Can White Blood Cell (WBC) count be elevated secondary to cancer?

Can WBC Be Elevated Secondary to Cancer?

Yes, white blood cell (WBC) count can be significantly elevated as a direct consequence of cancer, occurring through multiple mechanisms including leukemic infiltration, paraneoplastic syndromes, and tumor-induced inflammatory responses.

Mechanisms of Cancer-Related Leukocytosis

Hematologic Malignancies

Leukemias directly cause elevated WBC counts through malignant proliferation of white blood cells:

• Acute lymphoblastic leukemia (ALL) commonly presents with elevated WBC counts, with levels ≥30 × 10⁹/L for B-cell lineage and ≥100 × 10⁹/L for T-cell lineage defining high-risk disease 1
• Acute promyelocytic leukemia (APL) frequently presents with hyperleukocytosis (WBC >10 × 10⁹/L), which requires immediate cytoreductive chemotherapy to prevent fatal hemorrhagic complications 1
• Acute myeloid leukemia (AML) patients with WBC >10,000/mm³ at presentation have worse prognosis and require risk-stratified treatment approaches 1

Paraneoplastic Leukocytosis in Solid Tumors

Solid malignancies can cause persistent leukocytosis through cytokine production:

• Urothelial carcinoma can present with paraneoplastic leukocytosis (WBC >20,000 cells/μL), which occurs in 0.6% of cases and confers extremely poor prognosis with median survival of only 71 days from leukocytosis onset 2
• This paraneoplastic syndrome is frequently associated with hypercalcemia, thrombocytosis, and anemia, and typically indicates muscle-invasive or metastatic disease 2
• Neither chemotherapy nor surgery provides durable WBC response, with rapid disease progression being the rule 2

Clinical Significance and Prognostic Implications

Thrombotic Risk

Elevated WBC counts in cancer patients substantially increase thromboembolism risk:

• Baseline leukocytosis (WBC >11 × 10⁹/L) in cancer patients initiating chemotherapy increases VTE risk 2.1-fold (HR 2.1,95% CI 1.3-3.4) 3
• Pre-cancer WBC counts measured years before cancer diagnosis predict future VTE risk in those who develop cancer (HR 2.36 for WBC ≥8.6 × 10⁹/L), suggesting a causal role rather than mere association 4
• Cancer patients with acute VTE and elevated WBC have increased recurrent VTE (OR 1.6), major bleeding (OR 1.5), and death (OR 2.7) 5

Mortality Risk

Leukocytosis independently predicts early mortality in cancer:

• Baseline leukocytosis in cancer patients starting chemotherapy increases early mortality risk 2.2-fold (HR 2.2,95% CI 1.5-3.3) 3
• Elevated WBC at recurrence diagnosis in cervical cancer patients reduces median survival to 9 months versus 21 months in those with normal counts 6
• The combination of leukocytosis and VTE confers the highest mortality risk 3

Management Considerations

Emergency Situations (Hyperleukocytosis)

When WBC exceeds 100,000/μL, immediate intervention is required:

• Aggressive IV hydration at 2.5-3 liters/m²/day prevents tumor lysis syndrome and maintains renal perfusion 7, 8
• Hydroxyurea 25-50 mg/kg/day (or 50-60 mg/kg/day in adults) provides rapid cytoreduction 7, 8
• Leukapheresis reduces WBC by 30-80% within hours but is reserved only for life-threatening organ compromise (cerebral or pulmonary leukostasis) 7

Critical Pitfall in APL

Never perform leukapheresis in acute promyelocytic leukemia due to risk of precipitating fatal hemorrhage 1, 7, 8. Instead:

• Start ATRA immediately upon suspicion, even before molecular confirmation 1, 8
• Maintain platelets >30-50 × 10⁹/L and fibrinogen >100-150 mg/dL 1, 8
• Add cytoreductive chemotherapy (idarubicin or daunorubicin) for hyperleukocytosis 1

Definitive Treatment Priority

Do not delay definitive chemotherapy while performing cytoreductive measures, as prompt initiation of cancer-directed therapy is essential for optimal outcomes 7, 8. The WBC elevation itself indicates aggressive disease biology requiring immediate treatment rather than prolonged supportive care alone.