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Leukemia - Chronic Lymphocytic - CLL - Overview

This section has been reviewed and approved by the Cancer.Net Editorial Board, 07/2014

ON THIS PAGE: You will find some basic information about this disease and the parts of the body it may affect. This is the first page of Cancer.Net’s Guide to Chronic Lymphocytic Leukemia. To see other pages, use the menu on the side of your screen. Think of that menu as a roadmap to this full guide.

About leukemia

Leukemia is a cancer of the blood. Leukemia begins when normal blood cells change and grow uncontrollably. Chronic lymphocytic leukemia (CLL) is a cancer of the lymphocytes, a type of white blood cell involved in the body’s immune system. In some people with CLL, the disease grows and progresses slowly, and it may take years for symptoms to appear or for treatment to be needed. In fact, some patients may never need treatment for their CLL. In other patients the disease grows more quickly and needs treatment sooner.

About lymphocytes

Lymphocytes circulate in the bloodstream and are made in the lymph nodes, spleen, thymus, and bone marrow. Bone marrow is the spongy, red tissue in the inner part of the large and flat bones. There are three different types of lymphocytes: T cells, B cells, and natural killer (NK) cells. Generally, T cells fight infections by triggering other cells in the immune system and by destroying infected cells, B cells make antibodies, and NK cells fight microbes and cancer cells.  

About CLL

In people with CLL, the abnormal cells crowd other types of cells in the bone marrow, preventing the production of red blood cells that carry oxygen, other types of normal white blood cells, such as neutrophils or granulocytes that fight infection, and platelets that are needed for clotting. This means that people with CLL may have anemia from low levels of red blood cells, are more likely to get infections because they do not have enough white blood cells, and bruise or bleed easily because of a low level of platelets.

There are two general types of CLL, and it is important for doctors to find out whether the disease is caused by the overgrowth of T cells or B cells. The T-cell type of CLL is now called T-cell prolymphocytic leukemia and much less common than the B-cell type of the disease. About 1% of people with CLL have the T-cell type. More than 95% of people with CLL have the B-cell type.

Most often, CLL is diagnosed when too many abnormal lymphocytes are found in the blood, also known as lymphocytosis.  However, the same disease can occur when the abnormal lymphocytes are mostly in the lymph nodes but not in the blood. This is called small lymphocytic lymphoma, but it behaves very similarly to CLL.

Learn more about other, rare types of chronic T-cell leukemia and types of B-cell leukemia.

Looking for More of an Overview?

If you would like additional introductory information, explore these related items. Please note that these links take you to other sections on Cancer.Net:

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Leukemia - Chronic Lymphocytic - CLL - Statistics

This section has been reviewed and approved by the Cancer.Net Editorial Board, 07/2014

ON THIS PAGE: You will find information about how many people are diagnosed with this type of leukemia each year and some general survival information. Remember, survival rates depend on several factors. To see other pages, use the menu on the side of your screen.

This year, an estimated 14,620 people of all ages (8,140 men and 6,480 women) in the United States will be diagnosed with CLL. It is the most common type of leukemia diagnosed in adults, particularly older adults. CLL is rare in children.

It is estimated that 4,650 deaths (2,830 men and 1,820 women) from CLL will occur this year.

The survival rate for people with CLL varies widely according to the stage of the disease (see Stages.) The five-year survival rate is the percentage of people who survive at least five years after the cancer found. Overall, the combined five-year survival rate of people with all stages of CLL is about 84%.

Cancer survival statistics should be interpreted with caution. These estimates are based on data from thousands of people with this type of cancer in the United States each year, so the actual risk for a particular individual may be different. It is not possible to tell a person how long he or she will live with CLL. Because the survival statistics are measured in five-year intervals, they may not reflect recent advances made in the treatment or diagnosis of this cancer. Learn more about understanding statistics.

Statistics adapted from the American Cancer Society's publication, Cancer Facts and Figures 2015.

The next section in this guide is Medical Illustrations and it offers drawings of body parts often affected by this disease. Or, use the menu on the left side of your screen to choose another section to continue reading this guide.  


Leukemia - Chronic Lymphocytic - CLL - Risk Factors

This section has been reviewed and approved by the Cancer.Net Editorial Board, 07/2014

ON THIS PAGE: You will find out more about the factors that increase the chance of developing CLL. To see other pages, use the menu on the side of your screen.

A risk factor is anything that increases a person’s chance of developing cancer. Although risk factors often influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and talking about them with your doctor may help you make more informed lifestyle and health care choices.

