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 leukostasis but the biological mechanisms underlying its development and progression remain unclear. Although traditionally related to "over-crowding" of leukemic blasts in the capillaries of the microcirculation, leukostasis is likely to result from direct endothelial cell damage. This damage is probably mediated by soluble cytokines released during the interaction between leukemic cells and vascular endothelium and by the subsequent migration of leukemic blasts in the perivascular space. Leukemic cell's ability to respond to chemotactic cytokines and their expression of specific adhesion molecules are probably more important in determining whether leukostasis will develop than the number of circulating blasts. This could explain why leukostasis does not develop in all patients with AHL. The identification of the adhesion molecules, cytokines and receptors mediating endothelial cell damage in AHL should become a priority if therapeutic improvements are desired. Leukapheresis is widely used but it is unclear whether it provides additional benefit to a simpler and less invasive intervention with allopurinol, hydroxyurea and intravenous fluids. Cranial irradiation is not generally recommended. Induction chemotherapy should be started without delay. It is hoped that specific pharmacological inhibitors of the interaction between leukemic cells and vascular endothelium will result in an improved outcome for this very high-risk population.