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Adding ascorbic acid to arsenic trioxide produces limited benefit in patients with acute myeloid leukemia excluding acute promyelocytic leukemia

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Abstract

Arsenic trioxide (ATO) is highly effective in acute promyelocytic leukemia (APL), but despite its multiple mechanism of action, it has no activity in acute myeloid leukemia (AML) that excludes APL (non-APL AML). Ascorbic acid (AA) and ATO induces apoptosis in AML cell lines by depleting intracellular glutathione and generation of reactive oxygen species. In this study, we evaluated the effect of ATO plus AA in patients with non-APL AML. The study enrolled patient aged 18 or older with relapsed or refractory AML (non-APL) after conventional chemotherapy or previously untreated patients 55 years or older who were unfit for standard induction chemotherapy for AML. Intravenous ATO (0.25 mg/kg/day over 1–4 h) was given with intravenous AA (1 g/day over 30 min after ATO) for 5 days a week for 5 weeks (25 doses). Eleven AML patients were enrolled, including six previously untreated elderly patients aged 66–84 years in whom five had antecedent hematological disorder (ADH). Among 10 evaluable patients, one achieved a CR one a CRi and 4 patients had disappearance of blasts from peripheral blood and bone marrow. Five of the six responders were seen in previously untreated elderly patients. ATO related toxicity was mild. The combination of ATO and AA has limited clinical meaningful antileukemia activity in patients with non-APL AML.

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Acknowledgments

The study was supported by a National Cancer Institute grant R21 CA0998650-02 and by a research grants from Cell Therapeutics Inc. and Cephalon Inc.

Statement to the effect of human studies

The study was approved by the institutional review board of University of Southern California, and a written informed consent was obtained from all patients before study entry.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Division of Hematology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Ibrahin Aldoss, Lisa Mark, Janice Vrona, Laleh Ramezani, Ilene Weitz & Ann M. Mohrbacher

  2. Leukemia Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College, 1275 York Ave, New York, NY, 10065, USA

    Dan Douer

Authors
  1. Ibrahin Aldoss
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  2. Lisa Mark
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  3. Janice Vrona
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  4. Laleh Ramezani
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  5. Ilene Weitz
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  6. Ann M. Mohrbacher
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  7. Dan Douer
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Correspondence to Dan Douer.

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Aldoss, I., Mark, L., Vrona, J. et al. Adding ascorbic acid to arsenic trioxide produces limited benefit in patients with acute myeloid leukemia excluding acute promyelocytic leukemia. Ann Hematol 93, 1839–1843 (2014). https://doi.org/10.1007/s00277-014-2124-y

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  • DOI: https://doi.org/10.1007/s00277-014-2124-y

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