Figure 2.

(A) White blood cell counts were measured every time the patient was seen at our institution. The beginning and end of cycles of darinaparsin treatment are demarcated with vertical lines. Note that the x-axis is not to scale. (B) Micrograph of peripheral blood smear stained with Wright’s Giemsa stain while the patient was on darinaparsin treatment. Nuclear blebbing suggests cells are dying by apoptosis. (C) While the patient was in hospital, her temperature was monitored daily (measured in degrees Celsius). The temperature curve has been overlaid graphs showing expression of circulating cytokines in plasma, measured by a multiplex immunoassay kit. Only three out of the 11 cytokines measured by the kit were detected at levels above the assay’s limit of detection. IL-8, interleukin 8; IL-10, interleukin 10; TNF-α, tumor necrosis factor-alpha. Samples taken prior to starting treatment with darinaparsin are labeled “Pre” while time points during and after darinaparsin treatment are labeled with cycle number (C1, cycle 1; h, hours; d, days) and time on or off darinaparsin treatment. The patient was allowed to go home 3 days after completing her first course of darinaparsin. Elemental arsenic levels were measured in patient plasma (D) and peripheral blood mononuclear cells (PBMCs) (E) by inductively coupled plasma mass spectrometry. The highest plasma level of arsenic measured with this dosing schedule was approximately 90 parts per billion (ppb). Given arsenic’s molar mass of 75 g/mol, this is equal to a plasma concentration of 1.2 μM, which corresponds well with the doses used for ex vivo experiments in Figures 1C,D.