Chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a type of cancer of the blood and bone marrow — the spongy tissue inside bones where blood cells are made. It’s called chronic leukemia because it progresses more slowly than acute leukemia. It’s called lymphocytic leukemia because it affects a group of white blood cells called lymphocytes, which typically fight infection.

Under normal circumstances, your bone marrow produces immature cells (stem cells) in a controlled way, and they mature and specialize into the various types of blood cells, as needed. When these cells grow old, they die naturally and are replaced by new cells, in a continuous cycle. In chronic lymphocytic leukemia, this process goes awry. The bone marrow produces abnormal lymphocytes. These cells don’t fully mature or die normally. Over time, they accumulate in large numbers and eventually crowd out other healthy cells, leaving people with chronic lymphocytic leukemia vulnerable to infection and other life-threatening problems.

Each year, about 10,000 people in the United States receive a diagnosis of chronic lymphocytic leukemia. A decade ago, doctors thought chronic lymphocytic leukemia always affected older adults and rarely posed enough risk to warrant cancer treatments, so “watchful waiting” was the treatment of choice. Today, new laboratory tests, new medications and a new understanding of chronic lymphocytic leukemia have dramatically changed the rules for treatment of this type of leukemia. Doctors now know that chronic lymphocytic leukemia can behave aggressively in some people. Although watchful waiting is still the best option for some people, new medications are helping people diagnosed with a more aggressive form of chronic lymphocytic leukemia at a younger age.

Symptoms

At first, chronic lymphocytic leukemia may cause no signs or symptoms. When signs and symptoms are present in the early phases of the disease, they are often vague and unspecific and include:

  • Fever
  • Weight loss
  • Loss of appetite
  • Lethargy and fatigue, especially during exercise
  • Night sweats

More specific signs and symptoms may emerge in the more advanced phases of untreated chronic leukemia. These signs and symptoms occur when leukemic cells crowd out properly functioning, mature blood cells. A range of problems can occur, depending on the type of blood cell affected:

  • Red blood cells. These cells carry oxygen from your lungs to all parts of your body. A shortage of red blood cells (anemia) can cause shortness of breath, fatigue, pale skin and other problems.
  • White blood cells. These infection fighters help your body ward off germs. A shortage of healthy white blood cells (leukopenia) or of a particular type of healthy white blood cells called neutrophils (neutropenia or granulocytopenia) can result in frequent infections. People with chronic lymphocytic leukemia are actually more likely to have very high white blood cell counts, but the white blood cells aren’t functioning properly, so they don’t protect against infection the way normal white blood cells do.
  • Blood platelets. These cells help prevent and control bleeding by prompting your blood to clot. A shortage of blood platelets (thrombocytopenia) can result in easy bleeding and bruising, including frequent or severe nosebleeds, bleeding from the gums, or tiny red marks caused by bleeding into the skin (petechiae).

Chronic lymphocytic leukemia can also cause bone pain, joint pain, swelling of the liver and spleen, and enlargement of the lymph nodes in the neck, underarm, stomach or groin.

In a small number of cases, chronic lymphocytic leukemia may transform into other types of lymphoma. People with chronic lymphocytic leukemia are also at increased risk of developing certain infections or a secondary cancer.

Causes

The cause of chronic lymphocytic leukemia is damage to the DNA of developing cells in the bone marrow. Your DNA is like a set of instructions for your cells, telling them how and when to grow and divide. Certain genes on your DNA called oncogenes promote cell division. Other genes, called tumor suppressor genes, slow down cell division and cause cells to die at the appropriate times.

Leukemia can occur when damage to DNA turns on oncogenes or turns off tumor suppressor genes. When this happens, blood cell production goes awry. In chronic lymphocytic leukemia, the bone marrow produces abnormal, ineffective lymphocytes. These lymphocytes accumulate in the blood and in certain organs and interfere with normal blood cell production.

Doctors and researchers don’t understand the exact mechanism that causes chronic lymphocytic leukemia or how it occurs. But they have discovered that many people with chronic lymphocytic leukemia have chromosome deletions — loss of part of one of the 23 pairs of chromosomes that make up each human cell. Some people with chronic lymphocytic leukemia have an extra chromosome or another chromosome abnormality.

The majority of cases of chronic lymphocytic leukemia aren’t inherited. However, a small percentage of people with this form of leukemia have a family history of chronic lymphocytic leukemia or lymphoma.

