Hyperleukocytic leukemias and leukostasis: A review of pathophysiology, clinical presentation and management

Acute hyperleukocytic leukemias (AHL) are associated with a very high early mortality rate mostly due to respiratory failure or intracranial bleeding. The pathophysiological process leading to these complications is called le ukostasis but the biological mechanisms underlying its development and prog ression remain unclear. Although traditionally related to "overcrowding" of leukemic blasts in the capillaries of the microcirculation, leukostasis is likely to result from direct endothelial cell damage. This damage is proba bly mediated by soluble cytokines released during the interaction between l eukemic cells and vascular endothelium and by the subsequent migration of l eukemic blasts in the perivascular space. Leukemic cell's ability to respon d to chemotactic cytokines and their expression of specific adhesion molecu les are probably more important in determining whether leukostasis will dev elop than the number of circulating blasts. This could explain why leukosta sis does not develop in all patients with AHL. The identification of the ad hesion molecules, cytokines and receptors mediating endothelial cell damage in AHL should become a priority if therapeutic improvements are desired. L eukapheresis is widely used but it is unclear whether it provides additiona l benefit to a simpler and less invasive intervention with allopurinol, hyd roxyurea and intravenous fluids. Cranial irradiation is not generally recom mended. Induction chemotherapy should be started without delay. It is hoped that specific pharmacological inhibitors of the interaction between leukem ic cells and vascular endothelum will result in an improved outcome for thi s very high-risk population.