II. Epidemiology

  1. Incidence
    1. Annual Incidence: 13 per 100,000 people per year
    2. Lifetime Incidence: 1 in 70 people
  2. Higher Incidence in men
  3. Age distribution
    1. All Ages
      1. Acute Myelogenous Leukemia (AML)
    2. Young
      1. Acute Lymphocytic Leukemia (ALL)
    3. Elderly
      1. Chronic Lymphocytic Leukemia
      2. Hairy Cell Leukemia

IV. Pathophysiology

  1. Malignant neoplasm of hematopoietic origin
  2. Origins
    1. Myeloid (Bone Marrow)
    2. Lymphoid
  3. Acute (Proliferating cell fails to mature past blast)
    1. AML: Immature clonal myeloid Cells (Myeloblast)
    2. ALL: Immature clonal lymphoid Cells (Lymphoblast)

V. Risk Factors

  1. Idiopathic
  2. Demographics and habitus
    1. White
    2. Male
    3. Obesity
  3. Human T-Cell Leukemia Virus (HTLV-1)
  4. History of Hematologic Malignancy
  5. Congenital syndrome (risk of childhood ALL, AML)
    1. Down's Syndrome
    2. Neurofibromatosis
    3. Bloom's Syndrome
    4. Klinefelter's Syndrome
    5. Fanconi's Syndrome
    6. Wiskott-Aldrich Syndrome
  6. Environmental Factors
    1. Ionizing Radiation exposure (risk of CML, AML, ALL)
      1. Atomic bomb survivors
      2. Medical radiation workers prior to 1950
      3. Medical radiation patients
    2. Chemical exposure (risk of AML)
      1. Aromatic Hydrocarbons (e.g. Benzene)
        1. Manufacturing of paints, plastics
        2. Petroleum or coal combustion
      2. Alkylating Agents
      3. Chemotherapeutic drugs

VI. Labs: Initial

  1. Complete Blood Count
    1. Acute Leukemia
      1. Leukocytosis or Leukopenia
      2. Anemia
      3. Thrombocytopenia
    2. Chronic Leukemias
      1. Leukocytosis >20,000/mm3 in most cases (often >100,000/mm3)
  2. Other initial lab tests
    1. Coagulation studies
      1. ProTime (INR)
      2. Partial Thromboplastin Time (PTT)
    2. Comprehensive metabolic panel
      1. Serum Electrolytes
      2. Renal Function tests including Serum Creatinine
      3. Liver Function Tests
  3. Patient febrile or otherwise ill appearing
    1. Urinalysis
    2. Urine Culture
    3. Blood Culture
    4. Chest XRay

VII. Labs: Diagnosis

  1. Studies
    1. Peripheral Blood Smear
    2. Bone Marrow Biopsy
  2. Acute Leukemia findings
    1. Blast cell predominance
    2. Auer rods on Peripheral Smear (AML, not often found)
    3. Immunophenotyping (flow cytometry, cytogenetic testing) distinguishes between AML and ALL
  3. Chronic Lymphocytic Leukemia findings
    1. Significant increase of normal appearing Lymphocytes (>50% of cells)
    2. Peripheral blood for clonal expansion of B Lymphocytes >5000/mm3
    3. Bone Marrow Biopsy is not needed for diagnosis (but defines extent of marrow involvement related to prognosis)
  4. Chronic Myelogenous Leukemia
    1. Peripheral Smear with few blast cells and increased Basophils and Eosinophils
    2. Philadelphia Chromosome (BCR-ABL1 fusion gene) on peripheral blood or Bone Marrow testing

VIII. Evaluation

  1. Step 0: Leukocytosis (White Blood Cell Count >11,000/mm3)
    1. Confirmed with a second Complete Blood Count with differential
    2. No other obvious cause for Leukocytosis (e.g. infection, Corticosteroids)
  2. Step 1: Consider secondary causes based on white cell count differential
    1. Monocyte predominance (monocytosis)
      1. Consider chronic infection (e.g. Tuberculosis, parasitic infectikon)
      2. Consider Connective Tissue Disease (e.g. Sarcoidosis, Inflammatory Bowel Disease)
    2. Eosinophil predominance (Eosinophilia)
      1. Consider allergic condition (e.g. Allergic Rhinitis, atopy, Asthma)
      2. Consider Parasite infection
      3. Consider Collagen vascular disease
        1. Examples: Rheumatoid Arthritis, Systemic Lupus Erythematosus, Sarcoidosis, Addison's Disease
      4. Consider medication causes (e.g. Methotrexate, Sulfonamides, Nitrofurantoin)
    3. Neutrophil predominance (Neutrophilia)
      1. Consider infection or inflammation
      2. Consider medication causes (e.g. Corticosteroids, Lithium, beta Agonists)
      3. Consider aspenia or Splenic Sequestration
    4. Lymphocyte predominance (Lymphocytosis)
      1. Consider infections (e.g. EBV, CMV, Pertussis, Tuberculosis)
      2. Consider Asplenia or Splenic Sequestration
    5. Basophil predominance (Basophilia, rare)
      1. Consider Asplenia
      2. Consider Hypothyroidism
      3. Consider chronic inflammation (e.g. Inflammatory Bowel Disease, Chronic Sinusitis, Asthma)
  3. Step 2: Indications to proceed with Peripheral Smear
    1. Leukocytosis without other secondary cause (or despite treatment)
    2. White Blood Cell Count >20,000/mm3
    3. Associated Anemia, Thrombocytopenia or Thrombocytosis
    4. Hepatomegaly, Splenomegaly or Lymphadenopathy
    5. Unexplained constitutional symptoms (e.g. fever, Fatigue or weight loss)
  4. Step 3: Based on Peripheral Smear interpretation
    1. Findings suggestive of benign cause
      1. Increased normal appearing Neutrophils
        1. Evaluate for causes of Neutrophil predominance (see above)
      2. Increased normal appearing Lymphocytes
        1. Evaluate for causes of Lymphocyte predominance (see above)
      3. Atypical lymphocytes
        1. Consider EBV, CMV or HIV
    2. Findings suggestive of Leukemia
      1. Increased blast cells
        1. Possible Acute Leukemia
        2. Test preipheral blood or Bone Marrow for immunophenotyping
      2. Few blast cells and increased Basophils and Eosinophils
        1. Possible Chronic Myelogenous Leukemia
        2. Test peripheral blood or Bone Marrow for Philadelphia Chromosome testing
      3. Significant increase of normal appearing Lymphocytes (>50% of cells)
        1. Possible Chronic Lymphocytic Leukemia
        2. Test peripheral blood for clonal expansion of B Lymphocytes >5000/mm3

IX. Management

  1. Hematology-Oncology Referral
  2. Treatment complications
    1. Neutropenic Fever
    2. Tumor Lysis Syndrome
  3. Post-cancer management
    1. See specific Leukemia
    2. See Cancer Survivor Care

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