Dataset Information

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

ABSTRACT: 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/m², ?3?g/m² twice daily), IDAraC (?1?g/m², ?2?g/m² twice daily) and LDAraC (<1?g/m² 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/m² 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/m² twice daily provides maximal anti-relapse effect.

SUBMITTER: Wu D

PROVIDER: S-EPMC5572788 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Wu Di D Duan Chongyang C Chen Liyong L Chen Size S

Scientific reports 20170825 1

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/m2, ≤3 g/m2 twice daily), IDAraC (≥1 g/m2, ≤2 g/m2 twice daily) and LDAraC (<1 g/m2 twice day)] in consolidation, based on ten randomized phase III/IV tr ...[more]

PMID: 28842676

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Project description:ObjectiveWe aimed to retrospectively discern the heterogeneity of outcomes from clinicopathological characteristics and next-generation sequencing (NGS) data in adult patients with NPM1-mutated (NPM1mut ) acute myeloid leukemia (AML) induced with standard-dose (SD, 100-200 mg/m2 ) and intermediate-dose (ID, 1000-2000 mg/m2 ) cytarabine arabinose (Ara-C).MethodsIn the entire cohort and FLT3-ITD subgroups, multivariate Logistic and Cox regression analyses were used to analyze the comprehensive complete remission (cCR) rate after one or two induction cycles, event-free survival (EFS), and overall survival (OS).ResultsAmong a total of 203 NPM1mut patients evaluable for clinical outcome, 144 (70.9%) received a first SD-Ara-C induction and 59 (29.1%) received ID-Ara-C induction. Early death was recorded in seven (3.4%) after one or two cycles of induction. Focusing analysis on the NPM1mut /FLT3-ITD(-) subgroup, independent factors showing inferior outcome were presence of TET2 mutation [cCR rate, OR = 12.82 (95%CI 1.93-85.28), p = 0.008; EFS, HR = 2.92 (95%CI 1.46-5.86), p = 0.003], increasing age [EFS, HR = 1.49 (95%CI 1.10-2.02), p = 0.012 by every 10-years elevation], white blood cell count ≥60 × 109 /L [EFS, HR = 3.30 (95%CI 1.63-6.70), p = 0.001], and ≥4 mutated genes at initial diagnosis [OS, HR = 5.54 (95%CI 1.77-17.33), p = 0.003]. In contrast, when focusing on the NPM1mut /FLT3-ITD(+) subgroup, factors showing superior outcome were ID-Ara-C induction [cCR rate, OR = 0.20 (95%CI 0.05-0.81), p = 0.025; EFS, HR = 0.27 (95%CI 0.13-0.60), p = 0.001] and allo-transplantation [OS, HR = 0.45 (95%CI 0.21-0.94), p = 0.033]. Factors showing inferior outcome included CD34(+) [cCR rate, OR = 6.22 (95%CI 1.86-20.77), p = 0.003; EFS, HR = 2.01 (95%CI 1.12-3.61), p = 0.020] and ≥5 mutated genes [OS, HR = 2.85 (95%CI 1.33-6.10), p = 0.007].ConclusionWe conclude that TET2(+) , age, and white blood cell count convey an outcome risk modulation for AML with NPM1mut /FLT3-ITD(-) , as does CD34 and ID-Ara-C induction for NPM1mut /FLT3-ITD(+) . The findings permit re-stratification of NPM1mut AML into distinct prognostic subsets to guide risk-adapted individualized treatment.

Dataset Information

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

Publications

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

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