Chronic Lymphocytic Leukemia

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Chronic lymphocytic leukemia/small lymphocytic lymphoma is most often discovered coincidentally during a routine checkup or blood test performed for an unrelated complaint or condition. For other people, CLL/SLL may be diagnosed after symptoms develop. No matter what triggers the evaluation for leukemia, it begins with the medical history and physical exam.

During the medical history, the doctor will ask you questions about your health to find clues as to whether you might have CLL/SLL and how the disease could be affecting you. Your doctor will ask how severe your symptoms are, how often you have them, and how long they last. The risk for CLL/SLL can be inherited, so be prepared to answer questions regarding your history of disease and that of your immediate family.

During the physical exam, the doctor will check for swelling of the lymph nodes, spleen, and liver and listen to your heart and lungs. Your blood pressure and pulse will be measured. Your doctor will look for physical signs of infection and evaluate your skin color and condition. Your physician will also look for signs of any other cancers, especially on your skin.

Based upon the results of the history and physical exam, your doctor may order additional testing. Despite the sophistication of many testing procedures and the valuable information they can provide, tests alone do not provide a diagnosis. Your doctor is ultimately responsible for interpreting test results, so it's vital that he or she have a good grasp of what each test can and cannot reveal about your condition. Before moving forward with a diagnostic test, especially an invasive test like bone marrow biopsy, review with your doctor how the results will add to his or her understanding of your condition.

This section includes information on:

  • Blood sampling
  • Bone marrow examination
  • Laboratory tests
  • Imaging
  • Blood sampling

    Blood testing is routinely performed as part of an evaluation for leukemia as well as during treatment and follow-up care. A definitive diagnosis of CLL/SLL can be made from a blood specimen.

    Preparation for a blood test may require abstaining from food or drink for a period of hours beforehand. During the procedure, samples of blood are drawn from a vein, usually from the inside of the elbow or the back of the hand, using a thin, hollow needle.

    Bone marrow examination

    A bone marrow examination is not required to diagnose CLL/SLL but can provide important information at different times in the management of the disease. Analysis of bone marrow is used to plan treatment and evaluate the effectiveness of treatment.

    During a bone marrow examination, samples of the liquid and solid portions of the bone marrow are collected. A bone marrow biopsy refers to a sample of the solid bone marrow material; a bone marrow aspiration is a sample of the liquid portion of the marrow.

    Biopsy and aspiration of bone marrow are invasive and painful procedures that require the use of analgesia and sedation to minimize the discomfort. These procedures are usually performed in a medical center on an outpatient basis, using conscious sedation. Given through an IV, conscious sedation uses medications to minimize pain and make it less likely that you'll remember the procedures, but it also adds time to the procedures, compared with local anesthesia, which reduces the pain of the procedures while involving less preparation and recovery time and fewer potential complications.

    The bone marrow aspiration begins with the patient lying down on his or her side. Bone marrow samples are usually collected from the back of the hipbone at the top of the buttocks. After the area is disinfected, the doctor inserts a thick hollow needle, about one third the width of a pencil, equipped with a handle on one end to help guide the needle into the bone. The needle is moved through the bone with a twisting motion. This procedure may cause a deep aching pain because the anesthetics are not able to numb the interior of the bones. A syringe is used to extract about 1 teaspoon of liquid bone marrow. If you are awake, the suction may cause a sharp stinging or pulling sensation that stops as soon as the sample is collected.

    A bone marrow aspiration is usually followed by a bone marrow core biopsy in the same area. After the aspiration needle, the doctor carefully inserts a slightly larger needle farther into the bone marrow to collect a sample of the bone core. The core biopsy is a small solid piece of bone and marrow (about 1/16 inch in diameter and ½ inch long) that is removed. After the biopsy needle is removed, the core biopsy is extracted from the needle for examination under a microscope. The aspiration and biopsy usually take only about 30 minutes, but the entire examination may last two hours depending upon the type of anesthetic you select.

