Chronic lymphocytic leukemia




Chronic lymphocytic leukemia (CLL) is a cancer of the lymphocytes that begins in the stem cells of the bone marrow and then invades the blood. The term "chronic" in chronic lymphocytic leukemia comes from the fact that it typically progresses more slowly than other types of leukemia. The term "lymphocytic" refer to the cells affected by the disease — a group of white blood cells called lymphocytes, which help your body fight infection. Overtime, CLL may also spread to the lymph nodes and other organs including the liver, spleen and lungs. It occurs when the stem cells that make lymphocytes become out of control and produce increasing amounts of abnormal lymphocytes (also called leukemic cells). Eventually, these abnormal cells replace normal lymphocytes and can crowd out other types of normal blood cells, leading to the features of the condition. CLL most commonly affects adults over age 45. There are treatments to help control the disease.


Chronic lymphocytic leukemia is the most common form of leukemia in adults and is rarely diagnosed in people under age 45. Many people affected by CLL have no symptoms at the time of diagnosis. In these cases, the condition is often identified incidentally (by chance) during a routine blood test. Less commonly, CLL may present with enlarged lymph nodes without a high white blood cell count or no evidence of the disease in the blood. This is referred to as small lymphocytic lymphoma. In some individuals, the disease comes to light only after the neoplastic cells overwhelm the bone marrow resulting in anemiaproducing tiredness or weakness. The symptoms of CLL usually develop slowly although the condition can progress more quickly in rare cases.

The signs and symptoms of CLL vary, but may include:

  • Enlarged lymph nodes, liver and/or spleen
  • Night sweats
  • Fever
  • Fatigue
  • Loss of appetite
  • Weight loss
  • Frequent infections
  • Abnormal bruising
  • Pain in the upper left portion of the abdomen, which may be caused by an enlarged spleen


The exact underlying cause of chronic lymphocytic leukemia (CLL) is unknown. Although approximately 5% of people affected by CLL have other family members with the condition, no genetic cause has been identified.

Doctors know that something happens to cause a genetic mutation in the DNA of blood-producing cells. This mutation causes the blood cells to produce abnormal, ineffective lymphocytes — a type of white blood cell that helps your body fight infection. Beyond being ineffective, these abnormal lymphocytes continue to live and multiply, when normal lymphocytes would die. The abnormal lymphocytes accumulate in the blood and certain organs, where they cause complications. They may crowd healthy cells out of the bone marrow and interfere with normal blood cell production.

Factors that increase the risk for CLL include:

  • Being over age 45
  • Being male
  • Being white
  • Having other family members with CLL or other cancers of the lymph system
  • Being exposed to Agent Orange (a pesticide used to kill unwanted plants) during the Vietnam War 

It is important to note that although these factors increase the risk for CLL, it does not mean that CLL will develop; not having one of these risk factor does not mean that CLL will not develop.

Chronic lymphocytic leukemia may cause complications such as:

  • Frequent infections. People with chronic lymphocytic leukemia may experience frequent infections. In most cases, these infections are common infections of the upper and lower respiratory tract. But sometimes more-serious infections can develop.
  • A switch to a more aggressive form of cancer. A small number of people with chronic lymphocytic leukemia may develop a more 
  • aggressive form of cancer called diffuse large B-cell lymphoma. Doctors sometimes refer to this switch as Richter's syndrome


There is no way to prevent CLL. You can't catch CLL from someone else. CLL has generally not been associated with any environmental or external factors. However, the Institute of Medicine of the National Academy of Sciences issued a report, which concluded that there was "sufficient evidence of an association" between herbicides used in Vietnam and CLL.


Chronic lymphocytic leukemia is often discovered incidentally (by chance) when abnormally high levels of white blood cells are observed during a routine blood test. A diagnosis of CLL is usually confirmed by a bone marrow biopsy, a lymph node biopsy and/or blood tests (i.e. complete blood count, flow cytometry). A complete blood count measures the number of each type of blood cell, while flow cytometry closely examines blood cells to determine if they are cancerous.

Other specialized laboratory testing may be ordered to gain information regarding the course of CLL. These tests may help predict the response to treatment and/or the likelihood of relapse.

Tests and procedures used to diagnose chronic lymphocytic leukemia include blood tests designed to:

  • Count the number of cells in a blood sample. A complete blood count may be used to count the number of lymphocytes in a blood sample. A high number of B cells, one type of lymphocyte, may indicate chronic lymphocytic leukemia.
  • Determine the type of lymphocytes involved. A test called flow cytometry or immunophenotyping helps determine whether an increased number of lymphocytes is due to chronic lymphocytic leukemia, a different blood disorder or your body's reaction to another process, such as infection. If chronic lymphocytic leukemia is present, flow cytometry may also help analyze the leukemia cells for characteristics that help predict how aggressive the cells are.
  • Analyze lymphocytes for genetic abnormalities. A test called fluorescence in situ hybridization (FISH) examines the chromosomes inside the abnormal lymphocytes to look for abnormalities. Doctors sometimes use this information to determine your prognosis and help choose a treatment.

Other tests:
In some cases, your doctor may order additional tests and procedures to aid in diagnosis, such as:

  • Tests of your leukemia cells that look for characteristics that could affect your prognosis
  • Bone marrow biopsy and aspiration
  • Imaging tests, such as computerized tomography (CT)


Once a diagnosis is confirmed, your doctor determines the extent (stage) of your chronic lymphocytic leukemia. Two different staging systems are used. Each assigns a stage — early, intermediate or advanced — that indicates the progression of a person's chronic lymphocytic leukemia. These levels are used to determine treatment options.

In general, people with early-stage disease don't require immediate treatment. Those with intermediate-stage disease and advanced-stage disease may be given the option to begin treatment right away.


The long-term outlook (prognosis) for people with chronic lymphocytic leukemia varies based on many factors, including the stage of the condition; whether abnormal lymphocytes have spread throughout the bone marrow and to other parts of the body; the affected person's response to treatment; and the affected person's general health. Approximately half of people diagnosed in the early stages of CLL live more than 12 years. Later stages of CLL are often associated with significant health problems and disability, both from the condition and from complications of treatment.


The best treatment for chronic lymphocytic leukemia (CLL) depends on many factors, including the stage of the condition, the age of the affected person, the blood cell counts, whether the CLL has recurred, and the signs and symptoms present in each person. For example, people affected by an early stage of CLL who have not yet developed any signs or symptoms of the condition may simply be closely monitored by their physician without any treatment (watchful waiting).

If your doctor determines your chronic lymphocytic leukemia is progressing or is in the intermediate or advanced stages, your treatment options may include:

  • Chemotherapy. Chemotherapy is a drug treatment that kills cancer cells. Chemotherapy treatments can be administered through a vein or taken in pill form. Depending on your situation, your doctor may use a single chemotherapy drug or you may receive a combination of drugs.
  • Targeted drug therapy. Targeted drugs are designed to take advantage of the specific vulnerabilities of your cancer cells. Targeted therapy drugs used in treating chronic lymphocytic leukemia include alemtuzumab (Campath), ibrutinib (Imbruvica), idelalisib (Zydelig), lenalidomide (Revlimid), obinutuzumab (Gazyva), ofatumumab (Arzerra) and rituximab (Rituxan), venetoclax (Venclexta).


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