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Arsenic Trioxide in APL

Studies on the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia: a comparison with conventional dosage

Leukemia volume 15, pages 735–741 (2001)Cite this article

Abstract

Twenty cases of patients with relapsed acute promyelocytic leukemia (APL) were entered into this study for evaluating the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide (As2O3). As2O3 was given at a daily dose of 0.08 mg/kg intravenously for 28 days. Pharmacokinetic study was carried out in eight patients. 16/20 (80%) patients achieved CR. The occurrence of some toxic events including gastrointestinal disturbance, facial edema and cardiac toxicity seemed reduced in the low-dose group than those in the standard-dose group. Differentiation changes were observed in peripheral blood, as well as in bone marrow (BM). Pharmacokinetic study showed that the plasma concentration increased soon after administration of As2O3 with the peak values of 1.535–3.424 μmol/l. After infusion, the plasma concentration was around 0.1–0.5 μmol/l. The arsenic concentration of the plasma of BM aspirates 24 h after administration in five patients was close to the level needed for differentiation-inducing effect. The estimated 2-year OS and RFS were 61.55 ± 15.79% and 49.11 ± 15.09% respectively, with no difference as compared with those in patients treated with conventional dose (P = 0.2865 and 0.7146, respectively). In conclusion, we demonstrated that low-dose As2O3 had the same effect as the conventional dosage and the mechanism of low-dose arsenic seemed to primarily induce differentiation of APL cells.

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Acknowledgements

This work was supported in part by the National Natural Science Foundation of China and the Clyde Wu Foundation of Shanghai Institute of Hematology. The authors thank all members of Shanghai Institute of Hematology for providing patient samples and clinical data.

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  1. Shanghai Institute of Hematology, Rui Jin Hospital, Shanghai Second Medical University, 197 Rui Jin Road II, Shanghai, 200025, PR China

    Y Shen, Z-X Shen, H Yan, J Chen, X-Y Zeng, J-M Li, X-S Li, W Wu, S-M Xiong, W-L Zhao, W Tang, F Wu, Y-F Liu, C Niu, Z-Y Wang, S-J Chen & Z Chen

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Shen, Y., Shen, ZX., Yan, H. et al. Studies on the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia: a comparison with conventional dosage. Leukemia 15, 735–741 (2001). https://doi.org/10.1038/sj.leu.2402106

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