The cause of CLL is unknown. There is no evidence that exposure to radiation, chemicals, or chemotherapy increases a person’s risk of developing CLL. However, the following factors may raise a person’s risk of developing CLL:

Family history. Although it is uncommon, more than one close relative may develop CLL or some other lymph-related cancer. People with a first-degree relative with CLL, such as a parent, sibling, or child, are two to four times more likely to develop the disease. In order to learn more about families with a history of CLL, there is a registry of such families at the National Cancer Institute.

Age. CLL is most common in older adults, is rare in young adults, and hardly ever develops in children. About 90% of people diagnosed with CLL are older than 50. The average age at diagnosis is close to 70.

Gender. Men develop CLL more often than women.

Race/Ethnicity. B-cell CLL is more common in people of Russian and European descent, and hardly ever develops in people from China, Japan, or Southeast Asian countries. It also occurs commonly in black people. The reason(s) for these differences is not known.

Agent Orange. The U.S. Department of Veterans Affairs lists CLL as a disease associated with exposure to Agent Orange, a chemical used during the Vietnam War.

To continue reading this guide, use the menu on the side of your screen to select another section.

Leukemia - Chronic Lymphocytic - CLL - Symptoms and Signs

This section has been reviewed and approved by the Cancer.Net Editorial Board, 07/2014

ON THIS PAGE: You will find out more about body changes and other things that can signal a problem that may need medical care. To see other pages, use the menu on the side of your screen.

People with CLL may experience the following symptoms or signs. Sometimes, people with CLL do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer.

Often, people have no symptoms and are diagnosed with CLL when the doctor finds many white blood cells during a blood test done for other reasons. Also, the immune system of people with CLL may not work well, and can sometimes make abnormal antibodies against their own red blood cells and/or platelets, destroying these cells and causing anemia or low numbers of platelets. These are called autoantibodies. This can happen at any time in people with CLL and is not necessarily related to the severity of their CLL. Other possible symptoms of CLL are:

  • Swelling of lymph nodes or glands in the neck, under the arms, or in the groin. This is a common symptom that people with CLL usually notice first.
  • Discomfort or fullness in the upper left part of the abdomen, caused when the spleen increases in size
  • Fever and infection
  • Abnormal bleeding
  • Shortness of breath
  • Weight loss
  • Fatigue
  • Chills
  • Night sweats
  • Feeling full despite not eating much
  • Rash
  • Malaise, or generally not feeling well

If you are concerned about one or more of the symptoms or signs on this list, please talk with your doctor. Your doctor will ask how long and how often you’ve been experiencing the symptom(s), in addition to other questions. This is to help find out the cause of the problem, called a diagnosis.

If leukemia is diagnosed, relieving symptoms remains an important part of care and treatment. This may also be called symptom management, palliative care, or supportive care. Be sure to talk with your health care team about symptoms you experience, including any new symptoms or a change in symptoms.

The next section helps explain what tests and scans may be needed to learn more about the cause of the symptoms. Use the menu on the side of your screen to select Diagnosis, or you can select another section, to continue reading this guide.

Leukemia - Chronic Lymphocytic - CLL - Diagnosis

This section has been reviewed and approved by the Cancer.Net Editorial Board, 07/2014

ON THIS PAGE: You will find a list of the common tests, procedures, and scans that doctors can use to find out what’s wrong and identify the cause of the problem. To see other pages, use the menu on the side of your screen.

Doctors use many tests to diagnose cancer and find out more about the disease. Some tests may also determine which treatments may be the most effective. This list describes options for diagnosing CLL, and not all tests listed will be used for every person. Your doctor may consider these factors when choosing a diagnostic test:

  • Age and medical condition
  • Type of cancer suspected
  • Signs and symptoms
  • Previous test results

The following tests may be used to diagnose CLL:

Blood tests. A routine blood test called a complete blood count (CBC) is the first test used to begin the process of diagnosing CLL. It is used to measure the number of different types of cells in a sample of a person’s blood. A person may have CLL if the blood contains too many white blood cells, called a high white blood cell count. The doctor will also use the blood test to find out which types of white blood cells are increased. The CBC can also measure if a patient has a low red blood cell count, known as anemia, and/or a low platelet count, known as thrombocytopenia.

