Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the lymphocytes, a type of white blood cell. CLL begins in the bone marrow and then travels to the blood. It may spread to the lymph nodes and other organs, including the spleen and liver.
Many different types of cancer exist, all caused by the uncontrolled growth of cells within the body. The type of cells affected and where cancer originates determine a person’s specific cancer diagnosis. Cancers affecting bone marrow and blood cells are known as leukemias.
CLL is the
This article provides an overview of CLL, including its types, symptoms, causes, diagnosis, and treatment. It also discusses the outlook for people with this condition.
CLL is a type of cancer originating in the bone marrow that affects white blood cells, known as lymphocytes. Lymphocytes are an important part of a person’s immune system. They help the body fight infection and contribute to antibody formation for lasting immunity.
CLL
Lymphocytes in CLL are less functional and have longer lifespans. They accumulate in the body and cause unusual signaling that can suppress the immune response. Lymphocyte changes in CLL can directly contribute to an increase in infections and autoimmune complications.
As a chronic leukemia, CLL develops slowly over a period of years and does not usually cause symptoms in its early stages. Acute leukemias progress rapidly, causing noticeable symptoms early on, and typically require prompt treatment.
How common is CLL?
Research suggests that CLL accounts for up to
The
There are two subsets of CLL. One subset grows slowly, while the other grows more rapidly and is more serious. Doctors can identify them by the genetic characteristics of their IGHV gene:
- IGHV-mutated CLL (M-CLL): slow growing
- IGHV-unmutated CLL (U-CLL): fast growing
The leukemia cells of the two types of CLL look alike, but those of the slower-growing type have low amounts of proteins called CD38 and ZAP-70.
Low levels of these proteins generally cause the cancer to grow more slowly. Doctors can check for these proteins to get an idea of a person’s outlook, which will likely be more positive if the cancer is slow to progress.
The symptoms of CLL can vary from mild to severe, and some individuals may have more symptoms than others. In the early stages of CLL, no obvious symptoms may be present, but signs and
Less common symptoms can include:
- bone pain
- anemia
- shortness of breath
- red or purple spots on the skin (petechiae)
- swelling in the extremities (edema)
- jaundice
Doctors do not know the cause of CLL. However, about 10% of people with CLL have a family history of the condition.
Risk factors for CLL
- Age: The risk increases with age. Of those with the condition, 9 in 10 are over the age of 50 years. Natural age-related genetic changes, immune system decline, and environmental exposures over time may play roles in the link between CLL and age.
- Family history: People who have parents, children, or siblings with cancer have more than double the risk of developing CLL. This suggests that a hereditary and genetic component of CLL passes down through families.
- Genetics: There is an association between certain genetic alterations and CLL. According to a
2017 review , 80% of people with CLL carry at least 1 out of 4 common chromosomal alterations: deletion 13q14, deletion 11q22-23, deletion 17p12, and trisomy 12. Deletion 13q14 is the most frequent genetic alteration in CLL. - Exposure to certain chemicals: Environmental exposures can contribute to genetic alterations and how genes express themselves. Some research links CLL to exposure to Agent Orange, a herbicide the military used during the Vietnam War. Other studies suggest that long-term exposure to some pesticides may increase the risk of developing CLL.
- Sex: This leukemia is slightly more common in males than in females. The reasons for this are unclear.
- Race and ethnicity: This leukemia is more prevalent in parts of Europe and North America than in Asia. As Asian people living in the United States have the same risk as those living in Asia, experts believe the risk factor is genetic rather than environmental.
The disease progression of CLL, as well as treatments used to manage this condition, can lead to other health complications
- Increased susceptibility to infection: CLL can suppress the body’s immune response, increasing the risk for viral and bacterial infections.
- Bone marrow failure: As a cancer originating in the bone marrow, CLL can cause too-high lymphocyte levels that crowd the bone marrow’s ability to produce other cells, like red blood cells.
- Bone marrow suppression: Treatments such as chemotherapy to control lymphocyte production in CLL may negatively affect overall bone marrow function.
- Autoimmune disorders: CLL may contribute to conditions of autoimmunity, such as hemolytic anemia or immune thrombocytopenia, where the body attacks its own blood cells.
- Immune suppression: Certain CLL treatments targeting lymphocytes can further weaken the body’s natural immune response.
- Secondary cancers: CLL may prevent the immune system from effectively fighting other types of cancer in the body.
- Aggressive lymphoma: Approximately 2% to 10% of people diagnosed with CLL experience excessive genetic changes that lead to the development of Richter’s syndrome, an aggressive form of large cell lymphoma.
- Decreased quality of life: As CLL progresses, symptoms and treatment side effects can become impairing and may negatively affect important areas of function and interpersonal relationships.
Doctors may use a range of tests to diagnose CLL,
- Health history and physical exam: A doctor will ask a person about their health conditions and treatments. They will also check for signs of CLL, such as enlarged lymph nodes.
- Complete blood count test: This test measures the number of red blood cells and platelets, which are the cell fragments involved in blood clotting. It also measures the number and types of white blood cells and the amount of hemoglobin, which is a protein in red blood cells that carries oxygen.
- Blood chemistry studies: These measure certain substances that tissues and organs release into the blood. A lower or higher amount may be a sign of leukemia.
- Beta-2-microglobulin testing: This test measures a small protein present on the surface of various cells, including lymphocytes. A higher amount may indicate that the cancer is more difficult to treat.
