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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). Normal vs. Leukemia Blood Cells

⭐ 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.

ALL vs AML Leukemic Cells

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.

Philadelphia chromosome formation 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.

Practice Questions: Leukemias

Test your understanding with these related questions

In the evaluation of a newly diagnosed case of acute lymphoid leukemia (ALL), which of the following tests is not routinely included?

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Flashcards: Leukemias

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NPM1 and CEBPA mutation is associated with a _____ prognosis in patients with acute myeloid leukemia (AML).

TAP TO REVEAL ANSWER

NPM1 and CEBPA mutation is associated with a _____ prognosis in patients with acute myeloid leukemia (AML).

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