Determination of arsenic metabolites in patients with newly diagnosed acute promyelocytic leukemia treated with arsenic trioxide

Abstract

The efficacy of arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL) is widely accepted. It is necessary to determine the concentration of arsenic due to its toxicity. The profiles of arsenic speciation in patients with relapsed or refractory APL have been demonstrated in few reports. Arsenic metabolite concentrations in the plasma of patients with newly diagnosed APL during the first course of arsenic remission induction therapy were determined, and the complicated change pattern of these metabolite concentrations in this phase is described for the first time in this study. We demonstrated that the concentration of trivalent inorganic arsenic (As^III), which is regarded as the most effective and toxic, was much lower than those of other metabolites. Concentrations of the same arsenic metabolites were obviously distinct among various individuals. We infer that determination of the metabolites separately is necessary, and cannot be replaced by total arsenic determination. In addition, the amount of methylated metabolites of arsenic increased during the first course of ATO therapy, and these metabolites might therefore play an increasingly important role. Further research should be carried out to study the relationship between arsenic metabolite concentrations and efficacy, as well as side effects in patients with APL treated with ATO.

Keywords::

• Acute promyelocytic leukemia
• arsenic trioxide
• trivalent inorganic arsenic
• pentavalent inorganic arsenic
• monomethylarsonic acid
• dimethylarsinic acid

Acknowledgements

We thank Drs. Fenglin Cao and Xiuhua Liu (Central Laboratory of Hematology and Oncology, the First Affiliated Hospital, Harbin Medical University) for providing some indispensable instruments, and Drs. Jinmei Li, Shuye Wang, Yanhua Su, Yinghua Li, Yanhong Zhao and Limin Li (Department of Hematology, the First Affiliated Hospital, Harbin Medical University) for the collection of samples.

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This work was supported partially by grants from the Technology and Innovation Team of the Colleges and University of Heilongjiang Province (2010td07), the Special Fund for Scientific Researchers in Harbin (2011RFQYS082), the Special Fund for Doctor Stations, Ministry of Education, China (20122307130003), and the Fund for Doctors of the First Affiliated Hospital, Harbin Medical University (2012B07).