Chronic lymphocytic leukemia (CLL)

ALSO KNOWN AS: Chronic lymphoid leukemia

RELATED CONDITIONS: Acute lymphocytic leukemia, acute myeloid leukemia, chronic myeloid leukemia

DEFINITION: Chronic lymphocytic leukemia (CLL) is a cancer of the white blood cells. A lymphocyte is a type of white blood cell made in the bone marrow that helps fight infection. For unknown reasons, the bone marrow begins to make lymphocytes that develop abnormally, causing this fast-growing type of cancer. Regarding this disease name, "chronic" means the disease does not progress as rapidly as acute lymphocytic leukemia.

Risk factors: There are few risk factors for CLL. Past research has concluded that environmental factors do not affect the risk of developing CLL. However, research is ongoing on whether exposure to herbicides and insecticides increases the risk of CLL. About half the people who develop CLL have chromosomal abnormalities, such as deletions on a chromosome or an extra chromosome. People with close relatives who have CLL have a slightly increased risk of developing this disease. Risk increases with age; patients with CLL are rarely under the age of forty-five and are generally over the age of sixty. Men are more likely to develop CLL than women, and whites and those of Russian Jewish or Eastern European Jewish descent are more likely to develop it than those of other racial and ethnic backgrounds.

Etiology and the disease process: CLL starts in a single white blood cell (lymphocyte). These CLL cells multiply and crowd out the normal white blood cells. The CLL cells accumulate in the bone marrow, but they do not stop routine blood cell production, much like some other types of leukemia. Slow-growing CLL may cause only minimal changes in the blood for years. Some patients begin to produce an antibody during the CLL disease process that works against their body's red blood cells and causes a severe type of anemia. In a small number of CLL patients, the disease changes and begins to act like a more aggressive type of lymphoma or leukemia. In a small number of CLL patients, CLL begins to act like acute lymphocytic leukemia (ALL) throughout the disease process.

Incidence: An estimated 20,700 new cases of CLL are expected to be diagnosed in the United States in 2024, resulting in 4,440 deaths. Most with CLL are over fifty, with an average age of 70. The average person's lifetime risk is approximately 0.57 percent, with the risk being slightly higher for men.

Symptoms: Symptoms of CLL usually develop slowly. Patients may find out they have this type of slow-growing cancer after getting blood tests for another condition. Symptoms may include:

• anemia,
• bleeding easily,
• bone pain,
• bruising easily,
• fever,
• joint pain,
• loss of appetite,
• night sweats,
• pain or a feeling of fullness below the ribs,
• shortness of breath,
• swollen liver,
• swollen lymph nodes,
• swollen spleen,
• tiredness,
• unexplained or repeated infections,
• and weight loss.

Screening and diagnosis: There is no screening test for CLL. Blood and bone marrow tests are necessary to diagnose CLL. These tests look for abnormal lymphocyte cells. Bone marrow aspirate test or biopsy are two possible tests. The bone marrow aspirate test looks for abnormal cells in the bone marrow and can also be used for other types of analysis. A bone marrow biopsy can show how much disease is already in the bone marrow. The results of these tests help determine which type of drug therapy to use and how long treatment should last. Another test that may be performed is immunophenotyping, which helps determine whether the increased lymphocytes in the blood are monoclonal (came from a single malignant cell). This can help distinguish CLL from other types of diseases that cause increased lymphocytes in the blood.

Depending on where the cancer started and the testing results, CLL may be categorized into B-cell CLL (the most common type), T-cell CLL (which generally behaves more like other T-cell cancers than CLL), or NK-cell CLL. B-cell CLL may be divided into subtypes based on whether genetic mutations occur. As these mutations may affect how rapidly the disease progresses, this further division may help doctors determine treatment and which patients will benefit from earlier treatment. These subdivisions also give a general idea of the progression and outcome of the disease, such as what effect the disease will have on marrow and blood cell development and what other organs, such as kidneys, bowels, or liver, may be affected. Researchers are investigating whether these subdivisions of CLL are actually different types of cancer.

Staging of CLL involves evaluating the number of CLL cells, whether the liver, lymph nodes, or spleen are enlarged, and whether the red blood cell or platelet counts are low. In the Rai system, used commonly in the United States, CLL is divided into five stages:

• Stage 0: Large numbers of lymphocytes in the blood but no other symptoms
• Stage I: Large numbers of lymphocytes in the blood and enlarged lymph nodes
• Stage II: Large numbers of lymphocytes in the blood, enlarged liver or spleen, possibly enlarged lymph nodes
• Stage III: There are large numbers of lymphocytes in the blood, too few red blood cells (anemia), and possibly enlarged lymph nodes, liver, or spleen.
• Stage IV: Large numbers of lymphocytes in the blood, too few platelets, possibly too few red blood cells, and perhaps enlarged lymph nodes, liver, or spleen

Treatment and therapy: Patients diagnosed with CLL may not need treatment immediately. They may have had good health for several years without any treatment. However, doctors will want to closely follow patients with CLL to ensure that the CLL is not worsening. This allows patients to avoid the side effects of treatment until treatment is necessary.

However, some patients will need treatment near the time of diagnosis because these patients have had the disease for some time and it is progressing or because they have a faster-growing type of CLL. Treatment may become necessary when the number of CLL cells rapidly increases, the number of normal cells decreases, anemia worsens, the lymph nodes or spleen enlarges, or symptoms become bothersome to patients.

Treatment involves:

• slowing the growth of CLL cells,
• keeping patients well enough to carry out daily activities, and
• protecting patients from infections because the abnormal white cells cannot fight infection.

CLL is usually treated with chemotherapy or monoclonal antibody therapy. These therapies involve using certain drugs or combinations to kill abnormal lymphocytes.

A bone marrow or cord blood transplant may help some CLL patients. A transplant is a high-risk procedure, however, and probably will not be used unless a patient has a fast-growing type of CLL, is younger than fifty-five years of age, and has a close relative who is a good transplant match. Older patients or patients with slow-growing CLL are not good transplant candidates.

CLL is not usually treated with radiation therapy. However, radiation may be used if a large mass of lymphocytes blocks an essential body part, such as the kidneys, stomach, intestines, or throat. In a small number of CLL patients, surgery to remove the spleen (splenectomy) can help relieve pressure if the spleen is filled with too many CLL cells.

If patients with CLL have problems fighting infections, they may be treated with antibiotics. If infections become chronic, patients may be treated with injections of a protein found in the blood that fights infections (immunoglobulin).

Follow-up treatment for CLL involves regular doctor visits and continuing lab tests to make sure the CLL cells are not beginning to increase rapidly. These doctor visits also help find any side effects from treatment. Patients who have had CLL are at increased risk for developing some other cancers, such as lung, colon, or skin cancer, and patients should be screened for these conditions during follow-up visits.

Prognosis, prevention, and outcomes: There is no cure for CLL or known way of preventing the disease. However, many patients, especially those with slow-growing forms of this disease, may live for many years in good health. Survival rates range from one year to more than twenty or thirty years, depending on the stage and form of the disease. For 2014-2020, the five-year survival rate of CLL patients was 88.5 percent.

New strategies and treatments are emerging in the mid-2020s. These include new drugs targeted at specific structures within cancer cells. Strategies are designed where combinations of treatments are employed in tandem. Vaccines are used not simply in preventative roles but to stimulate the body's immune system to search out, detect, and destroy cancer cells.

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