Leukemias

Leukemias: Overview - Blood Cell Mayhem

• Malignant clonal proliferation of hematopoietic cells, primarily originating in bone marrow (BM) & peripheral blood.
• Leads to BM failure (anemia, thrombocytopenia, neutropenia) & potential organ infiltration.
• Key Classifications:
  • Acute vs. Chronic: Based on disease progression & cell maturity.
  • Myeloid vs. Lymphoid: Based on cell lineage involved (e.g., AML, CML, ALL, CLL).

⭐ Auer rods (eosinophilic, needle-like granules in cytoplasm) are pathognomonic for Acute Myeloid Leukemia (AML), especially M3 (APML).

Acute Leukemias: ALL/AML - Sudden Strike Squad

• Rapid proliferation of blasts (>20% in bone marrow). Sudden onset.
• ALL (Acute Lymphoblastic Leukemia):
  • Peak incidence: children (2-5 yrs). 📌 ALL kids get TdT+ toys.
  • Lymphoblasts: TdT+, PAS+. Often CALLA (CD10)+.
  • CNS involvement common; prophylaxis needed.
• AML (Acute Myeloid Leukemia):
  • Primarily adults (median age ~65 yrs).
  • Myeloblasts: MPO+, Sudan Black B+.
  • Auer rods (eosinophilic needles in cytoplasm) are pathognomonic.
  • DIC common in APL (M3 subtype, t(15;17)).
• Symptoms: Pancytopenia (fatigue, fever/infection, bleeding). Bone pain. Gingival hyperplasia (AML M4/M5).

⭐ Auer rods are pathognomonic for AML, representing fused lysosomal granules. Their presence excludes ALL.

CML: Pathophysiology & Phases - The Philly Story

• Pathophysiology
  • Genetic hallmark: Philadelphia chromosome (Ph+), from t(9;22)(q34;q11.2).
  • Forms BCR-ABL1 fusion gene → constitutively active tyrosine kinase.
  • Drives uncontrolled proliferation of myeloid cells, mainly granulocytes.
• Phases (WHO criteria)
  • Chronic Phase (CP): <10% blasts (blood/BM). Often asymptomatic. Best TKI response.
  • Accelerated Phase (AP): 10-19% blasts, OR ↑basophils ≥20%, OR persistent thrombocytopenia/thrombocytosis, OR new clonal chromosomal abnormalities (CCA).
  • Blast Crisis (BC): ≥20% blasts (myeloid/lymphoid). Resembles acute leukemia.

    ⭐ BCR-ABL1 tyrosine kinase is the target for TKIs (e.g., Imatinib), revolutionizing CML treatment.

and BCR-ABL1 fusion protein diagram)

CLL: Features & Staging - The Smudge Saga

• Most common leukemia in elderly Western adults; clonal mature B-cell (CD5+) proliferation.
• Presentation: Often asymptomatic. Lymphadenopathy, hepatosplenomegaly. B-symptoms less common.
• Diagnosis: Sustained absolute lymphocytosis >5000/μL. Smudge cells (Gumprecht shadows).
  • Immunophenotype: CD5+, CD19+, CD20+(dim), CD23+.
• Staging:
  • Rai (0-IV): Lymphocytosis, lymphadenopathy, organomegaly, anemia (Hb <11 g/dL), thrombocytopenia (<100,000/μL).
  • Binet (A,B,C): Based on # lymphoid areas, anemia, thrombocytopenia.

⭐ Richter's transformation: CLL transforms into aggressive large B-cell lymphoma (DLBCL) in ~5% cases, carrying a poor prognosis.

Leukemia: Complications & Dx - Red Alert & Clues

• Critical Complications (Red Alerts):
  • Tumor Lysis Syndrome (TLS):
    • Lab: ↑K, ↑$PO_4$, ↑Uric Acid, ↓Ca.
    • Rx: Hydration, Allopurinol/Rasburicase.
  • Neutropenic Fever:
    • Criteria: ANC < 500/mm³ + Fever > 38.3°C.
    • Rx: Empiric broad-spectrum antibiotics.
  • Hyperleukocytosis/Leukostasis:
    • WBC > 100,000/mm³ → sludging.
    • Sx: CNS, respiratory distress.
    • Rx: Hydration, Hydroxyurea, Leukapheresis.
• Key Diagnostic Clues:
  • Peripheral Smear: Blasts ± Auer rods (AML).
  • Bone Marrow Exam: Definitive Dx; cytogenetics, immunophenotyping (flow cytometry).
  • Cytogenetics/FISH: Specific translocations (e.g., t(9;22) CML; t(15;17) APML).

⭐ Auer rods, eosinophilic needle-like granules in myeloblast cytoplasm, are pathognomonic for Acute Myeloid Leukemia (AML).

High‑Yield Points - ⚡ Biggest Takeaways

• Auer rods: Pathognomonic for AML, especially M3 (APL).
• APL (M3): t(15;17) translocation, treat with ATRA; risk of DIC.
• CML: Philadelphia chromosome t(9;22) (BCR-ABL1); responds to Imatinib.
• CLL: Most common adult leukemia (West); smudge cells on smear.
• ALL: Most common childhood cancer; CNS prophylaxis is mandatory.
• Richter's transformation: CLL converts to aggressive lymphoma (e.g., DLBCL).
• LAP score: High in Leukemoid reaction, low/absent in CML.