Does Chronic Myeloid Leukemia (CML) cause a rising White Blood Cell (WBC) count?

Chronic Myeloid Leukemia and White Blood Cell Count

Yes, Chronic Myeloid Leukemia (CML) characteristically causes a rising white blood cell (WBC) count, often exceeding 100 x 10^9/L, as a hallmark feature of the disease. 1

Pathophysiology of Elevated WBC in CML

• CML is characterized by hypercellular bone marrow and unregulated growth of myeloid cells resulting in abnormally high levels of differentiated granulocytes and granulocytic precursor cells in the blood 1
• The Philadelphia chromosome, created by a reciprocal translocation between chromosomes 9 and 22 [t(9;22)(q34;q11)], produces the BCR-ABL fusion gene that drives the disease 2
• This constitutively activated tyrosine kinase leads to excessive proliferation of the myeloid cell line, causing:
  • Markedly elevated WBC counts (can range from 100-600 x 10^9/L) 3
  • "Pathological shift to the left" (increased immature granulocytic precursors) 1

Clinical Presentation and Diagnosis

• About 50% of patients with CML in Europe are asymptomatic at diagnosis, with the disease frequently discovered after routine blood tests 1

• When symptomatic, common presentations include:

  • Fatigue, weight loss, malaise (from anemia and splenomegaly)
  • Left upper quadrant fullness or pain (from splenomegaly)
  • Splenomegaly (most consistent physical sign, detected in 40-50% of cases) 1

• Laboratory findings typically include:

  • High WBC count (often >100 x 10^9/L)
  • Mild anemia
  • Normal or elevated platelet count 1

WBC Count in Different Phases of CML

CML progresses through three distinct phases, with WBC characteristics in each:

1. Chronic Phase (CP):

   • Most patients (90-95%) present in this phase 1
   • Characterized by high WBC counts with mature and immature granulocytes
   • <10-15% blasts in blood or bone marrow (depending on classification system) 1

2. Accelerated Phase (AP):

   • One criterion for AP is "persisting or increasing WBC count (>10 x 10^9/L) unresponsive to therapy" 1
   • Blast percentage increases to 10-29% (varies by classification system)

   • 20% basophils in peripheral blood 1

3. Blast Phase/Crisis (BP):

   • Characterized by ≥20-30% blasts in blood or bone marrow (depending on classification system)
   • Resembles acute leukemia 2

Prognostic Significance of WBC Count

• High initial WBC count (>150 x 10^9/L) is associated with poorer outcomes:

  • Lower rates of achieving deep molecular responses to treatment 4
  • Poorer event-free survival, progression-free survival, and overall survival 4

• WBC count is included in prognostic scoring systems for CML:

  • The Sokal score includes blood blast percentage 1
  • The EUTOS score incorporates spleen size and basophil percentage, which correlate with disease burden 1

Treatment Response Assessment

• Complete hematologic response is defined as:

  • WBC <10 x 10^9/L
  • Platelet count <450 x 10^9/L
  • No immature granulocytes in the differential
  • Non-palpable spleen 1, 5

• Monitoring treatment response requires regular complete blood counts with differential until complete hematologic response is achieved 1

Clinical Pitfalls and Caveats

• Despite very high WBC counts, leukostatic symptoms (priapism, dyspnea, drowsiness, confusion) are uncommon in chronic phase CML 1
• Rarely, some patients may exhibit cyclic patterns of leukocytosis-leukopenia 6
• Not all rising WBC counts in CML patients indicate disease progression - infections or medication effects should be considered
• In patients on tyrosine kinase inhibitor (TKI) therapy, a rising WBC count may indicate treatment failure or disease progression 5

The introduction of TKIs has dramatically altered the natural history of CML, with high rates of progression-free and overall survival when treatment is initiated promptly after diagnosis 2, 5.