Efficacy and safety of different doses of cytarabine in consolidation therapy for adult acute myeloid leukemia patients: a network meta-analysis.

Cytarabine (Ara-C) in consolidation therapy played important role in preventing relapses for AML patients achieved complete remission, but the optimum dose remains elusive. In this network meta-analysis, we compared benefit and safety of high-, intermediate- and low-dose Ara-C [HDAraC (>2 g/m, ≤3 g/m twice daily), IDAraC (≥1 g/m, ≤2 g/m twice daily) and LDAraC (<1 g/m twice day)] in consolidation, based on ten randomized phase III/IV trials from 1994 to 2016, which included 4008 adult AML patients. According to the results, HDAraC in a dosage of 3 g/m twice daily significantly improved disease-free survival (DFS) compared with IDAraC [hazard rate (HR) 0.87, 95% CrI 0.79-0.97) and LDAraC (HR 0.86, 95% CrI 0.78-0.95). Subgroup analysis further showed that the DFS advantage of HDAraC is focused on the patients with favorable cytogenetics, but not the other cytogenetics. Compared with LDAraC, HDAraC (HR 6.04, 95% CrI 1.67-21.49) and IDAraC (HR 3.80, 95% CrI 1.05-12.85) were associated with higher risk of grade 3-4 non-haematological toxicity. However, no significant difference between HDAraC and IDAraC was found. These findings suggest that Ara-C in a dosage of 3 g/m twice daily provides maximal anti-relapse effect.