Bone marrow aspiration and biopsy. CLL can usually be diagnosed with blood tests because the cancerous cells are easily found in the blood; therefore, a bone marrow aspiration and biopsy is not needed for most patients. These two procedures are similar and often done at the same time to examine the bone marrow before starting treatment. Bone marrow has both a solid and a liquid part. A bone marrow aspiration removes a sample of fluid with a needle. A bone marrow biopsy is the removal of a small amount of solid tissue using a needle. The sample(s) are then analyzed by a pathologist. A pathologist is a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease. A common site for a bone marrow aspiration and biopsy is the pelvic bone, which is located in the lower back by the hip. The skin in that area is usually numbed with medication beforehand, and other types of anesthesia (medication to block the awareness of pain) may be used.

For some patients, a bone marrow aspiration and biopsy may be used to help determine prognosis, which is the chance of recovery, or provide more information about the reasons that other blood counts may be abnormal. Although a bone marrow biopsy is usually not needed to diagnose CLL, it is often done before beginning treatment.

Flow cytometry and cytochemistry. In these tests, chemicals or dyes are applied to the cancer cells in the laboratory. These chemicals and dyes provide information about the leukemia and its subtype. CLL cells have distinctive markers, called cell surface proteins, on the outside of the cell. The pattern of these markers is called the immunophenotype. These tests are used to distinguish CLL from other kinds of leukemia, which can also involve lymphocytes. Both tests can be done from a blood sample. Flow cytometry, also called immunophenotyping, is the most important test to confirm a diagnosis of CLL.

Genomic and molecular testing:  Your doctor may recommend testing the leukemia cells for specific genes, proteins, chromosome changes, and other factors unique to the leukemia. Because CLL cells divide very slowly, looking at the chromosomes often is less useful than using tests to find specific genetic mutations or changes. Fluorescence in situ hybridization (FISH) assays detect a deletion of the long arm of chromosome 13 [del(13q)] in about half of patients. Other common abnormalities include an extra copy of chromosome 12 (trisomy 12), del(11q) or del(17p). More recently, other genetic tests, such as polymerase chain reaction, are used to identify smaller genetic changes that are not usually detected by FISH assays. Results of genetic and molecular testing can determine how quickly the disease will progress and will help decide whether your treatment options include a type of treatment called targeted therapy (see Treatment Options).

Imaging tests. CLL is generally found in many parts of the body, even if the disease has been diagnosed early. Imaging tests are rarely needed to diagnose CLL. They are sometimes used before treatment to find all parts of the body that are affected by CLL or to find out whether particular symptoms may be related to CLL. Imaging tests may also be used to see how well treatment is working.

  • An x-ray is a way to create a picture of the structures inside of the body, using a small amount of radiation. It may show if cancer is growing in lymph nodes in the chest.
  • A computed tomography (CT or CAT) scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows any abnormalities. It can detect lymph nodes with CLL around the heart, windpipe, lungs, abdomen, and pelvis. A CT scan can also be used to measure the size of the lymph nodes. Sometimes, a special dye called a contrast medium is given before the scan to provide better detail on the image. This dye can be injected into a patient’s vein or given as a liquid to swallow. CT scans can also help find out if CLL is in other organs, such as the spleen.
  • Positron emission tomography (PET) scans have not been proven to be helpful in diagnosing or staging CLL.

Your doctor may recommend additional tests before starting treatment to learn more about the leukemia and help plan treatment. After diagnostic tests are done, your doctor will review all of the results with you. If the diagnosis is leukemia, these results also help the doctor describe the disease; this is called staging.

The next section helps explain the different stages for CLL. Use the menu on the side of your screen to select Stages, or you can select another section, to continue reading this guide.

Leukemia - Chronic Lymphocytic - CLL - Stages

This section has been reviewed and approved by the Cancer.Net Editorial Board, 07/2014

ON THIS PAGE: You will learn about how doctors describe the growth or spread of CLL. This is called the stage. To see other pages, use the menu on the side of your screen.

Staging is a way of describing where the cancer is located, if or where it has spread, and whether it is affecting other parts of the body. Doctors use diagnostic tests to find out the cancer's stage, so staging may not be complete until all of the tests are finished. Knowing the stage helps the doctor to decide what kind of treatment is best and can help predict a patient's prognosis. There are different stage descriptions for different types of cancer.

There is a relationship between the stage of the CLL and the prognosis. In general, patients diagnosed at an earlier stage have better long-term survival. Importantly, however, there is a wide range of outcomes even for patients who have the same stage, and the stage alone cannot predict the prognosis with certainty for each person.

