Original Research Article Conventional and high-dose daunorubicin and idarubicin in acute myeloid leukaemia remission induction treatment: a mixed treatment comparison meta-analysis of 7258 patients † Leo Sekine 1,5 * , Vinícius Daudt Morais 1 , Karine Margarites Lima 1,5 , Tor Gunnar Hugo Onsten 2 , Patrícia Klarmann Ziegelmann 1,3,4 and Rodrigo Antonini Ribeiro 1,4,5 1 Post-Graduate Program in Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil 2 Internal Medicine Department, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil 3 Statistics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil 4 National Institute of Science and Technology for Health Technology Assessment, CNPq, Porto Alegre, Brazil 5 Institute for Research and Education, Hospital Moinhos de Vento, Porto Alegre, Brazil *Correspondence to: Leo Sekine, Hospital de Clínicas de Porto Alegre, Rua São Manoel, 543/2° andar, Porto Alegre, RS, Brazil—CEP 90620-110. E-mail: lsekine@hcpa.ufrgs.br † No financial support was received in any form during this research. Received 14 August 2014 Accepted 29 August 2014 Abstract Previous meta-analyses suggested that acute myeloid leukaemia induction regimens con- taining idarubicin (IDA) or high-dose daunorubicin (HDD) induce higher rates of complete remission (CR) than conventional-dose daunorubicin (CDD), with a possible benefit in overall survival. However, robust comparisons between these regimens are still lacking. We conducted a mixed treatment comparison meta-analysis regarding these three regi- mens. Mixed treatment comparison is a statistical method of data summarization that aggregates data from both direct and indirect effect estimates. Literature search strategy included MEDLINE, EMBASE, Cochrane, Scielo and LILACS, from inception until August 2013 and resulted in the inclusion of 17 trials enrolling 7258 adult patients. HDD [relative risk (RR) 1.13; 95% credible interval (CrI) 1.02–1.26] and IDA (RR 1.13; 95% CrI 1.05–1.23) showed higher CR rates than CDD. IDA also led to lower long-term overall mortality rates when compared with CDD (RR 0.93, 95% CrI 0.86–0.99), whereas HDD and CDD were no different (RR 0.94, 95% CrI 0.85–1.02). HDD and IDA comparison did not reach statistically significant differences in CR (RR 1.00; 95% CrI 0.89–1.11) and in long-term mortality (RR 1.01, 95% CrI 0.91–1.11). IDA and HDD are consistently superior to CDD in inducing CR, and IDA was associated with lower long-term mortality. On the basis of these findings, we recommend incorporation of IDA and HDD instead of the traditional CDD as standard treatments for acute myeloid leukaemia induction. The lack of HDD benefit on mortality, when compared with CDD in this study, should be cautiously addressed, because it may have been susceptible to underestimation because of statistical power limitations. Copyright © 2014 John Wiley & Sons, Ltd. Keywords: acute myeloid leukaemia; anthracyclines; daunorubicin; idarubicin; induction chemotherapy; remission induction Introduction Progress in the management of acute myeloid leukaemia (AML) was far from satisfactory throughout the last century. Indeed, a steady yet slow increase in survival was observed over the years, but it was due predominantly to the improve- ment of supportive therapies [1]. Chemotherapy with a combination of an anthracycline and cytarabine remains a thoroughly accepted induction treatment for almost 40 years [2–4]. Daunorubicin (DNR) at a conventional-dose (CDD), that is, in a schedule of up to 180mg/m 2 per cycle of chemotherapy, together with cytarabine, in a dosage of 100–200 mg/m 2 for 5–7 days, is still considered the standard choice, amongst anthracycline derivatives, for de novo adult AML in many hematology–oncology reference centres [5–7]. Several randomized clinical trials (RCTs) compared dif- ferent anthracycline derivatives and schedules in induction therapy of AML. Previous attempts to compile these stud- ies resulted in few systematic reviews [1,8–10]. In 1998, the AML Collaborative Group observed that idarubicin (IDA), a direct derivative from DNR, could offer a higher rate of complete remission (CR) and overall survival Hematological Oncology Hematol Oncol (2014) Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/hon.2173 Copyright © 2014 John Wiley & Sons, Ltd.