A 58-year-old man from Mumbai presents with a 6-month history of progressive fatigue and early satiety. On examination, he has marked splenomegaly (8 cm below costal margin) and mild hepatomegaly. Complete blood count shows: WBC 185,000/μL (85% neutrophils, 10% metamyelocytes, 5% myelocytes), Hb 8.2 g/dL, platelets 420,000/μL. Bone marrow aspirate shows myeloid predominance with left shift. Cytochemistry: LAP (leukocyte alkaline phosphatase) score is 15 (normal 20–100). Philadelphia chromosome is positive on karyotyping. What is the most likely diagnosis?

Question

Accepted Answer

A. Chronic myeloid leukemia in chronic phase. ## Diagnosis: Chronic Myeloid Leukemia (CML) in Chronic Phase ### Clinical Presentation **Key Point:** The constellation of marked splenomegaly, gradual onset fatigue, and massive leukocytosis with a left shift (but <30% blasts) in a middle-aged patient is pathognomonic for CML. ### Diagnostic Criteria Met | Feature | Finding | Significance | |---------|---------|---------------| | **WBC count** | 185,000/μL | Marked elevation; >50,000/μL typical in CML | | **Differential** | Left shift (metamyelocytes, myelocytes present) | Myeloid predominance with maturation | | **Blast percentage** | <5% | Chronic phase (if ≥20%, would be accelerated/blast crisis) | | **Splenomegaly** | 8 cm | Present in 90% of CML; extramedullary hematopoiesis | | **LAP score** | 15 (LOW) | **Hallmark of CML**—distinguishes from leukemoid reaction (LAP high) | | **Philadelphia chromosome** | **POSITIVE** | **Pathognomonic**—t(9;22) → BCR-ABL fusion gene | | **Platelets** | 420,000/μL | Often elevated in CML (thrombocytosis) | ### Pathophysiology **High-Yield:** The Philadelphia chromosome t(9;22) produces the BCR-ABL tyrosine kinase, which drives constitutive myeloid proliferation and suppresses apoptosis. This is the defining molecular lesion of CML. **Clinical Pearl:** LAP (leukocyte alkaline phosphatase) is LOW in CML because BCR-ABL-driven blasts have reduced enzyme activity. In contrast, leukemoid reactions (infection, inflammation) show HIGH LAP—this is the key discriminator. ### Phases of CML ```mermaid flowchart TD A[Philadelphia chromosome positive]:::outcome --> B{Blast percentage}:::decision B -->|<5% blasts| C[Chronic Phase]:::action B -->|5-30% blasts| D[Accelerated Phase]:::action B -->|≥30% blasts| E[Blast Crisis]:::urgent C --> F[Median survival: 5-6 years untreated
10+ years with TKI]:::outcome D --> G[Median survival: 6-12 months]:::outcome E --> H[Median survival: 3-6 months
Often AML or ALL phenotype]:::urgent ``` **Key Point:** This patient is in **chronic phase** (blasts <5%, LAP low, Ph+ present). ### Treatment **High-Yield:** First-line therapy is tyrosine kinase inhibitor (TKI): imatinib, dasatinib, or nilotinib. Imatinib (Gleevec) is the gold standard first-line agent, achieving complete hematologic remission in >95% of chronic-phase patients. [cite:Robbins 10e Ch 13] ![Chronic Leukemias diagram](https://mmcphlazjonnzmdysowq.supabase.co/storage/v1/object/public/blog-images/explanation/2638.webp)

Answer

B. Chronic neutrophilic leukemia

Answer

C. Acute myeloid leukemia

Answer

D. Myelodysplastic syndrome with excess blasts

Explanation

Diagnosis: Chronic Myeloid Leukemia (CML) in Chronic Phase

Clinical Presentation

Diagnostic Criteria Met

Pathophysiology

Phases of CML

Treatment

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Feature	Finding	Significance
WBC count	185,000/μL	Marked elevation; >50,000/μL typical in CML
Differential	Left shift (metamyelocytes, myelocytes present)	Myeloid predominance with maturation
Blast percentage	<5%	Chronic phase (if ≥20%, would be accelerated/blast crisis)
Splenomegaly	8 cm	Present in 90% of CML; extramedullary hematopoiesis
LAP score	15 (LOW)	Hallmark of CML—distinguishes from leukemoid reaction (LAP high)
Philadelphia chromosome	POSITIVE	Pathognomonic—t(9;22) → BCR-ABL fusion gene
Platelets	420,000/μL	Often elevated in CML (thrombocytosis)