Below are explanations of commonly used staging and classification systems used by doctors to describe CLL:

Rai staging system (stage 0, I, II, III, or IV)

In this staging system, CLL is divided into five different stages, from 0 (zero) to IV (four). This staging system classifies the leukemia according to whether a patient has, or does not have, any of the following:

  • Lymphocytosis, which means there are high levels of lymphocytes
  • Lymphadenopathy, meaning a patient has enlarged lymph nodes
  • Splenomegaly, which is an enlarged spleen
  • Anemia, meaning low levels of red blood cells
  • Thrombocytopenia, meaning low levels of platelets
  • Hepatomegaly, which is an enlarged liver

This chart summarizes the Rai stages.

Rai Stage

High levels of lymphocytes

Enlarged lymph nodes

Enlarged spleen or liver


Low levels of platelets















Yes or no






Yes or no

Yes or no





Yes or no

Yes or no

Yes or no


Chart adapted from the American Society of Hematology, Kay et. al. 2002, vol. 1:193, Table 8.

Stage 0: The patient has lymphocytosis with more than 5000 lymphocytes per microliter of blood, but no other physical signs.

Stage I: The patient has lymphocytosis and enlarged lymph nodes. The patient does not have an enlarged liver or spleen, anemia, or low levels of platelets.

Stage II: The patient has lymphocytosis and an enlarged spleen and/or liver and may or may not have swollen lymph nodes.

Stage III: The patient has lymphocytosis and anemia. The patient may or may not have swollen lymph nodes and an enlarged liver or spleen.

Stage IV: The patient has lymphocytosis and low levels of platelets. The patient may or may not have swollen lymph nodes, an enlarged liver or spleen, or anemia.

If the CLL grows and worsens, the stage may change over time.

Risk group

Sometimes the phrase “risk group” is used to indicate the likelihood that the disease may worsen and require treatment.

Low risk: Rai stage 0

Intermediate risk: Rai stages I and II

High risk: Rai stages III and IV

Binet classification (stage A, B, or C)

European doctors use a different staging system, based on whether the CLL is found in the lymph nodes in the neck, under the arms, or in the groin area and whether the patient has low levels of red blood cells or platelets. The stages are called A, B, and C.

Binet stage

Number of enlarged lymph node areas


Low levels of platelets


Less than 3




3 or more




Any number

Yes (or low platelets)

Yes (or anemia)

Chart adapted from the American Society of Hematology, Kay et. al.2002, vol. 1:193, Table 8.

Stage A: The patient does not have anemia or low levels of platelets. The cancer can be felt in fewer than three areas of lymph nodes (Rai stages 0, I and II).

Stage B: The patient does not have anemia or low levels of platelets. The cancer is in three or more areas of lymph nodes (Rai stages I and II).

Stage C: The patient has anemia and/or low levels of platelets. The cancer is in any number of lymph nodes (Rai stages III and IV).

Information about the stage of CLL will help the doctor recommend a treatment plan.  The next section helps explain the treatment options for CLL. Use the menu on the side of your screen to select Treatment Options, or you can select another section, to continue reading this guide.

Leukemia - Chronic Lymphocytic - CLL - Treatment Options

This section has been reviewed and approved by the Cancer.Net Editorial Board, 07/2014

ON THIS PAGE: You will learn about the different ways doctors use to treat people with CLL. To see other pages, use the menu on the side of your screen.

This section outlines treatments that are the standard of care (the best proven treatments available) for this specific type of leukemia. When making treatment plan decisions, patients are also strongly encouraged to consider clinical trials as an option. A clinical trial is a research study to test a new approach to treatment to evaluate whether it is safe, effective, and possibly better than the standard treatment. Clinical trials may test such approaches as a new drug, a new combination of standard treatments, or new doses of current therapies. Your doctor can help you review all treatment options. For more information, see the Clinical Trials and Latest Research sections.

Treatment overview

In cancer care, different types of doctors often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team.

Treatment options and recommendations depend on several factors, including the type and stage of leukemia, possible side effects, and the patient’s preferences, age, and overall health. Your care plan may also include treatment for symptoms and side effects, an important part of cancer care. Because CLL often develops slowly, many people may not need treatment right away, and some may never need treatment at all. Although the current standard treatments can be highly effective, it is uncertain whether any treatment can completely get rid of CLL, and most patients are not cured of the disease with treatment. The goal of treatment is to ease symptoms and produce a long-term remission (see below).

Descriptions of the most common treatment options for CLL are listed below. Take time to learn about all of your treatment options and be sure to ask questions about things that are unclear. Also, talk about the goals of each treatment with your doctor and what you can expect while receiving the treatment. Learn more about making treatment decisions.

