Table 1.
Summary of studies included in meta-analysis.
| Study | Design | Period | Entry Criteria | Size | Age (years) | Induction Therapy | CR (%) | Single Ara-C dose | Cumulative Ara-C dose | Medium follow-up (Month) | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| HDAraC vs IDAraC | |||||||||||
| MRC AML15 | Openflabel, multicenter phase III | 2002–2009 | Primary or secondary AML including MDS; no pregnancy; aged 15–60 years | 329/328 | 48 (15–69) | DA or ADE or FLAG-Ida × 1–2 | 78–82 | (3 g/m2 every 12 h on days 1, 3, 5) × 2 vs (1.5 g/m2 every 12 h on days 1, 3, 5) × 2 | 36 g vs 18 g | 67 (2.4–114) | |
| SAL AML2003 | Open-label, multicenter phase III | 2003–2009 | Primary or secondary AML, or refractory anemia with excess blasts (RAEB2); aged 16–60 years | 251/254 | 47 (18–60) | DA × 2 | 65 | (3 g/m2 every 12 h on days 1, 3, 5) × 3 vs (1 g/m2 every 12 h on days 1–5/6) × 2 | 54 g vs 20–22 g | NR | |
| SAL AML96 | Open-label, multicenter phase IV | 1996–2003 | Primary or secondary AML; aged 15–64 years | 363/382 | 47 (15–60) | MAV-MAMAC × 1 | 66 | (3 g/m2 every 12 h on days 1–6) × 1 vs (1 g/m2 every 12 h on days 1–6) × 1 | 36 g vs 12 g | 99.6 (NR) | |
| IDAraC vs LDAraC | |||||||||||
| SWOG 8601 | Open-label, multicenter phase III | 1986–1993 | Primary AML; no MDS; aged < 65 years; | 78/53 | 45 (15–60) | DA | 58 | (2 g/m2 every 12 h on days 1–5) × 1 vs (0.2 g/m2/d on days 1–7) × 2 | 20 g vs 2.8 g | 51 (NR) | |
| JALSG AML201 | Open-label, multicenter phase III | 2001–2005 | Primary AML with enough function of major organs; no MDS; aged 15–64 years | 389/392 | 47 (15–64) | DA or AI × 1–2 | 78 | (2 g/m2 every 12 h on days 1–5) × 3 vs (0.2 g/m2/d on days 1–5) × 4 | 60 g vs 4 g | 48 (5–78) | |
| EORTC & GIMEMA AML8B | Open-label, multicenter phase III | 1986–1993 | Primary AML; no APL; absence of irreversible major organ failure; aged 46–60 | 158/157 | NR (46–60) | DA × 1–2 | 61 | (0.5 g/m2 every 12 h on days 1–6) × 1 + (2 g/m2 every 12 h on days 1–4) × 1 vs (0.2 g/m2/d on days 1–7) × 1 | 22 g vs 1.4 g | 225 (NR) | |
| HDAraC vs LDAraC | |||||||||||
| SAKK 1985 | Open-label, multicenter phase III | 1985–1992 | Primary AML (FAB Ml-6); aged 15–65 years | 70/67 | 45 (16–61) | DA × 1 + (Amsacrine + VP-16) × 1 | 61 | (3 g/m2 every 12 h on days 1–6) × 1 vs (0.1 g/m2/d on days 1–7) × 1 | 36 g vs 0.7 g | 72 (NR) | |
| CALGB 8525 | Open-label, multicenter phase III | 1985–1990 | Primary AML; no prior MDS, uncontrolled infection; aged 16–86 years | 187/206/203 | 52 (16–86) | DA × 1–2 | 64 | (3 g/m2 every 12 h on days 1, 3, 5) × 4 vs (0.4 g/m2/d on days 1–5) × 4 | 72 g vs 8 g vs 2 g | 52 (NR) | |
| ALFA 9802 | Open-label, multicenter phase III | 1999–2006 | Primary AML; no APL; absence of irreversible major organ failure; aged 15–50 years | 117/120 | 46 (17–50) | DA–MTZA × 1 | 89 | (3 g/m2 every 12 h on days 1, 3, 5) × 4 vs (0.5 mg/m2/d on days 1–3) × 2 | 72 g vs 3 g | 60 (NR) | |
| ALLG M7 | Open-label, multicenter phase III | 1995–2000 | Primary AML; absence of irreversible major organ failure; aged 15–60 years | 99/103 | 41 (15–60) | High-dose Ara-C + IA + VP-16 × 1–2 | 80 | (3 g/m2 every 12 h on days 1, 3, 5, 7) × 1 vs (0.1 g/m2/d on days 1–5) × 2 | 24 g vs 0.5 g | 45 (NR) | |
MRC, Medical Research Council; SAL, Study Alliance Leukemia; EORTC, European Organization for Research and Treatment of Cancer; GIMEMA, Gruppo Italiano Malattie Ematologiche Maligne dell’Adulto; JALSG, Japan Adult Leukemia Study; Group CALGB, Cancer and Leukemia Group B; ALFA, Acute Leukemia French Association; ALLG, Australasian Leukaemia and Lymphoma Group; AML, acute myeloid leukemia; MDS, myelodysplastic syndromes; Ara-C, cytarabine; DA, daunorubicin and cytarabine; ADE, cytarabine, daunorubicin, and etoposide; FLAG-Ida, fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin; MAV–MAMAC, mitoxantrone, standard-dose cytarabine, etoposide – intermediate-dose cytarabine, amsacrine; AI: cytarabine, idarubicin; MTZA, mitoxantrone, cytarabine; IA, idarubicin; VP–16, etoposide; NR, not reported.