A 58-year-old Indian man presents with a 6-month history of progressive fatigue and left upper quadrant fullness. On examination, the spleen is palpable 8 cm below the costal margin. Complete blood count reveals hemoglobin 9.2 g/dL, WBC 185,000/μL with left shift, and platelets 420,000/μL. Peripheral blood smear shows myelocytes, metamyelocytes, and occasional blasts (3%). Bone marrow aspirate shows hypercellularity with myeloid predominance and <5% blasts. Cytochemistry shows positive myeloperoxidase (MPO) and negative periodic acid–Schiff (PAS). Philadelphia chromosome is positive on cytogenetics. What is the most likely diagnosis?

Explanation

## Diagnosis: Chronic Myeloid Leukemia (CML) in Chronic Phase ### Clinical Presentation **Key Point:** CML typically presents with insidious onset of fatigue, weight loss, and splenomegaly in middle-aged to older adults. The 6-month progressive course is typical of chronic phase disease. ### Diagnostic Criteria Met | Feature | Finding | Significance | |---------|---------|---------------| | **WBC count** | 185,000/μL | Marked leukocytosis with left shift | | **Blasts** | <5% in blood and marrow | Defines chronic phase (not accelerated or blast crisis) | | **Myeloid maturation** | Myelocytes, metamyelocytes present | Preserved myeloid differentiation | | **Philadelphia chromosome** | Positive (t(9;22)) | Pathognomonic for CML | | **Splenomegaly** | 8 cm below costal margin | Present in ~90% of CML at diagnosis | | **Platelet count** | 420,000/μL | Often elevated in early CML | ### Pathophysiology **High-Yield:** The t(9;22) translocation creates the BCR-ABL1 fusion gene, which produces a constitutively active tyrosine kinase. This drives uncontrolled myeloid proliferation while maintaining differentiation capacity — hence the "left shift" with preserved maturation. **Mnemonic:** **CML = Chronic + Myeloid + Left shift + Splenomegaly + Philadelphia chromosome** — all present here. ### Why Chronic Phase? 1. Blasts <5% (accelerated phase: 5–19%; blast crisis: ≥20%) 2. No basophilia >20% or eosinophilia >10% 3. Platelet count not <100,000/μL 4. No extramedullary involvement beyond splenomegaly ### Cytochemistry Interpretation - **MPO positive:** Confirms myeloid lineage - **PAS negative:** Rules out erythroleukemia or some ALL variants **Clinical Pearl:** CML is now managed with tyrosine kinase inhibitors (TKIs: imatinib, dasatinib, nilotinib). Patients in chronic phase on TKI therapy have near-normal life expectancy if they achieve and maintain BCR-ABL1 transcript suppression. [cite:Robbins 10e Ch 13]