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How We Diagnose Chronic Lymphocytic Leukemia

  • Matthew Davids, MD, MMSc, associate director of the Center for Chronic Lymphocytic Leukemia, describes advances in treating newly-diagnosed and relapsed CLL.

  • At the Center for Chronic Lymphocytic Leukemia at Dana-Farber Brigham Cancer Center, the oncologists who lead your treatment team work closely with hematopathologists to diagnose your condition and guide your treatment.

    We have unique expertise in interpreting molecular and genomic tests and translating that data into an action plan. For every patient, we conduct a personalized CLL risk assessment that will give you detailed, specific information about your disease as soon as you're diagnosed — and help your care team build a customized treatment plan.

    The diagnostic evaluation and staging for CLL include the tests described below:

    Complete Blood Count (CBC) with Differential

    This is a procedure in which a sample of blood is drawn and checked for the following:

    • The number of red blood cells and platelets
    • The number and type of white blood cells
    • The amount of hemoglobin (the protein that carries oxygen) in the red blood cells
    • The portion of the blood sample made up of red blood cells

    Flow Cytometry

    This is a laboratory test that measures the number of cells in a sample; the percentage of live cells in a sample; and certain characteristics of cells, such as size, shape, and the presence of tumor markers on the cell surface. The cells are stained with a light-sensitive dye, placed in a fluid, and passed in a stream before a laser or other type of light. The measurements are based on how the light-sensitive dye reacts to the light.

    Blood Chemistry Studies

    This is procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it.

    We take findings from all of the above tests and integrate them to make an accurate diagnosis of the cancer type.

    Prognostic Tests

    Following a diagnosis, several prognostic tests may be used to determine the course of your disease and treatment.

    View a video of Jennifer Brown, MD, PhD, discussing how genomic sequencing plays a role in determining prognosis and treatment for patients with CLL

    FISH (Fluorescence In Situ Hybridization)

    This is a laboratory technique used to look at genes or chromosomes in cells and tissues. Pieces of DNA that contain a fluorescent dye are made in the laboratory and added to cells or tissues on a glass slide. When these pieces of DNA bind to specific genes or areas of chromosomes on the slide, they light up when viewed under a microscope with a special light.

    Our Rapid Heme Panel tests blood cancer specimens for mutations to quickly detect genes that predict prognosis and response to therapies.

    • It uses next-generation sequencing to identify single mutations or DNA alterations in 95 genes that are frequently mutated in blood cancers, making it the most comprehensive, swiftest blood cancer mutation test available today.
    • Results help identify the most appropriate clinical trial or treatment approach.

    IGHV Mutation Analysis

    This analysis can help identify whether your CLL is more likely to be indolent (slow-growing) or aggressive based on the presence or absence of a mutated Immunoglobulin Heavy Chain Variable (IGHV) gene. Patients with mutated IGHV are predicted to have a more slow-growing form of CLL and are less likely to require treatment soon after diagnosis.


    Staging is the process used to find out how far the cancer has spread. It is important to know the stage of the disease in order to plan the best treatment. We follow the Rai staging system, which uses physical exam (not CT scans) to evaluate lymph nodes, spleen, and liver.

    • Stage 0: Lymphocytosis and no enlargement of the lymph nodes, spleen, or liver, and with near normal red blood cell and platelet counts.
    • Stage I: Lymphocytosis plus enlarged lymph nodes. The spleen and liver are not enlarged and the red blood cell and platelet counts are near normal.
    • Stage II: Lymphocytosis plus an enlarged spleen (and possibly an enlarged liver), with or without enlarged lymph nodes. The red blood cell and platelet counts are near normal.
    • Stage III: Lymphocytosis plus anemia (too few red blood cells), with or without enlarged lymph nodes, spleen, or liver. Platelet counts are near normal.
    • Stage IV: Lymphocytosis plus thrombocytopenia (too few blood platelets), with or without anemia, enlarged lymph nodes, spleen, or liver.

    Most patients who are diagnosed before stage III-IV do not need immediate treatment and are closely followed through watchful waiting.

    Most patients newly diagnosed with CLL will not require imaging tests. If your physician recommends one, it will most likely be a CT scan (CAT scan). A CT scan is a procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an X-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.

    PET/CT scans are used occasionally for CLL. The procedure combines the pictures from a positron emission tomography (PET) scan and a computed tomography (CT) scan. The pictures from both scans are combined to create a more detailed picture than either test would produce by itself. The procedure is done to find tumor cells; in the case of CLL, we often use this test to look for disease evolution to a more aggressive type.