Acute Leukemia

Aka: Acute Leukemia

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II. Precautions

  1. This topic covers a general approach to Acute Leukemia and its diagnosis
  2. See specific Acute Leukemia types for the most updated information

III. Types

  1. Acute Myelogenous Leukemia
    1. Most cases occur in adults
  2. Acute Lymphocytic Leukemia (or Acute Lymphoblastic Leukemia)
    1. Most cases (80%) occur in children (esp. age <5 years)
    2. Remaining 20% of Acute Lymphoblastic Leukemia cases occur in age >50 years old

IV. Findings: Signs and Symptoms (within 3 months of presentation)

  1. Anemia symptoms and signs
    1. Fatigue
    2. Dyspnea on exertion at even mild intensity
    3. Pallor
  2. Bleeding symptoms and signs
    1. Gingival Bleeding
    2. Gastrointestinal Bleeding
    3. Petechiae
    4. Easy bruisability
  3. Hematologic findings other than bleeding (rare in adults)
    1. Lymphadenopathy
    2. Splenomegaly
    3. Hepatomegaly
  4. Infectious symptoms and signs
    1. Fever
    2. Cellulitis
    3. Gingiva infection
    4. Candida infection
    5. Pneumonia
    6. Perirectal Abscess
    7. Urinary Tract Infection
  5. Chloroma development in any location
    1. Soft Tissue Masses of leukemic cells
  6. Expanding cell mass symptoms (50%)
    1. Bone pain (spine and long bones) is present in 43% of children
      1. Clarke (2016) Arch Dis Child 101(10):894-901 [PubMed]
    2. Sternal tenderness
  7. Renal related symptoms and signs
    1. Nephrolithiasis (Uric Acid stones)
    2. Urate nephropathy

V. Labs

  1. Complete Blood Count with differential (Pancytopenia)
    1. Leukocytosis or Leukopenia
    2. Anemia
    3. Thrombocytopenia
  2. Peripheral Smear
    1. Circulating blast cells may not be seen
  3. Chemistry panel (Chem 7)
    1. Hyponatremia
    2. Hypokalemia
    3. Hyperuricemia
  4. Liver Function Tests
    1. Lactate Dehydrogenase (LDH) increased

VI. Imaging

  1. Bone XRay
    1. Osteopenia
    2. Metaphyseal bands
    3. Lytic lesions
    4. Sclerotic changes
    5. Bone destruction

VII. Diagnosis

  1. General (both ALL and AML)
    1. Blast cell predominance
      1. However, blast cell absence on Peripheral Smear does not exclude Acute Leukemia
    2. Immunophenotyping (flow cytometry, cytogenetic testing) distinguishes between AML and ALL
  2. Acute Lymphoblastic Leukemia
    1. Lymphoblasts represent >20% of cells in Bone Marrow sample
    2. Also obtain Lumbar Puncture for CSF
  3. Acute Myelogenous Leukemia
    1. Myeloblasts represent >20% of cells in Bone Marrow or peripheral blood sample
    2. Auer rods on Peripheral Smear (not often found)
    3. Also obtain Lumbar Puncture for AML patients if undergoing intrathecal therapy

VIII. Management: Remission

  1. Goal
    1. Successive chemotherapeutic courses
      1. Each course results in fractional cell kill
    2. Results in up to 99.999 elimination of Leukemia cells
      1. Leukemia not detectable below 10^9 cells
    3. Some agents also Induce maturation of Leukemia cells
      1. Results in non-proliferating mature cells
  2. Criteria for Remission
    1. Less then 5 percent blast cells in Bone Marrow
    2. Leukemic cells absent in Bone Marrow
    3. Normal peripheral blood cell counts Restored
    4. Signs of extramedullary Leukemia involvement absent
  3. Overall Management Strategy
    1. Step 1: Remission Induction Chemotherapy
      1. Intensive systemic Chemotherapy
      2. Drives leukemic cell mass below detectable level
    2. Step 2: Early Intensification (Consolidation)
      1. Intensive Chemotherapy after Remission Induction
      2. Further reduce and possibly eradicate Leukemia
    3. Step 3: Maintenance
      1. Lower dose Chemotherapy continued over years
    4. Step 4: Late Intensification
      1. Intensive Chemotherapy restarted after 6 months
    5. Step 5: Local elimination of common relapse sites
      1. Local Chemotherapy or radiation to sanctuary sites

IX. Management: Supportive care of Pancytopenia

  1. Anemia
    1. Treat with packed Red Blood Cell Transfusion
  2. Thrombocytopenia
    1. Keep Platelet Count above 20 x 10^9/L
    2. Platelet Transfusion effective initially
    3. Antiplatelet Antibody develops over time
      1. Shortens Platelet survival
      2. Render patient unresponsive to transfusion
    4. May respond to HLA Identical Platelets
  3. Granulocytopenia (Neutropenia)
    1. Granulocyte transfusions not recommended
    2. Prevent infection
      1. Reverse isolation rooms
      2. Face Masks
      3. Careful Hand Washing
    3. Observation for Bacterial and fungal infection

X. Complications

  1. Leukostasis
    1. Occurs when circulating blasts > 100 x10^9/L
    2. Examples
      1. Lung hypoperfusion
      2. Brain hypoperfusion
  2. Thrombocytopenia related bleeding complications
    1. Occurs when Platelet Count < 20 x10^9/L
    2. Examples
      1. Gingival Bleeding
      2. Gastrointestinal Bleeding
  3. Neutropenia related infections
    1. Occurs when Neutrophil Count < 0.5 x10^9/L
    2. Examples
      1. Gram NegativeSepsis
      2. Candida infection

XI. References

  1. Davis (2014) Am Fam Physician 89(9): 731-8 [PubMed]
  2. Gbenjo (2023) Am Fam Physician 107(4): 397-405 [PubMed]

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