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February 20, 2019

Diagnosis

A CLL diagnosis comes with new challenges, from understanding signs and symptoms and what the different stages mean.
PUBLISHED February 20, 2019
Signs and Symptoms
Most people with chronic lymphocytic leukemia (CLL) do not have symptoms when they receive their diagnosis. Typically, the first sign of the disease occurs when a blood test ordered for an unrelated health condition or a routine checkup reveals a high number of white blood cells called lymphocytes. As the disease progresses, symptoms may include:
  • Weakness.
  • Feeling tired.
  • Weight loss.
  • Chills.
  • Fever.
  • Night sweats.
  • Changes in appetite and sleep.
  • Swollen lymph nodes (on areas such as the armpits, front and sides of the neck, and above the collarbone.)
  • Enlarged spleen or liver.
  • Increased risk of infections.
  • Easy bleeding or bruising.
Determining a Diagnosis
The doctor will start by taking a complete medical history and doing a physical exam to look for possible signs of leukemia. These tests are also available to diagnose and classify leukemia.
  • Blood tests: A complete blood count measures the number of red blood cells, white blood cells and platelets, and a differential test measures the percentage of each type of white blood cell. People with CLL have high levels of lymphocytes, and doctors can use a microscope to look for abnormal lymphocytes. Another type of test, flow cytometry, uses an instrument to look for markers on cells that indicate if the lymphocytes in a blood sample contain CLL cells. A diagnosis of CLL requires the presence of 5,000 abnormal B cells per microliter of blood. This test can also screen for proteins called zeta-chain-associated protein (ZAP-70) and cluster of differentiation 38 (CD38) on CLL cells. Studies suggest that people who have lower levels of CLL with these proteins have a better prognosis. Chemistry tests are designed to assess liver, kidney and other organ function.
  • Bone marrow tests: Although blood tests are often sufficient to diagnose CLL, testing the bone marrow indicates how advanced the disease is. A bone marrow aspiration or biopsy is often done before starting treatment or to evaluate the effectiveness of therapy. Doctors look at the white blood cells’ size, shape and other traits under a microscope. 
  • Gene tests: With cytogenetics, bone marrow or cells from the blood viewed under a microscope can reveal if part of a chromosome has been deleted, added or moved. This information helps determine a patient’s prognosis. Fluorescent in situ hybridization uses fluorescent dyes to identify certain genes or chromosome changes.
Staging
Doctors use a staging system to describe a patient’s cancer — there are two systems for CLL.
The Rai system, which classifies cancer according to risk, is used most often in the United States.
  • Low risk (stage 0): abnormal increase in number of lymphocytes in the blood and marrow.
  • Intermediate risk (stages 1 and 2): abnormal increase in number of lymphocytes in the blood and marrow and enlarged lymph nodes or enlarged spleen/liver.
  • High risk (stages 3 and 4): abnormal increase in the number of lymphocytes in the blood and marrow and anemia (low red blood cell count) or thrombocytopenia (low platelets).
The Binet staging system is more common in Europe.
  • Stage A: no anemia or thrombocytopenia; fewer than three areas of enlarged lymphoid tissue (located in the spleen, liver and lymph nodes in the neck, groin and underarm).
  • Stage B: no anemia or thrombocytopenia; three or more areas of enlarged lymphoid tissue.
  • Stage C: anemia and/or thrombocytopenia present; any number of areas of enlarged lymphoid tissue.

In addition to staging, doctors will use other factors to determine the prognosis. Favorable factors include a low proportion of CLL cells with ZAP-70 or CD38, deletion of part of chromosome 13, IGHV mutational status and a non-diffuse pattern of bone marrow involvement. Factors linked to a shorter survival time include advanced age, deletions of parts of chromosomes 17 or 11, TP53 mutations or a high proportion of cells with ZAP-70 or CD38, and a diffuse pattern of bone marrow involvement.
 
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