1-7 and 15-21. Reinduction I and II: 3 × 20 mg/m2 PRED orally on days 1-14; 3 mg/m2 VDS intravenously on days 1 and 7; 50 mg/m2 ADR intravenously on days 1 and 7; intrathecal triple chemotherapy with 15 mg MTX, 40 mg ARAC, and 4 mg DEXA intrathecally on days 1 and 15; 1000 mg/m2 CP intravenously on day 15; 75 mg/m2 ARAC intravenously on days 17-20, 24-27; and 60 mg/m2 TG orally on days 15-28. Consolidation III: see Consolidation II. Consolidation IV: 150 mg/m2 ARAC intravenously on days 1-5; 100 mg/m2 VM26 intravenously on days 1-5; and intrathecal triple therapy (see Reinduction) on day 1. Consolidation V: 1000 mg/m2 CP intravenously on day 1; 500 mg/m2 ARAC intravenously on day 1; intrathecal triple therapy (see Reinduction) on day 1. Consolidation VI: see Consolidation II; and intrathecal triple therapy (see Reinduction I) at week 52.

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