Hematology and Oncology Book

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Chronic Lymphocytic Leukemia

Aka: Chronic Lymphocytic Leukemia, CLL
  1. Epidemiology
    1. Most common Leukemia in the United States
    2. Older patients
      1. Usually over age 50 years
      2. Age over 65 years old in 85% of new cases
    3. More common in men
    4. Rare in Asian patients
  2. Pathophysiology
    1. Neoplastic accumulation of mature Lymphocytes
      1. Involves Blood and Bone Marrow
      2. May infiltrate Spleen and lymph nodes
    2. Clonal B Lymphocyte mass involved in 95% of cases
    3. Chromosomal Abnormality: Trisomy 12
  3. Symptoms
    1. Asymptomatic in 50% of patients (found incidentally on CBC)
    2. Constitutional and generalized symptoms
      1. Weakness
      2. Fatigue
      3. Anorexia
      4. Pruritus
    3. Other presentations
      1. Frequent infections
  4. Signs
    1. Fever
    2. Hepatomegaly
    3. Splenomegaly
    4. Lymphadenopathy
  5. Labs
    1. Peripheral Smear
      1. Leukocytosis
      2. Morphologically normal small Leukocytes
        1. HemeoncCllBlood.jpg
    2. Complete Blood Count
      1. Leukocyte count 15,000 to 200,000 (80-90% mature)
        1. Clonal expansion of >5000 B Lymphocytes/mm3
      2. Decreased Platelet Count
      3. Hemoglobin or Hematocrit consistent with Anemia
  6. Differential Diagnosis
    1. B-Cell CLL
      1. Reactive Lymphocytosis
    2. T-Cell CLL
      1. Sezary Syndrome
      2. Adult T-Cell Leukemia
    3. General
      1. Prolymphocytic Leukemia
      2. Lymphosarcoma Cell Leukemia
      3. Hairy Cell Leukemia
      4. Waldenstrom's Macroglobulinemia
  7. Complications
    1. Pancytopenia
    2. Coombs-positive Hemolytic Anemia (20%)
    3. Hypogammaglobulinemia
    4. Opportunistic infection
    5. Richter's Syndrome (evolves into aggressive Lymphoma)
    6. Autoimmune Thrombocytopenia
  8. Imaging
    1. Chest XRay
      1. Enlarged mediastinal lymph nodes
  9. Management: Treatment
    1. Efficacy of treatment
      1. No regimen effective at eradicating CLL
      2. Goal is to reduce Leukemia cell mass and symptoms
    2. Alkylating Agents (pulsed q3-6 weeks or continuous)
      1. Indications
        1. Hemolytic Anemia and other cytopenia
        2. Disfiguring Lymphadenopathy
        3. Symptomatic organomegaly
        4. Marked systemic symptoms
      2. Agents
        1. Chlorambucil
        2. Cyclophosphamide
    3. Glucocorticoids
      1. Coombs-positive Hemolytic Anemia
      2. Immune Thrombocytopenia
      3. Pancytopenia
      4. "Packed Marrow" Syndrome
    4. Splenectomy indications
      1. Hypersplenism
      2. Refractory Hemolytic Anemia
      3. Thrombocytopenia
    5. Radiation Therapy indications
      1. Localized disease
      2. Palliative end-stage disease therapy (total-body)
    6. Immunoglobulin transfusion (not proven efficacious)
  10. Management: Surveillance for those under observation only (no treatment)
    1. Periodic constitutional symptom history
      1. Fatigue
      2. Weight loss
      3. Night Sweats
      4. Fever
    2. Periodic exam
      1. Hepatosplenomegaly
    3. Periodic Complete Blood Count (CBC)
      1. Hematology Consultation for Anemia or Thrombocytopenia
    4. Vaccination
      1. Influenza Vaccine yearly
      2. Pneumococcal Vaccine yearly
      3. Avoid Live Vaccines
      4. Routine cancer screening (appropriate for age and gender)
  11. Management: Surveillance for those who have been treated
    1. Cardiology Consultation for baseline examination
    2. Periodic Echocardiogram (rest and stress)
      1. Frequency depends on risks and Echocardiogram findings
  12. Course
    1. Indolent nature
    2. Often incidental finding on Complete Blood Count
  13. Staging
    1. Stage A: Lymphocytosis (<3 lymph node groups involved)
      1. Median survival: over 10 years
    2. Stage B: Lymphocytosis (>3 lymph node groups involved)
      1. Median survival: 5 years
    3. Stage C: Lymphocytosis with Anemia or Thrombocytopenia
      1. Median survival: 2 years
  14. Prognosis
    1. Age <50 years old: 94% five-year survival
    2. Age >50 years old: 83% five-year survival
  15. References
    1. Davis (2014) Am Fam Physician 89(9): 731-8 [PubMed]
    2. Yee (2006) Mayo Clin Proc 81(8): 1105-29 [PubMed]

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