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Risk factors for early death after high-dose cytosine arabinoside (HiDAC)-based chemotherapy for adult AML

Leukemia volume 26, pages 362–365 (2012)Cite this article

The primary goal of initial therapy in acute myeloid leukemia (AML) is the effective and prompt achievement of complete remission without excessive morbidity and mortality, paving the way for post-remission strategies, including allogeneic stem cell transplantation. High-dose cytarabine (HiDAC) is an established component of most treatment regimens for adult AML and is incorporated into either the induction or consolidation phase of intensive chemotherapy. HiDAC-based consolidation therapy significantly improves the survival of adult patients with AML up to the age of 60 years. Attempts to further improve treatment outcomes in AML have led to studies investigating the role of HiDAC during AML induction. Randomized comparisons have consistently shown that HiDAC-based induction chemotherapy results in a higher complete remission rate after the first cycle of therapy, compared with standard dose ara-C induction. Complete remission rates of 77% after a single induction cycle can be achieved using HiDAC in combination with idarubicin and etoposide, compared with 41–66% with standard dose ara-C.1, 2, 3 Although HiDAC-based induction achieves good early disease control, the benefits are offset by excessive induction-related toxicity and an increased risk of early death compared with standard dose ara-C. The definition of induction-related death varies widely between reports, making cross-study comparisons difficult. In patients under the age of 60 years, standard dose ara-C-based induction is associated with an early mortality rate of between 6–13%.4, 5, 6 Early mortality after HiDAC induction ranges between 7–18%.3, 4, 6, 7, 8

Identification of baseline risk factors predictive of early treatment-related mortality in adult AML after HiDAC-based induction therapy in a cooperative group setting has not been reported. A risk-stratified approach limiting HiDAC induction regimens to AML patients with a lower risk of early treatment-related mortality may be helpful in limiting factors that may contribute to iatrogenic death. This report identifies clinical variables associated with higher treatment-related mortality after HiDAC-based intensive chemotherapy in the Australasian Leukemia and Lymphoma Group (ALLG) AML M7 study.

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Acknowledgements

We thank the Australasian Leukemia and Lymphoma Group and the Centre for Biostatistics and Clinical Trials for compiling clinical data and ALLG physicians for recruiting patients to the ALLG M7 study.

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  1. A van der Jagt and J Muirhead: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Clinical Hematology, The Alfred Hospital, Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia

    A van der Jagt, J Muirhead & A Wei

  2. Department of Hematology, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia

    J F Seymour

  3. Westmead Hospital, Westmead, New South Wales, Australia

    K F Bradstock

  4. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia

    E Paul

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  1. A van der Jagt
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Correspondence to A Wei.

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van der Jagt, A., Muirhead, J., Seymour, J. et al. Risk factors for early death after high-dose cytosine arabinoside (HiDAC)-based chemotherapy for adult AML. Leukemia 26, 362–365 (2012). https://doi.org/10.1038/leu.2011.201

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