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High-Dose Cytarabine (HD araC) in the Treatment of Leukemias: a Review

  • Acute Leukemias (E Feldman, Section Editor)
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Abstract

Cytarabine (araC) has served as the backbone of acute myeloid leukemia (AML) treatment for nearly forty years. High-dose cytarabine (HD araC) therapy resulted from a theoretical model developed in the 1970s that attempted to maximize the anti-leukemia effect of cytarabine. Since that time, HD araC has been utilized mostly in consolidation therapy for AML and in patients with relapsed or resistant AML. The development of araC and HD araC preceded our current understanding of AML biology–that it is a heterogeneous disease, not a single clinical entity. Thus, the optimal dose, schedule, and clinical setting for the use of cytarabine in hematologic malignancies remain uncertain. Research is now better defining the optimal use of HD araC based on leukemia cell karyotype and molecular signature. Here we review the pharmacodynamics of araC, the landmark studies that established the role of HD araC in AML, and research defining the role of HD araC based on the unique biologic properties of the leukemia cell.

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  1. Department of Internal Medicine, David Geffen School of Medicine at UCLA, 757 Westwood Plaza, Suite 7501, Los Angeles, CA, 90095, USA

    Nicholas D. Reese

  2. Department of Internal Medicine, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, 42-121 CHS, Los Angeles, CA, 90095, USA

    Gary J. Schiller

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This paper reviews the pharmacodynamics of cytarabine, as well as many of the preclinical studies that led to the use of cytarabine in the treatment of acute leukemia. In this manuscript, we detail common clinical uses of cytarabine in induction and consolidation therapy for newly diagnosed AML and its use in the treatment of resistant/relapsed AML. We also discuss a less common use – the treatment of central nervous system leukemia. There is also a focus on reviewing how leukemia cell karotype and molecular changes impact response to dose-intensified treatment with cytarabine.

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Reese, N.D., Schiller, G.J. High-Dose Cytarabine (HD araC) in the Treatment of Leukemias: a Review. Curr Hematol Malig Rep 8, 141–148 (2013). https://doi.org/10.1007/s11899-013-0156-3

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