    After the procedure, pressure will be held against the biopsy site for a few minutes, and a pressure dressing is applied to reduce bleeding. Recovering from local anesthesia usually requires only 15 to 30 minutes. After that, you can return to normal activities. If the procedure was done using IV sedation, you will need to stay at the health center until the sedative wears off, and you will not be able to drive home. It may take 24 hours to regain full use of your faculties—judgment, memory, and normal response time—after IV sedation.

    At home, the pressure bandage needs to stay on and dry for 24 hours following the procedure. It's not unusual to experience a small amount of bleeding over the first 24 hours or feel pain for a week or so after a bone marrow biopsy and aspiration.

    If any of the following conditions develop, get in touch with your healthcare provider:

    • Excessive bleeding that soaks the bandage or doesn't stop with direct pressure

    • A fever above 100.4 degrees Fahrenheit

    • Unrelenting pain

    • Swelling, increasing redness, or drainage at the biopsy site

    Complications of a bone marrow biopsy and aspiration are rare and usually mild. They include excessive bleeding, infection, prolonged pain, or complications related to IV sedation such as allergic reaction, nausea, or irregular heart rhythms.

    Laboratory tests

    Blood or bone marrow samples can be analyzed in a number of ways. These may be used as part of diagnosis, to help your doctor plan your treatment, to check how well a treatment is going, or as part of your follow-up care after treatment.

    Complete blood count. This is an evaluation of the overall health of your blood. The results of the CBC are not used to diagnose leukemia alone but can help the doctor decide if you need additional diagnostic testing. If you are already being treated for CLL/SLL, the CBC can help evaluate the effectiveness of treatment.

    The CBC evaluates the characteristics and amounts of the different blood cells and can indicate the presence of abnormal cells. The fraction of blood consisting of red blood cells is reported as the hematocrit. The mean corpuscular volume is a measure of the size of the red blood cells. The number of platelets and the different types of white blood cells (lymphocytes, monocytes, neutrophils, basophils, and eosinophils) are included in the results. A lymphocyte count of more than 5 billion per liter of blood is suggestive of CLL, but confirmation of the disease requires more specialized tests discussed below.

    General blood chemistry. This is the analysis of the fluid portion of the blood that remains after the blood cells have been removed. Usually 20 or more chemical tests including electrolyte levels are included in this analysis. Coagulation studies, which determine how long it takes for blood to clot, may also be performed.

    Analysis of general blood chemistry helps your doctor understand how well your vital organs, including the liver and kidneys, are working and can rule out other diseases that could be causing your symptoms. If you are being treated for CLL/SLL, the general chemistry test may be used to look for evidence of liver or kidney damage caused by the treatment or complications of the disease. These tests also help determine if treatment is needed to correct abnormally low or high levels of certain minerals in the blood resulting from CLL/SLL or its treatment.A blood protein known as immunoglobulin may be evaluated to verify that there are enough antibodies to fight infections. This may be particularly important if the patient has had many infections recently. Elevated concentrations of another blood protein called beta-2-macroglobulin may indicate a more advanced CLL/SLL.

    Conventional microscopic evaluation. Blood and bone marrow samples can also be examined visually, through a microscope, to help diagnose chronic lymphocytic leukemia/small lymphocytic lymphoma. Microscopic examination is also performed during treatment or as part of follow-up care after treatment to make sure the leukemia hasn't returned.

    A drop of blood is spread into a thin film on a glass slide and allowed to dry. Dyes are then applied to color the different types of blood so that they are easy to identify and evaluate under a microscope.

    Fluorescent in situ hybridization. This is a cytogenetic test that uses special fluorescent proteins to detect chromosome abnormalities in samples of blood or bone marrow. FISH is used to look for abnormalities that are linked to chronic lymphocytic leukemia/small lymphocytic lymphoma. Identifying the specific abnormalities helps your doctor predict how your disease will progress and determine the most effective course of treatment.

