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Chronic Lymphocytic Leukemia

(CLL)

By Michael E. Rytting, MD, Department of Leukemia, University of Texas MD Anderson Cancer Center;Department of Pediatrics, University of Texas MD Anderson Cancer

Chronic lymphocytic leukemia is usually a slowly progressing disease in which mature-appearing lymphocytes become cancerous and gradually replace normal cells in lymph nodes (see Overview of Leukemia).

  • 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-appearing lymphocytes increases first in the blood, bone marrow, and lymph nodes. Cancerous lymphocytes 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). There are other types of CLL other than B-cell CLL, including

  • Hairy cell leukemia

  • T-cell leukemia

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.

Sezary syndrome is sometimes regarded as a type of CLL. It occurs when the cells of mycosis fungoides (a T-cell lymphoma of the skin) spread into the blood.

Did You Know...

  • Chronic lymphocytic leukemia does not occur in children.

Symptoms

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

  • 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.

Diagnosis

  • Blood tests

  • Bone marrow examination

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.

Prognosis

Usually CLL progress slowly. Doctors determine how far the disease has progressed (staging) to predict the survival time. Staging is based on several factors, including the

  • Number of lymphocytes in the blood

  • Number of lymphocytes in the bone marrow

  • Size of the spleen

  • Size of the liver

  • Number of red blood cells in the blood

  • Number of platelets in the blood

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 have a low number of red blood cells (anemia) or 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).

Treatment

  • Chemotherapy

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.

Drug treatment

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 controlling CLL (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.

Ibrutinib is a new drug that has induced lasting remissions in some people with CLL that does not respond to other treatment (refractory) or relapsed CLL. Doctors are studying ways to use this drug as part of chemotherapy for CLL.

Treatment of CLL symptoms

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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