What is hyperleukocytosis?

Hyperleukocytosis: Definition and Management

Hyperleukocytosis is defined as an extremely elevated white blood cell count greater than 100,000/μL in patients with acute or chronic leukemias, representing a medical emergency that requires immediate intervention to prevent potentially fatal complications. 1, 2, 3

Definition and Pathophysiology

• Hyperleukocytosis is arbitrarily defined as a white blood cell count exceeding 100,000/μL, most commonly seen in patients with newly diagnosed or relapsed acute leukemias 3, 4
• It occurs more frequently in acute myeloid leukemia (AML) than in chronic leukemias, with risk factors including younger age, specific AML subtypes (particularly microgranular variant of acute promyelocytic leukemia), and certain cytogenetic abnormalities 5
• Hyperleukocytosis can lead to leukostasis, which refers to symptomatic hyperleukocytosis characterized by reduced blood flow due to hyperviscosity and microvascular obstruction 4, 6

Clinical Manifestations

• Hyperleukocytosis can affect any organ system, but symptoms typically arise from involvement of the cerebral, pulmonary, and renal microvasculature 5
• The main sites injured from leukostasis are the central nervous system and lungs 3
• Complications include:
  • Leukostasis (symptomatic hyperleukocytosis)
  • Tumor lysis syndrome
  • Disseminated intravascular coagulopathy 3, 6

Management Approach

Immediate Interventions

• Hyperleukocytosis should be treated as a medical emergency requiring prompt recognition and initiation of therapy 2, 7
• Aggressive intravenous hydration (2.5-3 liters/m²/day) titrated according to fluid balance and clinical status should be implemented immediately 2, 7
• Monitor for and prevent tumor lysis syndrome with allopurinol or rasburicase in high-risk patients 2, 7, 8

Cytoreduction Strategies

• The main goal of management is to reduce the white blood cell count before starting induction chemotherapy 3
• Cytoreduction can be achieved by:
  • Hydroxyurea (50-60 mg/kg/day) to rapidly reduce white blood cell counts 2, 7, 9
  • Leukapheresis in emergency organ-threatening conditions (cerebral or pulmonary leukostasis) 7, 3
  • Prompt initiation of definitive chemotherapy 1, 9

Special Considerations

• Avoid leukapheresis in Acute Promyelocytic Leukemia (APL) patients due to risk of precipitating fatal hemorrhage 7, 9
• Maintain platelet counts above 30-50 × 10^9/L and fibrinogen above 100-150 mg/dL to prevent hemorrhagic complications 7, 9
• Blood transfusions should be given with caution as they can significantly increase blood viscosity 8
• Avoid invasive procedures in patients with severe neutropenia due to risk of hemorrhagic complications 2, 7

Prognosis

• Patients with AML presenting with hyperleukocytosis have a particularly poor prognosis due to:
  • Higher risk of early death resulting from hyperleukocytosis complications
  • Higher probability of relapse and death in the long run 6
• Early mortality is primarily associated with renal and respiratory failure or intracranial hemorrhage 5

Treatment Algorithm

1. Immediate recognition and diagnosis of hyperleukocytosis (WBC >100,000/μL) 1, 3
2. Initiate aggressive hydration (2.5-3 L/m²/day) and monitor fluid balance 2, 7
3. Start hydroxyurea (50-60 mg/kg/day) for rapid cytoreduction 2, 7
4. Consider leukapheresis for symptomatic leukostasis (except in APL) 7, 3
5. Administer rasburicase or allopurinol to prevent tumor lysis syndrome 2, 7
6. Initiate definitive chemotherapy as soon as possible 1, 9, 5
7. Provide supportive care (platelet transfusions, coagulation factor replacement as needed) 7, 8