Chronic Lymphocytic Leukemia (CLL)

What is Adult Chronic Lymphocytic Leukemia?

Adult chronic lymphocytic leukemia (CLL) is a type of cancer in which there is an accumulation of abnormal white blood cells (or lymphocytes) in the blood and bone marrow. Although rare compared to other types of cancer such as colon, lung, prostate, or breast cancer, about 10,000 new cases of CLL are expected in the United States this year.

CLL is the most common type of leukemia in adults. The average age at diagnosis is 70, and CLL rarely occurs in people under 40. The physicians at Rocky Mountain Cancer Center (RMCC) and the Rocky Mountain Blood and Marrow Transplant Program (RMBMTP) are specialists in the care of patients with CLL.

CLL is a disease in which there is an accumulation of abnormal white blood cells in the blood and bone marrow. In chronic lymphocytic leukemia, the leukemia cells mature, but not completely; in acute lymphocytic leukemia, the cells do not mature properly. In both conditions, the leukemia cells build up and crowd out normal cells. These leukemia cells cannot perform their normal infection-fighting functions and interfere with the production of other blood cells (although not as severely as in acute lymphocytic leukemia), leading to immune deficiency, bleeding, swollen lymph nodes and other conditions.

What causes CLL?

CLL is caused by an acquired (not inherited) injury to the DNA of a single cell in the bone marrow which becomes abnormal. The result is the uncontrolled growth of lymphocytic cells in the bone marrow and an increase in the concentration of lymphocytes in the blood. Unlike other forms of leukemia, CLL is not connected to high-dose radiation or benzene exposures. Although CLL is not hereditary, the disease does seem to run in families, and the risk increases with age. According to the American Cancer Society, research studies suggest that chemicals used in farming (such has herbicides and insecticides) and Agent Orange (an herbicide used during the Vietnam War) may increase the risk of CLL.

How is CLL diagnosed?

The symptoms of CLL, which usually develop gradually, include tiring easily and shortness of breath when physically active. The patient may lose weight and have frequent infections of the skin, lungs, and kidneys. There may be a feeling of pain or fullness in the belly (especially after eating a small meal). Early in the disease CLL may have few symptoms, and the disease is often detected during a “routine” medical examination when an elevated white blood cell count is found in the blood. Doctors use tests that examine the blood and sometimes bone marrow to detect and diagnose CLL, including:

• Physical examination and history


• Complete blood count


• Sometimes a bone marrow aspiration and biopsy (looking for abnormal cells)


• Cytogenetic or “FISH” analysis to analyze changes in the DNA of the CLL cell


• Immunophenotyping (identifying cells based on the types of antigens or markers on the surface of the cell to diagnose CLL)

Blood and bone marrow cells usually reveal high levels of white cells and an increased proportion of lymphocytes in the marrow. Low platelet counts and low red cell counts may be present, but are usually only slightly decreased in the early stages of CLL.

Doctors now think there are most likely two kinds of CLL. One kind is very slow growing and rarely needs to be treated. The average survival for people with this kind of CLL is around 25 years. Another kind is faster growing and a more serious disease, with an average survival rate of six to eight years. The leukemia cells from these two types look alike, but can be distinguished by the presence of certain substances in the blood reflecting changes in the genes of the CLL cell. One test looks for the protein Zap-70; another test looks for a substance called CD38. The CLL cells of people with the more serious form of CLL will have high amounts of Zap-70 and CD38. The elevated level of Zap-70 and/or CD38 usually indicates a less mature, or more aggressive, form of CLL.

Once CLL has been diagnosed, tests may be conducted to see if the cancer has spread to other parts of the body. The spread of most cancers is usually described as stages. In CLL, the staging is separated into low, intermediate, and high-risk categories. Stage 0 is considered low risk; stages I and II are considered intermediate risk; and stages III and IV are considered high risk.

• Stage 0 – the lymphocyte count in the blood is too high and the cells all have the same chemic pattern on special testing. The lymph nodes, spleen and liver are not enlarged, and the red blood cell and platelet counts are near normal.


• Stage I – the lymphocyte count in the blood is too high, and the lymph nodes are enlarged. The spleen and liver are not enlarged, and the red blood cell and platelet counts are near normal.


• Stage II – the lymphocyte count in the blood is too high, and the liver or spleen are enlarged (with or without enlarged lymph nodes). The red blood cell and platelet counts are near normal.


• Stage III – the lymphocyte count in the blood is too high, and the patient has anemia (too few red blood cells). The lymph nodes, liver and spleen may or may not be enlarged. Platelet counts are near normal.


• Stage IV – the lymphocyte count in the blood is too high and there are too few platelets. The patient may or may not have anemia or enlarged lymph nodes, liver and spleen.

Many experts feel that the type of CLL is more important than the stage of CLL in determining which treatments should be used on an individual basis. This is accomplished by using tests to determine the presence of Zap-70 and CD38 in the leukemic cells or “FISH” tests to look at the DNA changes.

What are the treatment options?

There are six types of standard treatment used for CLL: chemotherapy, biologic therapy, radiation therapy, surgery (usually to remove the spleen), and stem cell transplantation. Other types of treatment are being tested in clinical trials. Treatments for people with CLL vary, depending on the stage of the disease and if the leukemia is causing any symptoms.

Low-risk CLL: The prognosis for this group is very good, with an average survival rate of 20 to 25 years. The usual approach is to give no initial treatment; frequent follow-up examinations are recommended, and treatment should be considered if the leukemia is progressing or if there are symptoms. Reasons for starting treatment might include: fever, sweats, very large lymph nodes, large spleen, anemia, too many infections and low platelet count. The initial treatment is usually chemotherapy.

Intermediate and high-risk CLL: Patients in these categories who do not have symptoms may not need treatment right away. Frequent follow-up examinations are recommended to look for signs of progression and new symptoms. Recommended treatment is chemotherapy. If needed, a splenectomy (surgery to remove the spleen) is performed. Stem cell transplantation is another option.

The drugs or regimens used most often to treat CLL are:

1. Fludarabine


2. Chlorambucil


3. Cyclophosphamide


4. Rituximab


5. Alemtuzumab (Campath)


6. CHOP


7. CVP


8. Allogeneic Transplant

Allogeneic transplants used to be done infrequently for CLL. Using newer techniques studied and developed by two of our physicians, Drs. Maris and McSweeney, this option is becoming a very effective treatment for the more aggressive forms of CLL.