Unlike other forms or cancer or leukemia, chronic lymphocytic leukemia has few known risk factors. Some studies have suggested that exposure to herbicides and insecticides, such as those used in farming or those used in Agent Orange during the Vietnam War, may increase the risk of chronic lymphocytic leukemia.

In general, this type of leukemia tends to affect older adults. Most cases of chronic lymphocytic leukemia are found in people age 50 and older, and incidence increases with age.

Diagnosis

Signs of chronic lymphocytic leukemia are often discovered unintentionally, during a blood test for some unrelated condition. But your doctor may also suspect leukemia based on your symptoms.

Either way, if chronic lymphocytic leukemia is suspected you’ll need to have special analysis of your blood. In some cases, a bone marrow biopsy also will be needed. You may undergo the following diagnostic tests:

  • Blood tests. Most people with chronic leukemia have high levels of white blood cells (lymphocytosis) and sometimes not enough red blood cells. They may also have abnormal levels of platelets.
  • Bone marrow test. A bone marrow test is common for other forms of leukemia, but it’s used only for some people with chronic lymphocytic leukemia. In a bone marrow test, a doctor or nurse uses a needle to remove a sample of your bone marrow to look for leukemia cells, damage to the bone marrow and chromosome abnormalities. Usually, the sample is taken from your pelvic bone.

A doctor who specializes in diagnosing cancer and other tissue abnormalities typically examines blood or bone marrow samples under a microscope. He or she can classify blood cells into specific types based on their size, shape and other features. This helps establish the type and subtype of leukemia.

In the last decade, doctors have begun relying on additional diagnostic tests to be more certain about the diagnosis. These tests can also give doctors some idea of how aggressive an individual’s chronic lymphocytic leukemia is likely to be. Doctors and researchers now believe that there may be at least two forms of chronic lymphocytic leukemia. One kind is a smoldering, slow-moving type of leukemia that typically doesn’t require treatment. The other is a more aggressive, more serious disease. The following lab tests can confirm the diagnosis of chronic lymphocytic leukemia and help identify people with the more aggressive form:

  • Immunophenotype. Immunophenotyping helps determine whether the increased number of lymphocytes in your blood is caused by a reactive process — such as a reaction to infection or inflammation — or a cancerous process. It also helps distinguish chronic lymphocytic leukemia cells from other types of leukemia and lymphoma.
  • Cytogenetic analysis. This test detects changes in the chromosomes, such as the deletion of part of a chromosome. Special technology called fluorescent in situ hybridization (FISH) detects chromosomal abnormalities associated with chronic lymphocytic leukemia that standard chromosome testing techniques can’t detect. Cytogenetic analysis helps distinguish chronic lymphocytic leukemia from other types of leukemia or lymphoma and helps distinguish more aggressive and less aggressive forms of the disease.
  • Other tests. New lab tests are able to identify certain substances in the blood or in the cells that may indicate a more aggressive form of chronic lymphocytic leukemia. For example, high amounts of proteins known as ZAP-70, immunoglobulin mutation status or CD38 may signal a more aggressive form.

Staging
After the diagnosis is confirmed, the next step is determining the stage of the chronic lymphocytic leukemia. Most types of cancer are classified with a Roman numeral between 0 and IV, depending on the size of the tumor and how much it has spread. Because leukemia doesn’t involve a tumor, it requires a different method of classification. Doctors use two staging systems for chronic lymphocytic leukemia:

  • Rai system. Using this system, doctors classify chronic lymphocytic leukemia into five stages from 0 to IV, with higher numbers indicating more advanced stages of disease. In the Rai system, stages are determined by your platelet and red blood cell counts, as well as the presence of an enlarged spleen, liver or lymph nodes.
  • Binet system. In this system, chronic lymphocytic leukemia is classified into three stages from A to C, depending on your platelet and red blood cell counts, as well as the number of affected lymphoid regions — such as the neck lymph nodes, groin lymph nodes, spleen and liver.

The Rai system is more commonly used in the United States, while the Binet system is more commonly used in Europe.

Treatment for chronic lymphocytic leukemia

There’s no known cure for chronic lymphocytic leukemia, and the treatments can cause significant side effects for some people. In addition, many people have a slow-moving form of chronic lymphocytic leukemia that doesn’t cause symptoms for years. As a result, the most important treatment decision in chronic lymphocytic leukemia is whether or not treatment is necessary.

