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For further information, see CMDT Part 13-30: Chronic Lymphocytic Leukemia

Key Features

Essentials of Diagnosis

  • Most patients are asymptomatic at presentation

  • B-cell lymphocytosis with CD19 expression > 5000/mcL

  • Mature morphologic appearance of lymphocytes

  • Coexpression of CD19, CD5

General Considerations

  • A clonal malignancy of B lymphocytes

  • The course is usually indolent, with slowly progressive accumulation of long-lived small lymphocytes that are immunoincompetent

  • Results in immunosuppression, bone marrow failure, and organ infiltration with lymphocytes

  • Immunodeficiency also related to inadequate antibody production by abnormal B cells

  • In severe disease, may cause damage by direct tissue infiltration

  • Prognostically useful staging system (Rai system)

    • Stage 0, lymphocytosis only

    • Stage I, lymphocytosis plus lymphadenopathy

    • Stage II, organomegaly (spleen, liver)

    • Stage III, anemia

    • Stage IV, thrombocytopenia

Demographics

  • Chronic lymphocytic leukemia (CLL) occurs mainly in older patients

    • 90% of cases occur in persons over age 50

    • Median age at presentation is 70

Clinical Findings

Symptoms and Signs

  • Incidentally discovered lymphocytosis in many patients

  • Fatigue

  • Diffuse lymphadenopathy in 80%

  • Hepatomegaly or splenomegaly in 50%

Differential Diagnosis

  • Atypical lymphocytosis due to bacterial or viral infection or pertussis

  • Lymphoma in its leukemic stage, especially mantle cell lymphoma

  • Hairy cell leukemia

  • Waldenström macroglobulinemia

  • Monoclonal B-cell lymphocytosis (MBL) characterized by < 5000/mcL B-cells is considered a precursor to B-CLL

Diagnosis

Laboratory Tests

  • White blood cell count is usually > 20,000/mcL (20 × 109/L) and may be markedly elevated to several hundred thousand

  • Differential: usually 75–98% of circulating cells are lymphocytes

  • Hematocrit and platelet count usually normal at presentation

  • On peripheral smear, lymphocytes are usually morphologically indistinguishable from normal small lymphocytes

  • Larger and more immature cells are found in prolymphocytic leukemia (PLL)

  • CLL is diagnosed by coexpression of B-lymphocyte lineage marker CD19 with T-lymphocyte marker CD5

  • CLL is distinguished from mantle cell lymphoma by

    • Expression of CD23

    • Low expression of surface immunoglobulin and CD20

    • Absence of overexpression of cyclin D1

  • High expression of CD38 or ZAP-70 is correlated with more aggressive course

  • Fluorescence in-situ hybridization (FISH) assesses genomic changes

  • Hypogammaglobulinemia is found in half of CLL patients, becomes more common with advanced disease

  • Serum protein electrophoresis: IgM paraprotein may be present

Diagnostic Procedures

  • Bone marrow is variably infiltrated with small lymphocytes

  • Lymph node biopsy shows same pathologic changes as in diffuse small lymphocyte lymphoma

Treatment

Medications

  • Most patients with early stage disease do not require treatment for months or years

  • Initial treatment options include

    • Ibrutinib or venetoclax in combination with anti-CD20 antibody therapy

    • Choice between these agents is based on toxicity as well as preference

  • Ibrutinib

    • A ...

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