Laboratory and morphologic changes during hydroxyurea dose escalation to MTD. Increases in hemoglobin (Hb), mean corpuscular volume (MCV), and percentage fetal hemoglobin (HbF) occur simultaneously with decreases in white blood cell count (WBC), absolute neutrophil count (ANC), ARC, and lactate dehydrogenase (LDH). Morphologic changes to the erythrocytes include nonreticulocyte macrocytosis, increased numbers of target cells, fewer sickled forms, and relative “blunting” of the sickled cells that remain in circulation. (A-C) Changes from baseline through dose escalation to maximum tolerated dose (MTD) for a child with high HbF response (∼ 30% HbF at 30 mg/kg/d). (D-F) Changes for a child with low HbF response (∼ 15% HbF at 25 mg/kg/d). Despite the differences in HbF response, both patients have marked improvements in the peripheral blood smear morphology. For all panels, images were visualized using an Olympus BX40 microscope (Olympus America) with a 100×/1.25 numeric aperture oil-immersion objective (Resolve Microscope immersion oil, Thermo Scientific); photographs were taken with an Olympus DP20-SE digital camera, processed using Olympus DP2-BSW application software, and displayed using Microsoft Office PowerPoint 2003. Photographs courtesy of Nicole A. Mortier.