Watch and wait/active surveillance for early-stage CLL

Patients with symptoms and/or large amounts of CLL in the blood, lymph nodes, or spleen need treatment shortly after the diagnosis is made. For other patients, however, immediate treatment is not needed, and it is recommended that the disease is monitored carefully without active treatment. During this time, the patient’s blood counts are watched closely and physical examinations are performed on a regular basis. If the CLL shows signs of worsening, active treatment would then begin. Research studies have shown that no harm comes from the watch-and-wait approach, also called active surveillance or watchful waiting, when compared with immediate treatment for early-stage CLL. Some patients do not develop symptoms for years, or even decades, and will not need any treatment.

Although many patients can live comfortably with CLL without active treatment, it is beneficial to use this time to improve overall health. This includes stopping smoking and bringing all immunizations up to date. However, patients with CLL should not receive the herpes zoster (shingles) vaccine because it may cause a shingles infection in patients who have a lowered immune system.

Treatment is recommended for patients with worsening blood counts and for those who develop symptoms. These might include increased fatigue, night sweats, enlarged lymph nodes, or lowered red blood cell or platelet counts. People with CLL are encouraged to talk with their doctor about whether their symptoms need treatment, balancing the benefits of treatment with the side effects.


Chemotherapy is the use of drugs to destroy cancer cells, usually by stopping the cancer cells’ ability to grow and divide. Chemotherapy is given by a medical oncologist, a doctor who specializes in treating cancer with medication, or a hematologist, a doctor who specializes in treating blood disorders.

Systemic chemotherapy is delivered by mouth or through the bloodstream to reach cancer cells throughout the body. Common ways to give chemotherapy include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally). Chemotherapy may also be given as an injection under the skin, called a subcutaneous injection. A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a set period of time. Sometimes, a doctor may use a combination of drugs, but a combination of drugs is not always better than a single drug. When treatment begins, doctors may use a number of different drugs depending on the stage of the disease and the person’s age and health.

A standard drug that people with CLL may receive is called fludarabine (Fludara). Similar drugs called pentostatin (Nipent) and cladribine (Leustatin) are also sometimes used to treat CLL, although fludarabine is used most commonly.

Chlorambucil (Leukeran) and cyclophosphamide (Neosar) can be given orally, while cyclophosphamide can also be given intravenously. Cyclophosphamide may be given alone or with fludarabine or with prednisone (multiple brand names), a type of oral corticosteroid.

In the past, patients initially received either fludarabine only or chlorambucil plus prednisone, switching to the other regimen if the treatment did not work well, but more recent combinations are now recommended for initial therapy. Today, the following drugs are often given together in combinations:

  • Rituximab (Rituxan) (see monoclonal antibodies below) and fludarabine (sometimes abbreviated as FR)
  • Cyclophosphamide and fludarabine (called FC)
  • Cyclophosphamide, fludarabine and rituximab (called FCR)
  • Pentostatin, cyclophosphamide, and rituximab (called PCR)
  • Bendamustine (Treanda) and rituximab (called BR)

The choice of treatment often depends on the patient’s age, general health, and the interest in and availability of clinical trials. Clinical trials evaluating other experimental drugs, including alvocidib (flavopiridol), lenalidomide (Revlimid), and ABT-199 are described in Latest Research.

Learn more about chemotherapy and preparing for treatment. The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. Learn more about your prescriptions by using searchable drug databases.

Targeted therapy

Targeted therapy is a treatment that targets the leukemia’s specific genes, proteins, or the tissue environment that contributes to its growth and survival. This type of treatment blocks the growth and spread of leukemia cells while limiting damage to healthy cells.

Recent studies show that not all cancers have the same targets. To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors in your leukemia. As a result, doctors can better match each patient with the most effective treatment whenever possible. In addition, many research studies are taking place now to find out more about specific molecular targets and new treatments directed at them. Learn more about targeted treatments.

Monoclonal antibodies. A monoclonal antibody is a type of targeted therapy. It is directed against a specific protein in the surface of leukemia cells, and it does not affect cells that do not have that protein.

Rituximab is a monoclonal antibody given intravenously, that binds to a protein on the surface of B cells, destroying some of the CLL cells and also making chemotherapy more effective. As mentioned above, rituximab is currently being used in combination with chemotherapy.

Alemtuzumab (Campath) is another monoclonal antibody that has been approved by the U.S. Food and Drug Administration (FDA) as a treatment for advanced CLL when other treatments no longer work. It can be used for both T-cell and B-cell CLL. This antibody can be given either intravenously or as an injection under the skin. Similarly, two new antibodies called ofatumumab (Arzerra) and obinituzumab (Gazyva) have recently been approved for the treatment of CLL.

