EFFECTS OF ARSENIC TRIOXIDE ADMINISTRATION STYLES ON LEUKOCYTOSIS

Objective To study the effects of constantly slow intravenous arsenic trioxide （As_ 2 O_ 3 ） infusion regimen on decreasing leukocytosis in vivo and in vitro. Methods Three kinds of leukemia cells, NB4, K562, and acute promyelocytic leukemia （APL） cells, were cultured in the media with constant concentration and varying concentrations of As_ 2 O_ 3 respectively for 24 hours. Seventy-five patients were enrolled in two groups randomly. In trial group, 37 patients received continuously slow intravenous As_ 2 O_ 3 infusion regimen for 24 hours with an infusion rate of 8 drips per minute and total infusion duration of about 18-21 hours daily. In control group, 38 patients received routine regimen with an infusion rate of 45-55 drips per minute and total infusion duration of about 2-3 hours daily for 24 hours. The daily As_ 2 O_ 3 dosage was 0.16 mg/kg. The intracellular arsenic concentration was measured by atomic fluorescence assay. The apoptosis rate of cells, CD33~ - CD11b~ + cells, and CD33~ + CD11b~ - cells were monitored by flow cytometry. Results The apoptosis rates of NB4, K562, and APL leukemia cells in the media with constant As_ 2 O_ 3 concentration were 56.6%±2.4%, 27.6%±3.1%, and 52.2%±2.8%, respectively, which were significantly higher than those with changing As_ 2 O_ 3 concentration （23.2%±2.1%, 11.0%±2.5%, and 21.0%±2.5%, respectively, P<0.01）. The apoptosis rates of APL, M2 type acute myeloid leukemia （AML-M2）, and chronic myeloid leukemia （CML） patients in the trial group （28.5%±1.9%, 9.5%±0.6%, and 12.5%±1.8%） were also significantly higher than those in control group （8.5%±2.2%, 2.9%±0.8%, and 4.5%±1.2%; P<0.05）. The ratios of CD33~ + CD11b~ - and CD33~ - CD11b~ + cells in control group were significantly higher than those in trial group. Conclusion The continuously slow intravenous As_ 2 O_ 3 infusion regimen can obtain high efficiency of apoptosis and low differentiation proportion, relieve leukocytosis, and gain maximal therapeutic benefit.