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Chronic Lymphocytic Leukemia (CLL)

by Michael E. Rytting, MD

Chronic lymphocytic leukemia is a disease in which mature-appearing lymphocytes become cancerous and gradually replace normal cells in lymph nodes.

  • People may have no symptoms, or they may have general symptoms such as tiredness.

  • People may also have enlarged lymph nodes and a sense of abdominal fullness.

  • Blood tests and examination of a bone marrow sample are needed for diagnosis.

  • Treatment includes chemotherapy drugs, monoclonal antibodies, and sometimes radiation therapy.

More than three fourths of the people who have chronic lymphocytic leukemia (CLL) are older than 60, and the disease does not occur in children. This type of leukemia affects men 2 to 3 times more often than women. CLL is the most common type of leukemia in North America and Europe. It is rare in Japan and Southeast Asia, which indicates that genetics plays some role in its development.

The number of cancerous, mature lymphocytes increases first in the blood, bone marrow, and lymph nodes. They then spread to the liver and spleen, both of which begin to enlarge. In the bone marrow, cancerous lymphocytes may crowd out normal cells, resulting in a decreased number of red blood cells and a decreased number of normal white blood cells and platelets in the blood. The level of antibodies, proteins that help fight infections, also decreases. The immune system, which ordinarily defends the body against foreign organisms and substances, sometimes becomes misguided, reacting to and destroying normal body tissues. This misguided immune activity can result in the destruction of red blood cells and platelets.

In the great majority of cases, CLL is a disorder of B lymphocytes (B cells—see see Biology of the Immune System:B cells). There are other types of CLL other than B-cell CLL. Hairy cell leukemia, a slow-growing uncommon type of B-cell leukemia, produces a large number of abnormal white blood cells with distinctive hairlike projections that are visible under a microscope. T-cell CLL (leukemia of T lymphocytes) is much less common than B-cell CLL.

Did You Know...

  • Chronic lymphocytic leukemia does not occur in children.

Symptoms and Diagnosis

In early stages of CLL, most people have no symptoms, and the disease is diagnosed only because of an increased white blood cell count. Later symptoms may include enlarged lymph nodes, fatigue, loss of appetite, weight loss, shortness of breath when exercising, and a sense of abdominal fullness resulting from an enlarged spleen.

As CLL progresses, people may appear pale and bruise easily. Bacterial, viral, and fungal infections generally do not occur until late in the course of the disease.

Sometimes CLL is discovered accidentally when blood counts ordered for some other reason show an increased number of lymphocytes. A bone marrow evaluation is frequently done to confirm the diagnosis and to determine how far CLL has progressed (staging). Specialized tests to characterize the abnormal lymphocytes can be done on the cells in the blood. Blood tests also may show that the numbers of red blood cells, platelets, and antibodies are low.


Usually CLL progress slowly. Doctors determine how far the disease has progressed to predict the survival time. Staging is based on factors such as the number of lymphocytes in the blood and bone marrow, size of the spleen and liver, presence or absence of anemia, and platelet count.

People who have CLL often survive 10 to 20 years or longer after the diagnosis is made and usually do not need treatment in the early stages. People who are anemic or who have a low number of platelets need more immediate treatment and have a less favorable prognosis. Usually, death occurs because the bone marrow can no longer produce a sufficient number of normal cells to carry oxygen, fight infections, and prevent bleeding. The prognosis for people who have T-cell CLL is usually worse.

For reasons probably related to changes in the immune system, people who have CLL are more likely to develop other cancers, such as skin or lung cancers. CLL can also transform into a more aggressive type of cancer of the lymphatic system (lymphoma).


Because CLL progresses slowly, many people do not need treatment for years—until the number of lymphocytes begins to increase and cause symptoms, the lymph nodes begin to enlarge, or the number of red blood cells or platelets decreases.

Drugs, including corticosteroids, chemotherapy drugs, and monoclonal antibodies, help relieve symptoms and shrink enlarged lymph nodes and spleen but do not cure the disease. Treatment can control CLL for many years and can often be used again with success when the leukemia regrows.

For B-cell CLL, initial drug treatment includes drugs such as fludarabine and cytoxan, which kill cancer cells by interacting with DNA. Currently, chemotherapy and a monoclonal antibody called rituximab are used to treat CLL. This combination therapy usually is successful in inducing remission. Eventually, most CLL becomes resistant to these drugs. Treatments with other drugs or other monoclonal antibodies (such as alemtuzumab) are then considered. For hairy cell leukemia, 2-chlorodeoxyadenosine and deoxycoformycin are highly effective and can control the disease.

Anemia due to a decreased number of red blood cells is treated with blood transfusions and occasionally with injections of erythropoietin or darbepoietin (drugs that stimulate red blood cell formation). Low platelet counts are treated with platelet transfusions, and infections are treated with antibiotics. Radiation therapy is used to shrink enlarged lymph nodes or an enlarged liver or spleen if the enlargement is causing discomfort and chemotherapy is ineffective.

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