Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a slowly progressing disease in which mature lymphocytes (a type of white blood cell) become cancerous and gradually replace normal cells in lymph nodes.

CLL is one of the four main types of leukemia and is the most common type in older people. The other three are acute lymphocytic leukemia, acute myelocytic leukemia, and chronic myelocytic leukemia. Most people who develop CLL are older than 60. CLL affects men 2 to 3 times more often than women.

Almost always, the cause of CLL is unknown. CLL begins with cancerous mature lymphocytes in the bone marrow, blood, and lymph nodes. The cancerous cells in the bone marrow crowd out normal cells, resulting in a decreased number of red blood cells, normal white blood cells (which help fight infection), and platelets (which are needed for blood clotting). Cancerous lymphocytes spread to the liver and spleen, both of which begin to enlarge. The levels of antibodies, proteins that help fight infections, also decrease. The immune system, which ordinarily defends the body against foreign organisms and substances, sometimes becomes impaired, reacting to and destroying normal body tissues, including red blood cells and platelets.

Treatment of CLL can relieve most symptoms for a very long time. However, for some people, complications develop that cause quality of life to deteriorate, and the potential benefit for further treatment becomes extremely limited.

Symptoms and Diagnosis

In early stages of CLL, most people have no symptoms. Gradually, people may see or feel bumps under the skin where lymph nodes have enlarged. Other later symptoms may include 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. Symptoms that may indicate infection, such as fever, tend to occur late in the course of the disease as the body's susceptibility to invading bacteria, viruses, and fungi increases.

Sometimes CLL is discovered accidentally when white blood cell counts done for some other reason show an increased number of lymphocytes. Specialized tests, performed on the cells in the blood to characterize the lymphocytes, usually confirm the diagnosis of CLL. Blood tests also may show that the person has a decreased number of red blood cells, platelets, and antibodies. A biopsy of the bone marrow is occasionally needed if the diagnosis remains uncertain.

Treatment

Because CLL progresses slowly, some people never require treatment. For many others, treatment may not be needed for years—when the number of lymphocytes begins to steadily increase, the lymph nodes begin to enlarge, or the number of red blood cells or platelets decreases.

Drugs used to treat the leukemia help relieve symptoms and reduce the size of the enlarged lymph nodes and spleen, but these drugs do not cure the disease. Initial treatment for many people with CLL includes chemotherapy drugs such as chlorambucil or fludarabine. Either drug can control CLL for months to many years. Eventually CLL becomes resistant to either or both of these drugs, and other drugs or antibodies (such as alemtuzumab) may be used to control 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 the formation of red blood cells). Low platelet counts are treated with platelet transfusions. Infections are treated with antibiotics, antiviral drugs, or antifungal drugs, depending on the type of microorganism. Radiation therapy is sometimes used to shrink enlarged lymph nodes or an enlarged liver or spleen if the enlargement is causing discomfort and chemotherapy is ineffective.

Finally, for some people, bone marrow (stem cell) transplantation may produce long-term disease control (and possibly a cure). Transplantation involves collecting stem cells from the person's blood before high doses of chemotherapy drugs are administered. Stem cells are unspecialized cells that transform into immature blood cells, which eventually mature to become red blood cells, white blood cells, and platelets. The collected stem cells are then returned (transplanted) to the person after the high-dose treatment. Generally, stem cell transplantation is so taxing that it is usually reserved for people who are younger than 75.

Outlook

CLL usually progress slowly. At the time CLL is diagnosed, the doctor determines how far the disease has progressed (staging) to predict how long the person is likely to survive. Staging is based on such information as number of lymphocytes in the blood and bone marrow, size of the spleen and liver, presence or absence of anemia, and platelet count.

Many people with CLL survive 10 to 20 years or longer after the diagnosis is made and usually do not need treatment in the early stages. Some may die of other causes and never need treatment for their CLL. However, among people who are anemic or who have a low number of platelets at the time CLL is diagnosed, more immediate treatment is needed, and the outlook even with treatment is less favorable. Some people with CLL develop other cancers, such as skin or lung cancers. CLL can also transform into a more aggressive type of lymphoma. Eventually, in some people with CLL, death occurs when the bone marrow can no longer produce a sufficient number of normal cells to carry oxygen, fight infections, and prevent bleeding.