Sorafenib treatment response. (A) Patient 2: A fast response to sorafenib was associated with a dephosphorylation of the antiapoptotic FLT3-ITD target STAT-5, measured intracellularly in the blastic population by fluorescence-activated cell sorter (middle panel histogram): the left shift of the green curve documents a decrease in intracellular STAT-5 phosphorylation 7 days after commencing sorafenib compared with baseline (day 0, red line). Sorafenib was withdrawn on day 204 of sorafenib and hydroxyurea commenced because of a newly diagnosed cerebral mass. AML was resistant to hydroxyurea (peripheral white blood cell count increase to 75.6 × 109/L), but reexposure to sorafenib again led to an instant response (white blood cell count decline to 1.3 × 109/L). (B) Patient 5: Bone marrow light microscopy to evaluate bone marrow response (patient 5) before allo-SCT. Giemsa staining shows blast infiltration before (left panels) and extensive blast clearance 14 days after commencing sorafenib (right panels). Low and high magnification of bone marrow smear (top and bottom panels, respectively). Images were viewed with an Olympus BH-2 microscope using Giemsa stain; left panel, 10×/0.3 numeric aperture (NA); right panel, 60×/1.4 NA oil objective. Images were taken with a Sony Exwave HAD camera using DHS Bilddatenbank software (Dietermann & Heuser Solution GmbH, Greifenstein-Beilstein, Germany).
