DESCRIPTION

Hyperleukocytosis is a total white blood cell (WBC) count of ≥100,000/μL, typically caused by leukemic cell proliferation. Complications including leukostasis, tumor lysis syndrome (TLS), and disseminated intravascular coagulation from a high blood count put patients at risk of poor outcomes.

RISK FACTORS

• Presentation with hyperleukocytosis depends on the type of leukemia.
• Percentage with hyperleukocytosis
  • Chronic myeloid leukemia (CML) especially in blast crisis <100%
  • Acute myeloid leukemia (AML) especially in infants 5–20%
  • Acute lymphoblastic leukemia (ALL) especially with mediastinal mass 8–13%
• Factors associated with more severe clinical course:
  • Coagulopathy
  • Metabolic derangements secondary to TLS
• Mortality associated more with clinical symptoms from leukostasis (central nervous system [CNS] or respiratory) than with WBC
• Children with trisomy 21 (Down syndrome) have an increased risk of developing transient leukemoid reactions and have an increased risk of developing acute leukemia, more commonly ALL.

PATHOPHYSIOLOGY

• The primary mechanism for development of hyperleukocytosis is due to rapid blast proliferation leading to a high leukemic tumor burden with disruption of normal hematopoietic cell adhesion leading to reduced affinity to the bone marrow. Symptomatology results from leukostasis due to increased viscosity and impaired blood flow. Contributory factors other than the number of leukemic cells include their shape and size, which increases viscosity, as well as endothelial cell damage, which further impedes microcirculation.
• WBCs lack the concave shape that enables reversible deformability that is characteristic of red blood cells (RBCs), allowing passage through the microvasculature. As compared to normal WBCs, blasts are much larger with less deformability.
• Myeloblasts are twice the size of lymphoblasts, and lymphoblasts are 25% larger than mature neutrophil granulocytes. Monoblasts are larger than myeloblasts. Aggregates of these large, undeformable cells cannot pass through capillaries.
• In addition to increased cell-to-cell adhesions, leukemic blasts have increased adhesion to the damaged endothelium, which promotes additional cell aggregates through endothelial toxin and cytokine release.
• Leukemic cells have a hypersensitive response to cytokines, which may account for clinical leukostasis at lower peripheral blast counts.
• Leukostasis impairs blood flow and exacerbates hypoxemia; as expected, leukemic blasts have increased oxygen consumption due to a high rate of cell division.