Kinase inhibitors. Ibrutinib (Imbruvica) is a drug called a kinase inhibitor that is given orally which targets Bruton’s tyrosine kinase, an important factor influencing the growth of B cells. Kinases are enzymes found in both normal cells and cancer cells. Some cancer cells can be destroyed by drugs that block this particular kinase enzyme. Ibrutinib is approved by the FDA for patients with CLL who have already received at least one other treatment.

Idelalisib (Zydelig) is another type of kinase inhibitor. It is approved by the FDA in combination with rituximab for patients with CLL that comes back after treatment when rituximab alone would be considered appropriate therapy; see more below.

Side effects from chemotherapy and targeted therapy

Chemotherapy and targeted therapy cause side effects. It is important to talk with your doctor about possible side effects for a specific medication and how they can be managed. The side effects of the common medications used to treat CLL are discussed below.

Chemotherapy for CLL may cause hair loss and nausea and vomiting, although nausea and vomiting can often be prevented with drugs. Doctors will also closely watch for decreases in normal blood counts, which can increase a person’s risk of infection, bleeding, and fatigue. To manage these side effects, some patients need transfusions of red blood cells and platelets or antibiotics to treat infections.

Decreases in blood counts after chemotherapy are sometimes more severe for people with CLL than for people with other types of cancer because of the CLL cells in the bone marrow. Patients should talk with their doctors about the symptoms they might experience, how they could be prevented, and how closely they should be monitored. 

Sometimes, subcutaneous injections of white blood cell growth factors such as filgrastim (Neupogen), sargramostim (Leukine), or pegfilgrastim (Neulasta) are used to help the bone marrow make normal white blood cells. Injections of epoetin (Epogen, Eprex, Procrit) or darbepoetin (Aranesp) may be given to treat anemia caused by chemotherapy. However, these drugs also have risks, and it is important for you and your doctor to carefully consider the risks and the benefits. Read more about ASCO’s recommendations for when white blood cell growth factors and epoetin and darbepoetin treatment should be used.

Often, a person’s first treatments with rituximab, alemtuzumab, obinituzumab, or ofatumumab cause fevers and chills, which usually go away after the first few treatments. 

One of the side effects of both CLL and its treatment is the risk of developing a bacterial, viral, or fungal infection. Doctors may call these opportunistic infections. In particular, patients with CLL often develop infections with herpes viruses, either as cold sores or as shingles. Shingles can become quite painful and turn into a severe infection. Patients should tell their doctors right away if they notice a rash or skin problems that look like blisters and are grouped together in a band across the chest or abdomen, or down one leg or arm, or on the face. These infections can be treated with antiviral drugs, and treatment works better when started sooner.

Radiation therapy
Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. A radiation therapy regimen usually consists of a specific number of treatments given over a set period of time. Radiation therapy is not often used to treat CLL because the disease is located throughout the body. However, radiation therapy can be very helpful to shrink an enlarged spleen or swollen lymph nodes and relieve symptoms.

Side effects from radiation therapy may include fatigue, mild skin reactions, upset stomach, and loose bowel movements. Most side effects go away soon after treatment is finished. Learn more about radiation therapy.


Occasionally, surgery to remove the spleen, called a splenectomy may be recommended because the spleen can become very enlarged in CLL. A surgical oncologist is a doctor who specializes in treating cancer using surgery. Learn more about surgery.

Getting care for symptoms and side effects

Leukemia and its treatment often cause side effects. In addition to treatment to slow, stop, or eliminate the disease, an important part of care is relieving a person’s symptoms and side effects. This approach is called palliative or supportive care, and it includes supporting the patient with his or her physical, emotional, and social needs.

Supportive care can help a person at any stage of illness. People often receive treatment for the leukemia and treatment to ease side effects at the same time. In fact, patients who receive both often have less severe symptoms, better quality of life, and report they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, and other therapies. You may also receive palliative treatments similar to those meant to eliminate the CLL, such as chemotherapy, surgery, and radiation therapy. Talk with your doctor about the goals of each treatment in your treatment plan.

Before treatment begins, talk with your health care team about the possible side effects of your specific treatment plan and supportive care options. And during and after treatment, be sure to tell your doctor or another health care team member if you are experiencing a problem so it is addressed as quickly as possible. Learn more about palliative care.

