What is the management and treatment of leukocytosis (elevated White Blood Cell (WBC) count)?

Management of Leukocytosis

The management of leukocytosis should be directed at the underlying cause, with immediate aggressive intervention required for hyperleukocytosis (WBC >100 × 10⁹/L) due to the risk of leukostasis, tumor lysis syndrome, and potentially fatal complications. 1, 2

Initial Assessment and Management Based on Severity

Mild to Moderate Leukocytosis

• Identify and treat the underlying cause, which is commonly infection, inflammation, medication effect, or stress 3, 4
• Common medication causes include corticosteroids, lithium, and beta agonists 3
• Consider non-malignant causes such as smoking, obesity, asplenia, and chronic inflammatory conditions 5

Severe Leukocytosis (Hyperleukocytosis >100 × 10⁹/L)

• Implement immediate aggressive intravenous hydration (2.5-3 liters/m²/day) titrated according to fluid balance and clinical status 6, 2
• Initiate hydroxyurea (25-50 mg/kg/day in 2-3 divided doses) to rapidly reduce WBC counts 6
• Monitor for and prevent tumor lysis syndrome; allopurinol is required only in cases with deranged TLS parameters 6, 2
• For emergency organ-threatening conditions (cerebral or pulmonary leukostasis, priapism), consider leukapheresis or exchange transfusion for faster cytoreduction 6, 2

Management Based on Underlying Etiology

Leukemia-Associated Leukocytosis

• Start definitive therapy once diagnosis is confirmed 1, 5
• For chronic myeloid leukemia (CML):
  • Start tyrosine kinase inhibitors (TKIs) once Philadelphia chromosome or BCR::ABL1 fusion gene is detected 6
  • TKIs typically reduce WBC count by 50% within 1-2 weeks 6
• For acute myeloid leukemia (AML):
  • Consider cytarabine-based regimens for faster cytoreduction 6
  • Low-dose cytarabine (100 mg/m²/day IV) can reduce WBC count by 50% within 3-5 days 6
• For acute promyelocytic leukemia (APL):
  • AVOID leukapheresis due to risk of fatal hemorrhage 6, 2
  • Start ATRA immediately once APL is suspected 6
  • Add chemotherapy without delay for patients with WBC >10 × 10⁹/L 6

Management of Complications

Leukostasis

• Monitor for signs of organ dysfunction, particularly pulmonary and neurological symptoms 6, 2
• Despite high WBC counts in children (median 240,000/μL), leukostasis is an infrequent complication in pediatric CML-CP 6
• For symptomatic leukostasis, consider faster-acting cytoreductive measures 6, 2

Tumor Lysis Syndrome

• Maintain aggressive hydration 6
• Monitor electrolytes closely and correct abnormalities 2
• Consider rasburicase in high-risk patients 5

Special Considerations

• Avoid invasive procedures such as central venous catheterization, lumbar puncture, and bronchoscopy in patients with active coagulopathy 6, 2
• WBC counts above 100,000/μL represent a medical emergency due to the risk of brain infarction and hemorrhage 3
• Mortality increases significantly as WBC counts rise above 40 × 10⁹/L (from 2.8% to 33%) 7
• In patients with myeloproliferative disorders, leukocytosis may be an independent risk factor for thrombotic events 8

Speed of Leukoreduction by Treatment Modality

• Hydroxyurea (50 mg/kg/day): 50% reduction within 1-2 weeks 6
• Tyrosine kinase inhibitors: 50% reduction within 1-2 weeks 6
• Low-dose cytarabine (100 mg/m²/day IV): 50% reduction within 3-5 days 6
• Low-dose cytarabine plus thioguanine: 50% reduction within 3 days 6
• Leukapheresis/exchange transfusion: 30-80% reduction within hours 6, 2