Chronic Leukemias

Chronic Leukemias Overview - The Slow Burn

• Insidious onset, primarily affecting older adults.
• Clonal proliferation of more mature-appearing hematopoietic cells.
• Slower progression compared to acute leukemias; often indolent course.
• Frequently discovered incidentally during routine blood work.
• Common features: fatigue, weight loss, splenomegaly, cytopenias (later stages).
• Peripheral blood often shows ↑ specific mature cells.
• Bone marrow is typically hypercellular with lineage-specific proliferation.

⭐ Chronic leukemias are generally insidious in onset and affect older adults, characterized by proliferation of more mature hematopoietic cells.

Chronic Myeloid Leukemia (CML) - Philly's Fatal Fusion

• Myeloproliferative neoplasm (MPN); clonal stem cell disorder.
• 📌 CML = City of Philadelphia, 9:22 PM; t(9;22) (BCR-ABL1 fusion gene).
• Pathophysiology: Constitutively active tyrosine kinase → uncontrolled cell proliferation.
• Key Features:
  • Insidious: fatigue, weight loss, splenomegaly.
  • Blood: ↑WBC (marked left shift), basophilia, eosinophilia, often thrombocytosis. Low LAP score.
• Phases:

-   Chronic: <**10%** blasts.
-   Accelerated: **10-19%** blasts, ↑basophils >**20%**, worsening splenomegaly.
-   Blast Crisis: ≥**20%** blasts (myeloid/lymphoid).

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• Diagnosis: Bone marrow: hypercellular. Cytogenetics/FISH/PCR for BCR-ABL1.

⭐ The Philadelphia chromosome t(9;22)(q34;q11.2) resulting in the BCR-ABL1 fusion gene is the pathognomonic hallmark of CML.

• Treatment: Tyrosine Kinase Inhibitors (TKIs) like Imatinib.

Chronic Lymphocytic Leukemia (CLL/SLL) - The Lymphocyte Flood

• Most common adult leukemia (West); indolent B-cell neoplasm. SLL: tissue form.

• Patho: Accumulation of clonal, mature but immunoincompetent B-cells.

• Diagnosis: Absolute lymphocytosis >5000/μL (peripheral blood).

  • Smear: Small, mature lymphocytes; smudge cells (Gumprecht shadows).

• Immunophenotype: CD19+, CD20+(dim), CD5+, CD23+. Surface Ig (dim).

• Clinical: Often asymptomatic. Fatigue, lymphadenopathy, hepatosplenomegaly. B-symptoms less common.

• Complications:

  • Infections (hypogammaglobulinemia).
  • Autoimmune cytopenias (AIHA, ITP).
  • Richter's Transformation (to DLBCL, ~2-10%).

• Staging (Rai Simplified):

⭐ Characteristic immunophenotype for CLL is CD19+, CD20+ (dim), CD5+, and CD23+; smudge cells (crushed lymphocytes) are frequently seen on peripheral blood smears.

Hairy Cell Leukemia (HCL) - Trap 'Em Hairs

• Rare, indolent B-cell neoplasm; M:F 4:1.
• Pathogenesis: BRAF V600E mutation (>90%).
• Clinical:
  • Pancytopenia.
  • Massive splenomegaly.
  • No lymphadenopathy (usually).
  • ↑ Susceptibility to atypical mycobacterial infections.
• Morphology:
  • Peripheral blood: "Hairy cells" (lymphocytes with fine, circumferential cytoplasmic projections). Monocytopenia is characteristic.
  • Bone marrow: "Fried egg" appearance of cells; dry tap on aspiration due to marrow fibrosis (reticulin).
• Key Test:
  • 📌 TRAP positive (Tartrate Resistant Acid Phosphatase).
• Immunophenotype: Pan B-cell markers (CD19, CD20, CD22); specific: CD11c, CD25, CD103, Annexin A1.

⭐ Hairy Cell Leukemia is characterized by pancytopenia, massive splenomegaly, 'hairy' B-lymphocytes in peripheral blood/bone marrow, and strong positivity for TRAP stain; BRAF V600E mutation is highly prevalent.

• Rx: Cladribine (2-CdA), Pentostatin. Excellent prognosis with therapy.

High‑Yield Points - ⚡ Biggest Takeaways

• CML: Philadelphia t(9;22), BCR-ABL1; TKIs; low LAP score.
• CLL: Most common adult leukemia; CD5+/CD23+ B-cells, smudge cells; Richter's transformation.
• Hairy Cell Leukemia: BRAF V600E; TRAP positive; "hairy" cells, pancytopenia; cladribine.
• Polycythemia Vera: JAK2 V617F (>90%); ↑RBC mass, low EPO; aquagenic pruritus.
• Essential Thrombocythemia: JAK2/CALR/MPL mutations; marked thrombocytosis; thrombotic/hemorrhagic risk.
• Primary Myelofibrosis: JAK2/CALR/MPL mutations; marrow fibrosis, teardrop RBCs; massive splenomegaly.