Refractory CLL

If the leukemia has not responded to treatment, the disease is called refractory CLL. Patients with this diagnosis are encouraged to talk with doctors who are experienced in treating this stage of leukemia, because there can be different opinions about the best treatment plan. Learn more about seeking a second opinion before starting treatment, so you are comfortable with the treatment plan chosen. This discussion may include clinical trials. Supportive care will also be important to help relieve symptoms and side effects.

If CLL becomes resistant to one drug, meaning that the drug no longer works, treatment with other types of drugs is often recommended. Some symptoms of CLL can be treated in other ways, such as with radiation therapy or rarely, a splenectomy. Some patients who have infections that keep coming back may benefit from immunoglobulin given by IV each month because patients with CLL have fewer normal antibodies. Patients who make antibodies that destroy their own red blood cells and/or platelets (see Symptoms) often need high doses of corticosteroids to stop the body from making these antibodies. Sometimes, treatment with rituximab or a splenectomy can be helpful for these patients.

Stem cell transplantation/bone marrow transplantation. A stem cell transplant is a medical procedure in which bone marrow that contains leukemia is replaced by highly specialized cells, called hematopoietic stem cells, that develop into healthy bone marrow. Hematopoietic stem cells are blood-forming cells found both in the bloodstream and in the bone marrow. Today, this procedure is more commonly called a stem cell transplant, rather than bone marrow transplant, because it is the stem cells in the blood that are typically being transplanted, not the actual bone marrow tissue.

There are two types of stem cell transplantation depending on the source of the replacement blood stem cells: allogeneic (ALLO) and autologous (AUTO). ALLO uses donated stem cells, while AUTO used the patient’s own stem cells. ALLO is the type of transplant used for treating CLL and is typically considered for younger patients either when the standard treatments have not worked well or the patient has a high risk of the CLL returning more quickly. The goal is to destroy all of the cancer cells in the marrow, blood, and other parts of the body using high doses of chemotherapy and/or radiation therapy and then allow replacement blood stem cells to create healthy bone marrow. Learn more about stem cell and bone marrow transplantation.

For most patients, a diagnosis of refractory CLL is very stressful and, at times, difficult to bear. Patients and their families are encouraged to talk about the way they are feeling with doctors, nurses, social workers, or other members of the health care team. It may also be helpful to talk with other patients, including through a support group.


The goal of treatment is to relieve any symptoms from CLL and to reduce the amount of remaining CLL as much as possible. A complete remission (CR) occurs when the doctor cannot find any evidence of leukemia remaining after repeated testing. A partial remission (PR) is when there is some leukemia remaining. A PR is most common for people with CLL who receive the current standard treatments. With a PR, patients can feel quite well with normal blood counts, have no swollen lymph nodes or spleen, but still have detectable amounts of CLL in the bone marrow.

The goal of newer, more intensive treatments or targeted therapies is to destroy more cancer cells in the hope of lengthening a person’s life. In the future, the definition of a CR in CLL is likely to change with advances in technology. For example, some sensitive tests can find very small levels of the abnormal DNA changes specific to CLL. When these sensitive tests can no longer find any CLL, it is called a molecular remission.

The chance of recurrence

A remission can be temporary or permanent. This uncertainty leads to many survivors feeling worried or anxious that the leukemia will come back. Recurrent CLL is CLL that has come back after treatment. While many remissions last for a long time, it is important to talk with your doctor about the possibility of the disease returning. Understanding the risk of recurrence and the treatment options may help you feel more prepared if the leukemia does return. Learn more about coping with the fear of recurrence.

When this occurs, a cycle of testing will begin again to learn as much as possible about the recurrence, including whether the leukemia’s stage has changed. After testing is done, you and your doctor will talk about your treatment options. Often the treatment plan will include the therapies described above such as chemotherapy and targeted therapy, but they may be used in a different combination or given at a different pace. Your doctor may also suggest clinical trials that are studying new ways to treat this type of recurrent leukemia.

Finding a CLL recurrence does not mean that treatment is needed right away. In fact, the watch-and-wait approach (see above) is usually recommended, with active treatment beginning only if the disease causes symptoms again.

People with recurrent leukemia often experience emotions such as disbelief or fear. Patients are encouraged to talk with their health care team about these feelings and ask about support services to help them cope. Learn more about dealing with cancer recurrence.

If treatment fails

Recovery from leukemia is not always possible. If treatment is not successful, the disease may be called advanced or terminal leukemia.

This diagnosis is stressful, and it may be difficult to discuss. However, it is important to have open and honest conversations with your doctor and health care team to express your feelings, preferences, and concerns. The health care team is there to help, and many team members have special skills, experience, and knowledge to support patients and their families. Making sure a person is physically comfortable and free from pain is extremely important.

