What is the initial management of leukocytosis (elevated white blood cell count)?

Initial Management of Leukocytosis

For severe leukocytosis (WBC >100,000/μL), immediately initiate aggressive IV hydration at 2.5-3 liters/m²/day and start hydroxyurea 50-60 mg/kg/day for cytoreduction, while simultaneously working up the underlying cause. 1, 2

Immediate Assessment and Risk Stratification

Determine urgency based on WBC count and symptoms:

• WBC >100,000/μL represents hyperleukocytosis and constitutes a medical emergency due to risk of leukostasis, brain infarction, and hemorrhage 3, 2, 4
• Assess for leukostasis symptoms: respiratory distress (pulmonary infiltrates), neurologic changes (cerebral hemorrhage/infarction), or visual changes (retinal hemorrhage) 3
• Obtain complete blood count with differential to evaluate all cell lines, as concurrent anemia and thrombocytopenia suggest malignancy 2
• Review peripheral blood smear immediately—never assume malignancy without smear review, as reactive leukocytosis from infection is far more common 2, 5

Emergency Cytoreduction (for Hyperleukocytosis)

Initiate cytoreduction immediately without waiting for definitive diagnosis if WBC >100,000/μL: 2

• Start hydroxyurea 50-60 mg/kg/day to rapidly reduce WBC counts to <10-20 × 10⁹/L 3, 1, 2
• Aggressive IV hydration: 2.5-3 liters/m²/day, titrated to fluid balance and clinical status 1, 2
• Tumor lysis syndrome prophylaxis: Allopurinol or rasburicase in high-risk patients 3, 1, 2
• Monitor electrolytes closely (uric acid, potassium, phosphorus, calcium, renal function) 1, 2

Critical pitfall: Avoid excessive red blood cell transfusions until WBC is reduced, as this increases blood viscosity and worsens leukostasis 3

Leukapheresis Considerations

Leukapheresis is an option for organ-threatening leukostasis (cerebral or pulmonary symptoms), but has no proven impact on long-term outcomes: 3, 1

• Consider only for emergency situations with symptomatic leukostasis 3
• Never perform leukapheresis in acute promyelocytic leukemia (APL) due to catastrophic hemorrhage risk 1, 2

Diagnostic Workup (Parallel to Cytoreduction)

If acute leukemia is suspected based on smear or clinical presentation:

• Obtain bone marrow aspiration and biopsy immediately before starting definitive chemotherapy (but after cytoreduction is initiated) 3, 2
• Blood cultures and infection workup if febrile or infection suspected 1, 2
• Coagulation studies (PT, PTT, fibrinogen, D-dimer) to detect leukemia-related coagulopathy, especially if APL suspected 3
• HLA typing of patient and family members if allogeneic transplant candidate 3

Treatment can be safely delayed several days until molecular typing is complete in stable patients, but never delay hydration and cytoreduction 2

Supportive Care During Initial Management

Maintain hemostasis and prevent complications:

• Keep platelet counts >30-50 × 10⁹/L and fibrinogen >100-150 mg/dL 1
• Avoid invasive procedures (central lines) in severe neutropenia due to hemorrhage risk 1
• Obtain blood cultures before antibiotics if infection suspected 1, 2
• Empirical broad-spectrum antibiotics for febrile neutropenia 2
• Consider fluoroquinolone prophylaxis if prolonged profound granulocytopenia expected 2

Special Considerations for APL

If APL is suspected or cannot be excluded:

• Start all-trans retinoic acid (ATRA) immediately, only discontinue when APL is specifically excluded 3, 2
• Monitor closely for coagulopathy and differentiation syndrome 3
• Avoid leukapheresis due to fatal hemorrhage risk 1, 2

Common Pitfalls to Avoid

• Never delay hydration and cytoreduction while awaiting definitive diagnosis if hyperleukocytosis is present 2
• Never assume malignancy without peripheral smear review—infection and inflammation are far more common causes 2, 5
• Avoid azole antifungals during anthracycline chemotherapy due to drug interactions increasing toxicity 1
• Do not use absolute lymphocyte count alone as treatment indicator in chronic lymphocytic leukemia, as symptoms from leukocyte aggregates rarely occur 3