Unlike other forms of cancer, chronic lymphocytic leukemia doesn’t always require treatment. For older adults or people with early-stage chronic lymphocytic leukemia and few troublesome symptoms, the risks associated with the disease don’t warrant the risks and discomfort associated with treatment. In these cases, the best option is watchful waiting. If you choose this approach, your doctor will closely monitor your progress with regular blood tests and physical exams. If symptoms change or worsen, you can re-evaluate your options and change course.

Doctors typically recommend treatment for people with symptoms, repeat infections or a rapidly progressing form of the disease, which is indicated by rapid changes in leukemia cell counts. The particular form of treatment depends on such factors as your age, your overall health, the aggressiveness of the disease and the speed at which the disease seems to be progressing. Treatment options include:

  • Chemotherapy. This is the major form of treatment for chronic lymphocytic leukemia. Chemotherapy uses chemical agents to kill leukemia cells, but it also kills some healthy cells in the process. Chemotherapy medications may come in a pill form, or they may be injected directly into a vein (IV). The most common chemotherapy drugs for treating chronic lymphocytic leukemia include fludarabine (Fludara), chlorambucil (Leukeran), pentostatin (Nipent) and cyclophosphamide (Cytoxan).
  • Biological therapy. Also known as immunotherapy, biological therapy uses substances that bolster your immune system’s response to cancer. Monoclonal antibodies are one form of biological therapy. These antibodies are produced in a laboratory, but they mimic protein products found in your immune system (antibodies) that attack foreign substances (antigens) on leukemic cells. Rituximab (Rituxan) and alemtuzumab (Campath) are two monoclonal antibodies used to treat chronic lymphocytic leukemia. These medications may be combined with chemotherapy or used if chemotherapy isn’t working.
  • Bone marrow transplant. This procedure allows people with leukemia to re-establish healthy stem cells by replacing their leukemic bone marrow with leukemia-free marrow. In some cases, the healthy bone marrow is from a compatible donor (allogeneic transplant). In other cases, transplants can be done using a person’s own harvested bone marrow (autologous transplant). However, bone marrow transplant is rarely used for treatment of chronic lymphocytic leukemia because it’s appropriate only for a very select group of people.
  • Stem cell transplant. Stem cell transplant is similar to bone marrow transplant except the stem cells are collected from circulating blood (peripheral blood), rather than from the bone marrow. Like bone marrow transplant, stem cell transplant is appropriate only for a very select group of people with chronic lymphocytic leukemia.
  • Clinical trials. Some people with leukemia enroll in clinical trials to try out experimental treatments or new combinations of known therapies. Several new drugs for chronic lymphocytic leukemia are being tested in clinical trials. Other clinical trials are exploring the effectiveness of bone marrow or stem cell transplant for treatment of chronic lymphocytic leukemia.
  • Supportive treatments. Having chronic lymphocytic leukemia increases your risk of developing infections and other complications. You may need vaccinations or medications to prevent or manage particular conditions that can be associated with chronic lymphocytic leukemia.

Coping skills

Chronic lymphocytic leukemia is often characterized as a slow-moving type of cancer with few signs and symptoms in the early stages. But, if you have chronic lymphocytic leukemia, this may not seem all that reassuring.

You may experience fatigue even in the early stages of the disease. And you may not be very comforted by the term “slow-moving” when it’s followed by the word “leukemia.” Here are some tips for coping:

  • Get down to particulars. The term “leukemia” can be confusing, since it refers to a group of cancers that aren’t all that similar except for the fact that they affect the bone marrow and blood. You can waste a lot of time researching information that doesn’t apply to your kind of leukemia. To avoid that, ask your doctor to write down as much information about your specific disease as possible. Then narrow your search for information accordingly. Write down questions you want to ask your doctor before each appointment, and look for information in your local library and on the Internet. Good sources include the National Cancer Institute, the American Cancer Society and The Leukemia & Lymphoma Society.
  • Lean on family, friends and others with chronic lymphocytic leukemia. It can be tough to talk about your diagnosis, and you’ll likely get a range of reactions when you share the news. But talking about your diagnosis can be helpful. So can the practical help that often results. You may also benefit from joining a support group — in your community or on the Internet. A support group of people with the same diagnosis can be a source of useful information, practical tips and genuine encouragement.
  • Explore ways to cope with the nagging, chronic nature of the disease. If you have chronic lymphocytic leukemia, you’ll likely face ongoing tests and ongoing worries about your white blood cell count. Try to find some activities that help you relax, whether it’s yoga, exercise or gardening. Talk to a counselor, therapist or oncology social worker if you need help dealing with the emotional challenge of this chronic disease.