I. Definition, pathophysiology, and epidemiology

  1. A malignant neoplasm involving clonal expansion of relatively mature lymphocytes
  2. Considered a  type of non-Hodgkin lymphoma
  3. Non-functioning lymphocytes accumulate in peripheral blood, bone marrow, spleen, liver and/or lymph nodes
  4. 95% B-cell, 5% T-cell
  5. Growth and maturation of normal B-cells are inhibited, so often get impairment of humoral immunity
    1. 25% have hypogammaglobulinemia; 10% have hypergammaglobulinemia
    2. 5% have a monoclonal gammopathy (usually IgM), but usually don't get viscosity problems
  6. Median age at diaagnosis 70yo; rare at < 40yo; slight male predominance

II. Clinical presentation: highly varied!

  1. 70% are asymptomatic at time of diagnosis, which is usually incidental based on labs or Px
    1. However, can present with typical "B symptoms" of lymphoma (weakness, night sweats, weight loss and fever)
  2. High lymphocyte count on CBC
  3. Nontender adenopathy (may be intermittent) and splenomegaly (from infiltration with lymphocytes)
  4. Pancytopenia
  1. Recurrent infections when marrow replacement occurs
  2. Bleeding when marrow replacement produces thrombocytopenia
  1. Usually no constitutional symptoms until late, when can get night sweats, weight loss, and massive lymphadenopathy
  2. Blast crises are very rare
  3. Autoimmune hemolytic anemia and ITP can occur
  4. Median survival is 4-10y depending on stage (asymptomatic disease is associated with longer survival)
  5. Median survival after initiate of treatment is around 5 years
  6. "Smoldering" CLL refers ( early-stage disease with minimal lymphocytosis and lymph node involvement)-survival is similar to that of age- and sex-matched controls.

III. Diagnosis

  1. Peripheral blood smear showing
    1. Lymphocytosis, sometimes as high as 600k/uL
    2. In 10-20% of cases can see neutropenia, normochromic normocytic anemia, thrombocytopenia, and evidence of hemolytic anemia 
  2. Flow cytometry (to determine the immune phenotype of the lymphoid cells)
  3. One common diagnostic criteria set is ≥5,000 B-lymphocytes/ÁL on peripheral smear and B-lymphocyte clonality confirmed by flow cytometry
    1. If the latter but not the former is present, sometimes referred to as small lymphocytic lymphoma (SLL). Most SLL patients present with lymphadenopathy
  4. Excess lymphocytes in marrow
  5. Lymp node biopsy revealing "diffuse well-differentiated lymphoma"
  6. SPEP (see above re: globulinemias)
  7. Bone marrow biopsy may be performed to rule out acute leukemias

IV. Staging: Two systems, "Rai" (most common in U.S.)and "Binet"-See: are based on presence and/or degree of:

  1. Lymphocytosis
  2. Lymphadenopathy
  3. Hepatosplenomegaly
  4. Anemia
  5. Thrombocytopenia

V. Treatment

  1. Observation alone is common until patient becomes symptomatic with evidence of disease progression, e.g.:
    1. "B symptoms" (fever, fatigue, night sweats x > 1 month, weight loss >10% in 6 months)
    2. Symptomatic or worsening anemia or thrombocytopenia
    3. Autoimmune hemolytic anemia or thrombocytopenia not responsive to corticosteroids
    4. Lymphadenopathy or hepatosplenomegaly that is massive, progressive or painful
    5. Progressive lymphocytosis (doubling time <6 months)
    6. Recurrent infections
  2. Medical treatment: fludarabine, rituximab, cyclophosphamide, alemtuzumab, benadmustine in various combinations
  3. IVIG may decrease infections in hypogammaglobulinemic patients, but no clear increase in survival
  4. Radiation may be uased for palliation of large, painful lymph nodes
  5. Splenectomy occasionally done is painful splenomegaly with severe anemia or clinically significant thrombocytopenia; probably doesn't increase survival
  6. Yearly influenza vaccine and Q5y pneumococcal vaccines are recommended; live vaccines should be avoided unless pt is in remission and has had no treatment for last 3mos

(Sources include Sci. Am. Medicine, 10/94; Core Content Review of Family Medicine, 2012)