Anthracyclines during induction therapy in acute myeloid leukaemia: a systematic review and meta-analysis

Authors

  • Oliver Teuffel,

    1. Division of Haematology/Oncology, University Children's Hospital Berne, Berne, Switzerland
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  • Kurt Leibundgut,

    1. Division of Haematology/Oncology, University Children's Hospital Berne, Berne, Switzerland
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  • Thomas Lehrnbecher,

    1. Paediatric Haematology and Oncology, Children's University Hospital, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
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  • Todd A. Alonzo,

    1. University of Southern California, Los Angeles, CA, USA
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  • Joseph Beyene,

    1. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada
    2. Department of Clinical Epidemiology & Biostatistics, McMaster University, Hamilton, ON, Canada
    3. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
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  • Lillian Sung

    Corresponding author
    1. Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada
    2. Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, ON, Canada
    3. Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, ON, Canada
    • Division of Haematology/Oncology, University Children's Hospital Berne, Berne, Switzerland
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Correspondence: Dr Lillian Sung, Division of Haematology/Oncology, The Hospital for Sick Children 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada.

E-mail: lillian.sung@sickkids.ca

Summary

This systematic review and meta-analysis compared the efficacy of different anthracyclines and anthracycline dosing schedules for induction therapy in acute myeloid leukaemia in children and adults younger than 60 years of age. Twenty-nine randomized controlled trials were eligible for inclusion in the review. Idarubicin (IDA), in comparison to daunorubicin (DNR), reduced remission failure rates (risk ratio (RR) 0·81; 95% confidence interval (CI), 0·66–0·99; = 0·04), but did not alter rates of early death or overall mortality. Superiority of IDA for remission induction was limited to studies with a DNR/IDA dose ratio <5 (ratio <5: RR 0·65; 95% CI, 0·51–0·81; < 0·001; ratio ≥5: RR 1·03; 95% CI, 0·91–1·16; = 0·63). Higher-dose DNR, compared to lower-dose DNR, was associated with reduced rates for remission failure (RR 0·75; 95% CI, 0·60–0·94; = 0·003) and overall mortality (RR 0·83; 95% CI, 0·75–0·93; < 0·001), but not for early death. Comparisons of several other anthracycline derivates did not reveal significant differences in outcomes. Survival estimates in adults suggest that both high-dose DNR (90 mg/m2 daily × 3 or 50 mg/m2 daily × 5) and IDA (12 mg/m2 daily × 3) can achieve 5-year survival rates of between 40 and 50 percent.

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