RESEARCH ARTICLE
High Doses of Daunorubicin during Induction Therapy of Newly Diagnosed Acute Myeloid Leukemia: A Systematic Review and MetaAnalysis of Prospective Clinical Trials Qiang Gong, Lixin Zhou, Shuangnian Xu, Xi Li, Yunding Zou, Jieping Chen* Department of Hematology, Southwest Hospital, Third Military Medical University, Chongqing, China *
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Abstract OPEN ACCESS Citation: Gong Q, Zhou L, Xu S, Li X, Zou Y, Chen J (2015) High Doses of Daunorubicin during Induction Therapy of Newly Diagnosed Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis of Prospective Clinical Trials. PLoS ONE 10(5): e0125612. doi:10.1371/journal.pone.0125612 Academic Editor: Ken Mills, Queen's University Belfast, UNITED KINGDOM Received: February 6, 2015 Accepted: March 24, 2015 Published: May 20, 2015 Copyright: © 2015 Gong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The right dose of daunorubicin (DNR) for the treatment of newly diagnosed acute myeloid leukemia (AML) is uncertain. Previous trials have shown conflicting results concerning the efficacy of high or low doses of daunorubicin to induction chemotherapy for newly diagnosed AML. A systematic review and meta-analysis was conducted to resolve this controversial issue. We compared the efficacy and safety of high doses of daunorubicin (HDDNR) and traditional low doses of daunorubicin (LD-DNR) or idarubicin (IDA) during induction therapy of newly diagnosed AML. Data of 3,824 patients from 1,796 articles in the literature were retrieved and six randomized controlled trials were analyzed. The primary outcomes were overall survival (OS), disease-free survival (DFS), and event-free survival (EFS). The secondary outcomes included complete remission (CR), relapse, and toxicity. The meta-analysis results suggest that comparing HD-DNR with LD-DNR, there were significant differences in CR (RR = 1.19, 95%CI[1.12,1.18], p5% blasts in bone marrow not attributable to any other cause (eg, bone marrow regeneration after consolidation therapy), or appearance of extramedullary leukemia. Overall survival was measured from the date of random assignment until death which was due to any cause or was censored at the last follow-up. Event-free survival referred to the interval from entry into the study to the date of treatment failure, relapse from complete remission, or death due to any cause. Disease-free survival for patients who achieved complete remission was calculated from the date of complete remission until the date of relapse or death of any cause or was censored at the last follow up. Risk of bias was assessed for each individual study by two independent reviewers according to Cochrane Handbook for Systematic Reviews of Interventions (version 5.1.0).
Statistical analysis To systematically evaluate the treatment, dichotomous variables were pooled by using risk ratio (RR) as an effective measurement under the fixed-effect model while survival data were pooled by using hazard ratio (HR) under the fixed-effect model, with 95% confidence intervals respectively. If HR was not reported directly, it would be extracted from relevant Kaplan-Meier curves or calculated by data transformation[16]. Heterogeneity pooled studies was calculated by using I2 of chi-square-based Q test and ranked as low (50%)[17]. Heterogeneity was considered statistically significant if P
