Hyperleukocytic Leukemias and Leukostasis: A Review of Pathophysiology, Clinical Presentation and Management

Abstract

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.

FLT-3 ITD Positive Acute Basophilic Leukemia with Rare Complex Karyotype Presenting with Acute Respiratory Failure: Case Report

“…Ground glass opacities sparing the lung bases and the subpleural space are evocative of non-cardiogenic pulmonary edema. Pulmonary leukostasis requires endothelial cell activation and expression of various adhesion molecules by the leukemic blasts, including CD56, irrespective of the absolute leukocyte count [21,22]. In this case, CD56 expression on basophilic blasts might have specifically facilitated the development of leukostasis.…”

“…Differential diagnosis includes other myeloid neoplasms associated with basophilia, namely AML with t(6;9)(p23;q14), acute promyelocytic leukemia with basophilic differentiation, blastic transformation of chronic myelogenous leukemia, primary myelofibrosis, or rare acute lymphoblastic leukemia cases with prominent cytoplasmic granules [1,4]. Noteworthy, even though multiple chromosomal abnormalities have been reported involving chromosomes 1, 2,6,7,8,11,12,16,17,19,21 and X, no recurrent cytogenetic or molecular anomalies have been described in acute basophilic leukemia patients [3,[5][6][7][8][9][10][11][12][13]. Acute basophilic leukemia management remains poorly defined, relying on cytarabine and anthracycline-based induction regimens, palliative cytoreductive treatment, targeted therapies (tyrosine kinase inhibitors) or allogeneic stem cell transplant in selected cases [7,14].…”

Clinical and biologic features and treatment outcome of children with newly diagnosed acute myeloid leukemia and hyperleukocytosis

“…[1][2][3][4][5][6][7] Leukapheresis often is recommended for hyperleukocytosis in patients with AML because of its quick cytoreductive effect. 8 However, a recent study of an adult cohort failed to demonstrate that leukapheresis is associated with an improved early mortality rate.…”

Congenital Leukemia Presenting as Fever in a Neonate

“…Hyperleukocytosis is seen in 10% to 30% of patients with newly diagnosed ALL (15). High leukemic cell burden increases blood viscosity and causes white blood cell plugging, referred to as leukostasis.…”