Leukostasis, a complication of acute leukemia, occurs when leukemia cells aggregate in and obstruct the microvasculature, leading to profound damage of vital organs like the brain and lungs. The underlying mechanisms are poorly understood but are likely related to the abnormal mechanical properties of leukemia cells. Using atomic force microscopy and microfluidic devices to quantify cell deformation, I found that leukemia cells taken from patients with leukostasis were significantly stiffer than leukemia cells taken from asymptomatic patients. These results suggest that increased leukemia cell stiffness may be an independent leukostasis risk factor and could be useful for predicting leukostasis. In addition, I found that chemotherapy increases leukemia cell stiffness by up to 100x and therefore, may actually increase leukostasis risk. However, the phosphodiesterase inhibitor pentoxifylline substantially decreased leukemia cell stiffness and adhesiveness, and this drug may be a potential treatment for leukostasis. Overall, these studies show that cell mechanics are relevant in disease. In addition, tools that measure cell mechanics can be useful diagnostic/drug discovery platforms.