Chronic Lymphocytic Leukemia

Signs and Symptoms

Chronic lymphocytic leukemia (CLL) is a disorder in which the lymphocytes lose their normal ability to die and end up accumulating over time. At first, the cells increase only in the blood, but over years they also increase in the lymph nodes, liver, spleen and bone marrow.

Many patients have no symptoms at the time of diagnosis, except for an elevated white blood cell count. Some patients will notice fatigue or enlargement of lymph nodes or fullness in the abdomen due to an enlarged spleen.

When CLL becomes more advanced and begins to replace normal bone marrow, low blood counts can result in anemia and infections. CLL increases a person's risk of infection because of low production of antibodies (gamma globulins) that help fight bacteria. In 5 percent to 10 percent of cases, CLL causes the destruction of the patient's own red blood cells and/or platelets through an "autoimmune" process. Destruction of platelets is called immune thrombocytopenic purpura (ITP), and destruction of red blood cells is called autoimmune hemolytic anemia (AHA).

Diagnosis

Chronic lymphocytic leukemia (CLL) is diagnosed through the detection of a high white blood cell count composed primarily of small lymphocytes. The diagnosis is confirmed by "immunophe-notyping" (flow cytometry) that shows coexpression of the markers CD19 and CD5. CLL is the one type of leukemia for which there is a formal staging system:

• RAI Stages 0 to I -- During this early stage of the disease, there is an elevated lymphocyte count and enlarged lymph nodes.

• RAI Stage II -- In the intermediate stage the spleen becomes enlarged.

• RAI Stages III to IV -- In the advanced stage of the disease, bone marrow function is disturbed and there is a significant decrease in red blood cell and platelet counts.

In 5 percent to 10 percent of cases, CLL can transform to an aggressive lymphoma. This is called Richter's syndrome.

Treatment

Most patients with early-stage chronic lymphocytic leukemia (CLL) do not need any treatment when the disease is first diagnosed. These patients will live 10 to 15 years on average, and early treatment offers no advantage. Treatment should start when the patient either has an advanced form of the disease or has an intermediate stage with significant symptoms, very enlarged lymph nodes or a rapid increase in the lymphocyte count (doubling in less than 12 months).

Chemotherapy

The most common treatment for CLL is the chemotherapy drug fludarabine. This is given intravenously (through an IV) five days a week once a month for four to six months. Although the schedule for fludarabine is rather inconvenient, it only causes modest side effects, such as fatigue. Most patients will have a good response to this treatment and remain in remission without further treatment for two to three years. Chlorambucil, an oral chemotherapy drug, may be used instead of fludarabine, especially for elderly or frail patients.

Investigational Therapies

There are a number of new treatments currently being tested, including:

• The use of other chemotherapy drugs, such as cyclophos-phamide and Cytoxan, in combination with fludarabine to see whether this increases the effectiveness of treatment

• The addition of antibody treatment with rituxirnab (Rituxan)

• The use of the experimental antibody Campath IH, which appears to be another effective form of treatment

In addition, allogeneic stem cell transplantation, also called bone marrow transplantation, can be used to potentially cure CLL. However, this therapy is only used to treat the occasional young patient with aggressive CLL, since most patients with CLL live so long that the risk of transplant can seldom be justified.