Wen Cui1,2, Jin Wang1, Rui-Min Nie1, Ling-Ling Zhao3, Meng-Qing Gao1, Hong-Ming Zhu1, Li Chen1, Jiong Hu1, Jun-Min Li1, Zhi-Xiang Shen1, Zhen-Yi Wang1, Sai-Juan Chen1, Zhu Chen1, Kan-Kan Wang1, Xiao-Dong Xi1,4, Jian-Qing Mi1. 1. Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics and Department of Hematology, Collaborative Innovation Center of Systems Biomedicine, Pôle Sino-Français des Sciences du Vivant et Genomique, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. 2. Department of Clinical Laboratory, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China. 3. Department of Clinical Laboratory, Shanghai Xuhui Central Hospital, Shanghai, China. 4. Collaborative Innovation Center of Hematology, Shanghai, China.
Abstract
OBJECTIVES: The arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA) therapy has demonstrated a tremendous success in the first-line treatment of acute promyelocytic leukemia (APL). Actually, early death (ED) is currently thought as a major challenge in APL. ATO has been reported to inhibit platelet function in vitro, and whether it increases the ED rate by exacerbating the hemorrhagic symptoms remains to be investigated. METHODS: Effects of ATO on platelet aggregation and adhesion were evaluated in vitro and in thirty-two complete remission (CR) and four newly diagnosed APL patients. Furthermore, concentrations of plasma total arsenic were monitored in APL patients via ICP-MS. RESULTS: The inhibition of platelet function, either aggregation or adhesion, did occur in vitro when the concentration of ATO reached 2 μmol/L. However, in CR APL patients receiving ATO with normal platelet count, the platelets responded normally when being activated and so did those in the newly diagnosed patients with thrombocytopenia. Our data further showed that the conventional dosage of ATO reached a plasma concentration substantially below the required concentration to inhibit platelets. CONCLUSIONS: In the first-line treatment of APL, the use of ATO is safe and effective and does not compromise the hemostatic potential that may eventually increase ED rate.
OBJECTIVES: The arsenic trioxide (ATO) plus all-transretinoic acid (ATRA) therapy has demonstrated a tremendous success in the first-line treatment of acute promyelocytic leukemia (APL). Actually, early death (ED) is currently thought as a major challenge in APL. ATO has been reported to inhibit platelet function in vitro, and whether it increases the ED rate by exacerbating the hemorrhagic symptoms remains to be investigated. METHODS: Effects of ATO on platelet aggregation and adhesion were evaluated in vitro and in thirty-two complete remission (CR) and four newly diagnosed APLpatients. Furthermore, concentrations of plasma total arsenic were monitored in APLpatients via ICP-MS. RESULTS: The inhibition of platelet function, either aggregation or adhesion, did occur in vitro when the concentration of ATO reached 2 μmol/L. However, in CR APLpatients receiving ATO with normal platelet count, the platelets responded normally when being activated and so did those in the newly diagnosed patients with thrombocytopenia. Our data further showed that the conventional dosage of ATO reached a plasma concentration substantially below the required concentration to inhibit platelets. CONCLUSIONS: In the first-line treatment of APL, the use of ATO is safe and effective and does not compromise the hemostatic potential that may eventually increase ED rate.
Authors: Thomas T Huynh; Mohammad Sultan; Dejan Vidovic; Cheryl A Dean; Brianne M Cruickshank; Kristen Lee; Chao-Yu Loung; Ryan W Holloway; David W Hoskin; David M Waisman; Ian C G Weaver; Paola Marcato Journal: Sci Rep Date: 2019-07-01 Impact factor: 4.379