What are the typical lab values in a patient with Chronic Myeloid Leukemia (CML) in the chronic phase?

Laboratory Values in Chronic Myeloid Leukemia - Chronic Phase

Chronic phase CML typically presents with marked leukocytosis (often >25,000/µL and frequently >100,000/µL), left-shifted granulocytosis with immature forms from metamyelocytes to myeloblasts, basophilia, thrombocytosis, and mild anemia. 1, 2

Complete Blood Count Findings

White Blood Cell Parameters

• Leukocytosis is the hallmark finding, with WBC counts frequently exceeding 100 × 10⁹/L 2
• Left shift with immature granulocytes visible at all stages of maturation, ranging from metamyelocytes to myeloblasts 1, 2
• Blast percentage <10-15% in peripheral blood and bone marrow defines chronic phase (WHO criteria use <10%, European LeukemiaNet uses <15%) 1, 3, 4
• Basophilia is characteristic, with absolute basophil counts ≥200/mm³ helping distinguish CML from reactive leukocytosis 2, 5
• Basophils may comprise a significant percentage of the differential, though <20% (≥20% indicates accelerated phase) 1, 3, 6
• Eosinophilia may be prominent in some cases 2

Platelet Count

• Thrombocytosis is frequently present at diagnosis and is a characteristic feature 1, 2
• Platelet counts are typically normal or elevated in chronic phase 1, 2
• Despite normal/elevated counts, 20% of pediatric patients may present with bleeding signs due to platelet dysfunction 2

Hemoglobin/Hematocrit

• Mild anemia is common at presentation 1, 2
• Anemia is considered a characteristic feature but is typically not severe in chronic phase 2

Bone Marrow Findings

Cellularity and Morphology

• Hypercellular bone marrow with unregulated growth of myeloid cells 1
• Increased cellularity due to proliferation of myelopoiesis at all stages 1, 6
• Blast percentage <10-15% in bone marrow (depending on classification system used) 1, 3, 4
• Morphologic dysplasia is typically not present in chronic phase 7

Megakaryocyte Abnormalities

• Small, hypolobated megakaryocytes are characteristic 5
• In preleukemic CML, approximately 40% of megakaryocytes show this morphology, compared to 86% in established CML-CP 5

Microvascular Changes

• Increased microvascular density (approximately 10-12.5 vessels per 200× field) 5
• Tortuous microvessels with abnormal branching patterns, highlighted by CD34 immunostaining 5

Biochemical Parameters

Typically Normal in Chronic Phase

• Liver enzymes (SGPT/ALT, SGOT/AST) are usually normal 1
• Bilirubin is typically normal 1
• Creatinine is usually normal 1
• Electrolytes (calcium, potassium, phosphate) are generally normal at diagnosis 1

Important Note on Biochemical Abnormalities

Grade 3/4 biochemical abnormalities (hypocalcemia, hypokalemia, hypophosphatemia, elevated transaminases) occur with increased frequency in accelerated or blast phase, not chronic phase 8

Cytogenetic and Molecular Confirmation

Required for Diagnosis

• Philadelphia chromosome t(9;22)(q34;q11.2) detected by conventional cytogenetics in 95% of cases 1
• BCR-ABL1 fusion gene detected by FISH or RT-PCR in all cases, including the 5% without visible Ph chromosome 1
• Median BCR-ABL1 level at diagnosis is approximately 26% 9
• Additional cytogenetic abnormalities at baseline may indicate higher risk but do not exclude chronic phase 1

Clinical Correlates

Physical Examination Findings

• Splenomegaly present in >50% of cases at diagnosis 1
• 40-50% of patients are asymptomatic at presentation 1
• Symptoms when present include fatigue (46%), weight loss (25%), fever, and abdominal pain (23%) 1

Critical Pitfalls to Avoid

Aleukemic Presentation

Be aware that rare cases of "aleukemic" or "preleukemic" CML exist with normal or only mildly elevated WBC (3.6-14.3 K/mm³) but still harbor BCR-ABL1. 9, 7, 5 These cases are frequently misdiagnosed or diagnosis is delayed (45% in one series) 9. Key clues include:

• Absolute basophilia ≥200/mm³ even with normal WBC 5
• Presence of rare myelocytes (1-2%) on differential 7
• Increased microvascular density and small hypolobated megakaryocytes on bone marrow biopsy 5
• History of prior or concurrent malignancies (present in 55% of aleukemic cases) 9

Distinguishing from Leukemoid Reaction

• Basophilia, left shift, and characteristic cytogenetics are equally important diagnostic features, not just blast percentage 2
• Microvascular density in leukemoid reaction is approximately half that of CML (5.0 vs 10.0 vessels/200× field) 5
• Small hypolobated megakaryocytes comprise only 13% in leukemoid reaction versus 40% in preleukemic CML 5

Bleeding Risk Assessment

Normal or elevated platelet counts do not exclude bleeding risk, as functional platelet abnormalities are common in CML 2