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Chronic Lymphocytic Leukemia (CLL)


Some people with chronic lymphocytic lymphoma (CLL) experience a feeling of abdominal fullness, unexplained weight loss, and a sense of fatigue. Other people never experience symptoms; they learn that they have the condition when their doctor offers them a blood test to monitor their overall health or check for another condition. In both cases, blood tests may confirm that people have CLL, a form of leukemia that mainly affects older adults.

About 21,000 people are diagnosed with CLL in a given year in the United States. CLL is the most commonly diagnosed form of leukemia that affects adults, accounting for 25 to 30% of all leukemia diagnoses in the U.S. People are typically diagnosed after age 40, although it’s most common among adults aged 70 and older.

Many people may not need treatment when they are diagnosed with CLL; doctors may suggest a strategy of “watchful waiting” for certain individuals.

“Most people diagnosed with CLL can be initially managed with active surveillance for months to many years,” says Smilow Cancer Hospital oncologist Scott Huntington, MD, MPH, MSc. “During this active surveillance phase, we monitor for changes in blood work, new lymph nodes or swelling, or a change in pace of their CLL progression. We aim to begin CLL therapy prior to the development of significant symptoms or complications. While CLL was commonly treated with chemotherapy in the past, most individuals now receive orally administered therapies with excellent results. We are fortunate to have several non-chemotherapy treatment options for CLL, with therapy ultimately tailored to each patient’s CLL characteristics and individual preferences.”

What is chronic lymphocytic leukemia?

CLL is a type of blood cancer that occurs when certain white blood cells, known as B cells, multiply uncontrollably.

In healthy people, white blood cells are produced in the bone marrow; they help the body’s immune system fight diseases and infections to stay healthy. In CLL, the white blood cells known as B cells don’t develop properly in the bone marrow. The cells look normal, but they don’t function properly, so they’re less effective at fighting disease. These abnormal white blood cells multiply uncontrollably and live longer than they should, gradually crowding out healthy blood cells, including red blood cells, platelets, and other white blood cells.

Eventually, the abnormal white blood cells leave the bone marrow, spreading to the lymph nodes and circulating throughout the body in the bloodstream. While these cancer cells are typically not aggressive or dangerous themselves, they can accumulate to a high degree and impact healthy tissue, leading to inflammation, reduced immune system, and low blood counts (anemia and thrombocytopenia). Often, the abnormal white blood cells congregate in the spleen and liver, where their presence may cause these organs to become enlarged.

What causes chronic lymphocytic leukemia?

Doctors do not yet know what causes CLL, although they have identified certain factors which may increase a person’s risk, including past exposure to Agent Orange during the Vietnam War.

Experts also believe that this type of leukemia may be inherited in a small subset of patients, although they haven’t yet identified all of the genes linked to the condition.

What are the symptoms of chronic lymphocytic leukemia?

Many people who have CLL don’t experience any symptoms; it’s not uncommon to have this type of cancer diagnosed after routine bloodwork results show elevated levels of white blood cells.

Those who do have symptoms may experience:

  • Fatigue
  • Fever
  • Chills
  • Swollen lymph nodes
  • Unexplained weight loss
  • Abdominal pain
  • Abdominal fullness
  • Loss of appetite
  • Night sweats
  • Anemia
  • Unexplained bruising or bleeding
  • Nosebleeds
  • Bleeding gums
  • Enlarged spleen or liver

What are the risk factors for chronic lymphocytic leukemia?

People may be at greater risk of CLL if they are:

  • Male
  • Age 70 or older
  • Relative who was diagnosed with this type of cancer

Exposure to certain chemicals may increase the risk of CLL:

  • Agent Orange or other herbicides that were used by the military
  • Insecticides

How is chronic lymphocytic leukemia diagnosed?

Doctors are able to diagnose CLL after taking a medical history, doing a physical examination, and ordering diagnostic blood tests. A bone marrow biopsy may also be helpful for some.

A doctor will ask about any symptoms, including fatigue, unexplained weight loss, and a feeling of abdominal fullness. The doctor will then ask about medical history, including other health conditions that would influence CLL treatment selection. The doctor will also ask if anyone in the family has been diagnosed with CLL.

During a physical examination, a doctor may look for swollen lymph nodes, abdominal discomfort, and unexplained bruises on the body.

When doctors suspect CLL, they send patients for bloodwork. Tests include:

  • Complete blood count(CBC), which checks to see if there are normal levels of white blood cells, red blood cells, and platelets.
  • Flow cytometry, which is done when leukemia cells are detected in the blood; dye is added to the blood sample to determine whether the cells present in the sample are indicative of CLL or of another type of leukemia, based on specific markers on the surface of leukemia cells.
  • Genetic testing of blood-containing leukemia cells, which may confirm the presence of certain gene mutations or proteins that are present when an individual has CLL.

How is chronic lymphocytic leukemia treated?

CLL progresses slowly in many people. Some may not need treatment upon diagnosis, particularly if they don’t have symptoms. Doctors may monitor their health regularly and recommend treatment when an individual experiences symptoms or disease complications. Early treatment—before it is deemed necessary—hasn’t been shown to be more effective than waiting until treatment is appropriate.

When treatment is necessary, people may receive:

  • Chemotherapy, which helps to kill cancer cells. People may receive two or more chemotherapy drugs at a time to treat CLL.
  • Immunotherapy treatments, known as monoclonal antibodies, which help to activate the immune system to fight and kill cancer cells. Chemotherapy may bebb combined with monoclonal antibodies.
  • Targeted therapy, which targets specific proteins within CLL cells to destroy them without killing healthy surrounding cells.
  • Corticosteroids, which may be useful when treatment CLL related autoimmune complications.
  • Radiation therapy, in rare instances, which may help to alleviate symptoms from an enlarged spleen or lymph nodes.
  • Stem cell transplant, which may cure CLL, involves destroying leukemia cells with high-dose chemotherapy or radiation, then reintroducing healthy blood-producing stem cells. This treatment isn’t offered to patients who respond to other treatments, and given the advances in other CLL treatment options, is rarely used for CLL at this time.

What is the outlook for people with chronic lymphocytic leukemia?

About 87% of people who are diagnosed with CLL survive 5 years or longer. Survival rates have improved in recent years as treatments have become more effective.

Having CLL significantly increases the chances that a patient will develop another form of cancer, such as skin, breast, or lung cancer. Up to 10% of people with CLL may develop an aggressive form of lymphoma, a cancer of the lymphatic system.

What makes Yale unique in its treatment of chronic lymphocytic leukemia?

"The last decade has brought considerable advancements in the treatment of CLL. We now have numerous non-chemotherapy treatment options, and therapy selection is increasingly complex,” says Dr. Huntington. “The CLL specialists at Yale take great care in educating patients and their families about all available options before helping select an optimal individualized treatment plan. While present-day CLL therapies are already excellent, CLL treatments are improving at such a rapid pace that we have come to expect better-tolerated and more effective therapies every year. Through clinical trials at Yale, many of our CLL patients have access to these next-generation and innovative treatment options.”