What is the diagnosis and management for a patient with anemia (low hematocrit), normal platelet count, thrombocytopenia with low mean platelet volume, eosinophilia (elevated absolute eosinophil count), basophilia (elevated absolute basophil count), and a normal white blood cell count?

Chronic Myeloid Leukemia (CML) in Chronic Phase

This patient most likely has chronic myeloid leukemia (CML) in chronic phase, and requires immediate BCR-ABL testing (cytogenetics and qualitative RT-PCR) followed by tyrosine kinase inhibitor therapy with imatinib as first-line treatment. 1

Diagnostic Reasoning

Key Laboratory Pattern Recognition

The combination of basophilia and eosinophilia with normal WBC count is highly characteristic of CML, even when the white count appears normal. 1 This pattern occurs because:

• Basophilia is common in CML and appears in the risk stratification systems (EURO and EUTOS scores use basophil percentage as prognostic factors). 1
• Eosinophils may be prominent in CML at diagnosis. 1
• The anemia (low hematocrit) reflects the typical presentation where 50% of European CML patients are asymptomatic but show laboratory abnormalities including anemia from bone marrow dysfunction. 1

Critical Distinction from Other Conditions

The low mean platelet volume with normal platelet count helps differentiate this from:

• Myeloproliferative disorders with thrombocytosis typically show high or normal MPV. 2
• Myelodysplastic syndrome (MDS) can present with basophilia and eosinophilia but usually shows thrombocytopenia or other cytopenias, not normal platelet counts. 3
• Essential thrombocythemia would show elevated platelet counts. 1

Immediate Diagnostic Workup Required

Mandatory Baseline Tests (Before Any Treatment)

1. Bone marrow aspiration with cytogenetics to detect t(9;22)(q34;q11) Philadelphia chromosome. 1
2. Qualitative RT-PCR on peripheral blood to identify BCR-ABL transcript type (e14a2 or e13a2). 1
3. Complete blood count with differential every 15 days until complete hematologic response achieved. 1

Tests NOT Required at Baseline

• Quantitative RT-PCR (qRT-PCR) is not needed at diagnosis but will be essential for monitoring response every 3 months after treatment starts. 1
• Interphase FISH is only needed if cytogenetics cannot be analyzed or is normal. 1

Risk Stratification

Calculate the EUTOS score (simpler and more accurate for imatinib-treated patients than older Sokal or EURO scores): 1

• (4 × spleen size in cm below costal margin) + (7 × basophil percentage)
• Low risk: ≤87
• High risk: >87

This score determines prognosis and may influence monitoring intensity. 1

Treatment Algorithm

First-Line Therapy

Imatinib remains the gold standard first-line treatment worldwide. 1

• Start after confirming BCR-ABL positivity
• If marked leukocytosis present (not in this case with normal WBC), use hydroxyurea for short pretreatment phase only. 1
• Never use busulfan (historical agent no longer appropriate). 1

Monitoring Response

Assess response at specific timepoints: 1

• 3 and 6 months: Bone marrow karyotype
• Every 3 months: Quantitative RT-PCR on peripheral blood
• Every 15 days initially: Complete blood counts until stable complete hematologic response

Definition of Adequate Response

Complete hematologic response requires: 1

• WBC <10 × 10⁹/L
• Platelet count <450 × 10⁹/L
• No immature granulocytes in differential
• Spleen non-palpable

Critical Pitfalls to Avoid

Do Not Dismiss Normal WBC Count

CML can present with normal white blood cell counts. 1 The diagnostic clue is the combination of basophilia, eosinophilia, and anemia, not the absolute WBC number. Many clinicians incorrectly assume CML always presents with marked leukocytosis. 1

Do Not Delay BCR-ABL Testing

The Philadelphia chromosome and BCR-ABL transcripts are required for definitive diagnosis. 1 Clinical suspicion alone is insufficient to start therapy, but testing should be expedited as CML is a progressive disease.

Do Not Confuse with Reactive Conditions

Reactive eosinophilia and basophilia from allergic, parasitic, or inflammatory conditions would not typically cause anemia or the specific hematologic pattern seen here. 4 The combination of findings points to a clonal myeloproliferative process. 1

Monitor for Transformation

Without treatment, CML progresses to accelerated phase (15-29% blasts) or blast phase (≥30% blasts). 1 Early diagnosis and treatment with tyrosine kinase inhibitors prevents this progression in most patients. 1