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.

Rapid Reduction in Breast Cancer Mortality With Inorganic Arsenic in Drinking Water

“…We are not aware of any data on breast tissue arsenic concentrations, but studies after acute poisoning find arsenic to be distributed in most organs throughout the body ( Benramdane et al, 1999 ). It is also likely that some methylated inorganic arsenic, in particular MMA and DMA in trivalent form, could contribute to breast cancer apoptosis in addition to the activity of inorganic arsenic itself ( Zhang et al, 2013 ).…”

Arsenic toxicity manifesting as profuse watery diarrhea during induction therapy for acute promyelocytic leukemia

“…Other acute toxicities can include anemia, peripheral neuropathy, hyperpigmentation, and fatal arrhythmias 5‐7 . Chronic exposures have resulted in cancers of the skin, bladder, kidney, and lung 7 …”

“…5 Environmental exposure to arsenic compounds can lead to gastrointestinal toxicities including nausea, vomiting, hemorrhage, and large-volume watery diarrhea. [5][6][7] Other acute toxicities can include anemia, peripheral neuropathy, hyperpigmentation, and fatal arrhythmias. [5][6][7] Chronic exposures have resulted in cancers of the skin, bladder, kidney, and lung.…”

“…3 Since there are other forms of arsenic and several metabolites of varying toxicities, including relatively nontoxic forms from fish and other foods (arsenobetaine, arseno sugars), speciation of urine arsenic samples is recommended where possible rather than measurement of total urine arsenic alone. Variations in susceptibility to ATO toxicity and the rate of ATO metabolism have been observed between populations, which may be due to polymorphisms of multiple methylation genes 7 and differences in gut microbiome. 8 Within the context of APL therapy, underlying comorbidities may also potentially contribute to an increased risk of ATO toxicity.…”

“…[5][6][7] Other acute toxicities can include anemia, peripheral neuropathy, hyperpigmentation, and fatal arrhythmias. [5][6][7] Chronic exposures have resulted in cancers of the skin, bladder, kidney, and lung. 7 While the toxicity of arsenic has long been established, the beneficial role of ATO as a highly effective differentiating therapy of APL was only more recently identified.…”