Meihua Guo1, Jin Zhou2, Shengjin Fan3, Limin Li2, Hongzhu Chen1, Liwang Lin1, Qilei Zhao1, Xinyu Wang1, Wensheng Liu1, Zhiqiang Wu1, Xin Hai1. 1. Department of Pharmacy, First Affiliated Hospital of Harbin Medical University, Harbin, China. 2. Department of Hematology, Southern University of Science and Technology Hospital, Shenzhen, China. 3. Department of Hematology, First Affiliated Hospital of Harbin Medical University, Harbin, China.
Abstract
Background: Arsenic trioxide (ATO) is successfully applied to treat acute promyelocytic leukemia (APL). Arsenic species levels in blood are critical to reveal metabolic mechanism and relationship between arsenic species and clinical response. Characteristics and influence factors of arsenic species in APL patients have not been studied. Methods: 305 plasma samples from APL patients treated with ATO were analyzed using HPLC-HG-AFS. Trough concentration (Ctrough), distribution, methylation levels of arsenic species were evaluated. The influence factors on arsenic species levels of plasma and association between arsenic concentrations and clinical efficacy were explored. Results: Ctrough of arsenic in effective treatment groups provide basis for defining the target range of arsenic plasma concentrations in APL patients treated with ATO. Distribution trends: DMAV > AsIII, MMAV> AsV (p < 0.0001) for continuous slow-rate (CS) infusion and DMAV > MMAV > AsIII > AsV (p < 0.0001) for conventional infusion. Infusion methods and combined medication may affect arsenic metabolism. There was a weak correlation between ATO dose and plasma Ctrough of arsenic species. Ctrough of plasma arsenic species had predictive value for treatment efficacy. Conclusion: Arsenic concentration monitoring in APL patients treated with ATO is required. These findings are critical to optimize treatment outcomes of ATO therapy.
Background: Arsenic trioxide (ATO) is successfully applied to treat acute promyelocytic leukemia (APL). Arsenic species levels in blood are critical to reveal metabolic mechanism and relationship between arsenic species and clinical response. Characteristics and influence factors of arsenic species in APLpatients have not been studied. Methods: 305 plasma samples from APLpatients treated with ATO were analyzed using HPLC-HG-AFS. Trough concentration (Ctrough), distribution, methylation levels of arsenic species were evaluated. The influence factors on arsenic species levels of plasma and association between arsenic concentrations and clinical efficacy were explored. Results: Ctrough of arsenic in effective treatment groups provide basis for defining the target range of arsenic plasma concentrations in APLpatients treated with ATO. Distribution trends: DMAV > AsIII, MMAV> AsV (p < 0.0001) for continuous slow-rate (CS) infusion and DMAV > MMAV > AsIII > AsV (p < 0.0001) for conventional infusion. Infusion methods and combined medication may affect arsenic metabolism. There was a weak correlation between ATO dose and plasma Ctrough of arsenic species. Ctrough of plasma arsenic species had predictive value for treatment efficacy. Conclusion:Arsenic concentration monitoring in APLpatients treated with ATO is required. These findings are critical to optimize treatment outcomes of ATO therapy.