    Flow cytometry. This is the blood test most often used to diagnose chronic lymphocytic leukemia/small lymphocytic lymphoma. In addition, it can detect small amounts of residual disease in patients after treatment. Flow cytometry also measures the amount of the proteins ZAP-70 and CD38 in CLL cells. The presence of these proteins is used to determine how rapidly the disease is likely to progress.

    Samples of blood are treated with light-sensitive chemicals and then passed in front of a laser beam. The amount of light given off by the sample is interpreted by a computer to identify chromosomal abnormalities and the presence of cellular proteins.

    Immunophenotyping. Samples of tissue are analyzed using immunophenotyping to look for the presence of abnormal cells associated with chronic lymphocytic leukemia/small lymphocytic lymphoma. This test is usually performed on samples of bone marrow or lymph nodes. The prevalence of CLL in the bone marrow is used by your doctor to help determine the timing for treatment.

    Tissue samples are treated with fluorescent chemicals that attach themselves to the abnormal cells. A conventional microscope is used to visually inspect the samples and count the abnormal cells.

    Polymerase chain reaction. This is a very specialized and sensitive molecular test. PCR is performed on either blood or bone marrow samples to identify leukemia cells based on the cells' genetic abnormalities. This test can find one tumor cell among a hundred thousand normal cells. PCR is primarily used to monitor a patient's health after treatment.


    Medical imaging tests are used to assess the condition of the internal organs. These tests may be performed as part of the diagnosis to rule out other conditions that may be causing symptoms, to look for possible signs of leukemia in your internal organ, to prepare for treatment, or as part of follow-up care. Common imaging tests that your doctor may order include a chest X-ray and computed tomography of the chest, abdomen, and pelvis.

    Chest X-ray. In a chest X-ray, electromagnetic energy creates images of the internal organs and tissues, including bones. A chest X-ray can show the size, shape, position, and condition of the lungs. Chest X-rays are often performed following treatment to evaluate the condition of the lungs.

    Getting a chest X-ray doesn't hurt. Before the test, you will need to remove all clothing and jewelry from the waist up. During the X-ray, you will most likely be asked to stand against the plate containing the X-ray film and roll your shoulders forward while holding your arms at your sides so they do not interfere with the picture. The radiologist or technician will ask you to take a deep breath and hold it as the X-ray picture is taken. Holding your breath fills your lungs with air and helps your heart and lungs show up more clearly on the film.

    Although a chest X-ray exposes you to a small amount of radiation, the benefits of the image greatly outweigh the slight increase in cancer risk posed by the radiation. However, women who have any chance of being pregnant at the time the X-ray is taken should tell their doctors, so that they can allow for special precautions to minimize the developing fetus's exposure to radiation.

    Computed tomography. In computed tomography, X-rays are collected from many different angles around the body and used to generate detailed cross-sectional images as well as three-dimensional images of the body's internal structures and organs. CT scans may be used in patients with CLL to measure the size of lymph nodes in the chest, abdomen and pelvis, spleen, and liver.

    The procedure is painless and requires the patient to lie as still as possible on a table that is guided into a machine that resembles an enormous doughnut. The machine, called a gantry, directs small doses of electromagnetic radiation toward the body from various angles. Because different tissues of the body absorb varying amounts of radiation, a computer can analyze the radiation transmitted through the body to reconstruct the images of the internal structures and organs.

    Chest and abdominal CT scans involve exposure to a significantly higher dose of radiation than a normal X-ray. For most patients, the benefits outweigh the risks associated with this level of radiation. However, pregnant women may prefer to postpone getting a CT scan until after they've delivered their baby or choose alternative testing procedures. Individuals with pacemakers or internal cardioverter defibrillators who have been advised to avoid magnetic resonance imaging can safely have a CT scan.

    Last reviewed on 07/01/2008

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