- Lactate dehydrogenase testing: Doctors use this to measure one of a group of enzymes in the blood. A higher amount may suggest tissue damage and cancer.
- Flow cytometry: Flow cytometry measures the number of cells in a sample and their characteristics, such as shape, size, and the presence of tumor markers.
- Gene mutation testing: Doctors can look for changes in certain genes to understand a person’s likely outlook.
- Fluorescence in situ hybridization (FISH): FISH counts chromosomes or genes in cells and tissues, which helps a doctor diagnose cancer and decide on the best treatment approach.
- Serum immunoglobulin testing: This test measures specific blood antibodies. It helps diagnose cancer and shows whether treatment is effective.
Staging and rating systems in cancer allow doctors to determine disease progression and predict outcomes. Staging systems traditionally gauge the progression of a condition, while rating systems tend to evaluate clinical markers to assess potential outcomes (outlook).
While doctors can use several rating and staging systems in CLL, the Rai and Binet staging systems are among the
Rai staging is more prevalent in the United States, and Binet staging is seen more often in Europe.
Rai staging system
Named after Dr. Kanti Rai and other founding colleagues, the Rai staging system classifies CLL into stages based on clinical markers, such as lymphocyte count, organ enlargement, and anemia or thrombocytopenia (too-low platelet count).
Low risk
- Stage 0: high lymphocyte count but no other signs
Intermediate risk
- Stage 1: high lymphocyte count and enlarged lymph nodes
- Stage 2: high lymphocyte count and enlarged liver or spleen
High risk
- Stage 3: high lymphocyte count and anemia
- Stage 4: high lymphocyte count and thrombocytopenia
Binet staging system
French hematologist Paul Binet developed the Binet staging system. It stages CLL by the number and extent of lymphatic structures affected.
- Stage A: fewer than three areas of lymphoid involvement, such as enlarged lymph nodes
- Stage B: three or more areas of lymphoid involvement
- Stage C: any number of lymphoid structures involved with anemia and/or thrombocytopenia present
CLL International Prognostic Index (CLL-IPI)
The CLL-IPI combines Rai or Binet staging with physiological characteristics and clinical markers to categorize CLL into four outcomes, or outlook, groups.
A person’s score comprises a variation of the following:
- TP53 gene deleted or mutated: 4 points
- Unmutated IGHV:2 points
- Serum beta-2 microglobulin concentration > 3.5 milligrams per liter: 2 points
- Rai Stage 1 to 4 or Binet Stage B to C: 1 point
- Person over 65 years: 1 point
Treatment guidelines are then as follows:
- Low risk — score of 0 to 1: Do not treat.
- Intermediate risk — score of 2 to 3: Do not treat unless highly symptomatic.
- High risk — score of 4 to 6: Treat unless there are no symptoms.
- Very high risk — score of 7 to 10: If treating, use novel agents or a clinical trial instead of chemotherapy.
Doctors can treat CLL in
Most common treatments
The treatments that doctors are more likely to recommend include:
Targeted therapy
These medications target specific changes in cells that cause them to turn into cancer. Doctors
Chemotherapy
Chemotherapy attacks fast-growing cells, including cancer cells. The
Monoclonal antibodies
Monoclonal antibodies are synthetic versions of immune system proteins that help the immune system attack cancer by binding to proteins on cancer cells. A
Supportive care
Aside from treatment to remove cancer, an individual may need supportive care, which can address problems related to medications and the effects of cancer. Supportive care can
Stem cell transplants
A stem cell transplant involves receiving higher dosages of chemotherapy and possibly radiation therapy to treat the cancer. Afterward, a person receives a transplant to restore bone marrow. Doctors
Less common treatments
Other treatment options include:
Leukapheresis
Although doctors
Surgery
As leukemia cells spread widely, doctors
Radiation therapy
This treatment uses high energy rays to destroy cancer cells. Doctors
When a doctor finds no signs of cancer following treatment, it is called complete remission. However, at some point, the cancer
According to a 20-year research initiative presented in 2023, long-term remission in CLL is possible and common, with most people in the research achieving remission for 10 years or longer.
The relative 5-year survival for people with this leukemia between 2014 and 2020 was
Although CLL is rarely curable, most people with the condition live with it for many years. Consequently, most individuals receive treatment on and off for an extended period.
It is important for people to attend all follow-up appointments so doctors can monitor their condition before, during, and after treatment. Some people may also wish to ask their doctor for a survivorship care plan, which may include:
- a schedule for follow-up tests and exams
- a list of possible late side effects of treatment
- diet and exercise recommendations
After the end of treatment, individuals should maintain their health insurance because they may need further treatment at a later date. They should also keep medical records up to date in case they need to consult a new doctor who is unfamiliar with their medical history.
Although doctors
- quitting smoking, if applicable
- eating a healthy, balanced diet
- exercising regularly
- aiming for a moderate weight
Lastly, symptoms of depression and anxiety are typical with this condition, so it is beneficial for people to seek support from family, friends, and professional counselors.
Chronic lymphocytic leukemia (CLL) may cause various signs and symptoms, such as enlarged lymph nodes, fever, and tiredness. The cause remains unknown, but risk factors include being an older adult and having a family history of the condition.
The standard treatment consists of a targeted therapy in pill form. Compared with other cancers, the outlook for people with CLL is generally good — the disease has a relative 5-year survival rate of 88.5% for people of all ages.