Patients who have advanced disease and who are expected to live less than six months may want to consider a type of palliative care called hospice care. Hospice care is designed to provide the best possible quality of life for people who are near the end of life. You and your family are encouraged to think about where you would be most comfortable: at home, in the hospital, or in a hospice environment. Nursing care and special equipment can make staying at home a workable alternative for many families. Learn more about advanced cancer care planning.

After the death of a loved one, many people need support to help them cope with the loss. Learn more about grief and loss.

The next section helps explain clinical trials, which are research studies. Use the menu on the side of your screen to select About Clinical Trials, or you can select another section, to continue reading this guide.

Leukemia - Chronic Lymphocytic - CLL - About Clinical Trials

This section has been reviewed and approved by the Cancer.Net Editorial Board, 07/2014

ON THIS PAGE: You will learn more about clinical trials, which are the main way that new medical approaches are tested to see how well they work. To see other pages, use the menu on the side of your screen.

Doctors and scientists are always looking for better ways to treat patients with CLL. To make scientific advances, doctors create research studies involving volunteers, called clinical trials.

Many clinical trials are focused on new treatments, evaluating whether a new treatment is safe, effective, and possibly better than the current (standard) treatment. These types of studies evaluate new drugs, different combinations of existing treatments, new approaches to radiation therapy or surgery, and new methods of treatment. Patients who participate in clinical trials are often among the first to receive new treatments, such as new chemotherapy, before they are widely available. However, there is no guarantee that the new treatment will be safe, effective, or better than a standard treatment.

There are also clinical trials that study new ways to ease symptoms and side effects during treatment and manage the late effects that may occur after treatment. Talk with your doctor about clinical trials regarding side effects. In addition, there are ongoing studies about ways to prevent the disease.

Patients decide to participate in clinical trials for many reasons. For some patients, a clinical trial is the best treatment option available. Because standard treatments are not perfect, patients are often willing to face the added uncertainty of a clinical trial in the hope of a better result. Other patients volunteer for clinical trials because they know that these studies are the only way to make progress in treating CLL. Even if they do not benefit directly from the clinical trial, their participation may benefit future patients with CLL.

Sometimes people have concerns that, by participating in a clinical trial, they may receive no treatment by being given a placebo or a “sugar pill.” The use of placebos in cancer clinical trials is rare. When a placebo is used in a study, it is done with the full knowledge of the participants. Find out more about placebos in cancer clinical trials.

To join a clinical trial, patients must participate in a process known as informed consent. During informed consent, the doctor should list all of the patient’s options, so that the person understands how the new treatment differs from the standard treatment. The doctor must also list all of the risks of the new treatment, which may or may not be different from the risks of standard treatment. Finally, the doctor must explain what will be required of each patient in order to participate in the clinical trial, including the number of doctor visits, tests, and the schedule of treatment.

For specific topics being studied for CLL, learn more in the Latest Research section.

Patients who participate in a clinical trial may stop participating at any time for any personal or medical reason. This may include that the new treatment is not working or there are serious side effects. Clinical trials are also closely monitored by experts who watch for any problems with each study. It is important that patients participating in a clinical trial talk with their doctor and researchers about who will be providing their treatment and care during the clinical trial, after the clinical trial ends, and/or if the patient chooses to leave the clinical trial before it ends. 

Cancer.Net offers a lot of information about cancer clinical trials in other areas of the website, including a complete section on clinical trials and places to search for clinical trials for a specific type of cancer.

The next section helps explain the areas of research going on today about CLL. Use the menu on the side of your screen to select Latest Research, or you can select another section, to continue reading this guide.

Leukemia - Chronic Lymphocytic - CLL - Latest Research

This section has been reviewed and approved by the Cancer.Net Editorial Board, 07/2014

ON THIS PAGE: You will read about the scientific research being done now to learn more about CLL and how to treat it. To see other pages, use the menu on the side of your screen.

Doctors are working to learn more about CLL, ways to prevent it, how to best treat it, and how to provide the best care to people diagnosed with this disease. The following areas of research may include new options for patients through clinical trials. Most cancer centers are focused on clinical trials aimed at increasing the number of patients who have a complete remission. Always talk with your doctor about the diagnostic and treatment options best for you.

New drugs and drug combinations. Researchers are working to find new drugs for CLL. Different combinations of chemotherapy and targeted therapy are also being studied as a way to increase the likelihood that a patient will have a complete remission and live longer. There are many new drugs for CLL being evaluated in clinical trials for patients with recurrent CLL with the hope of testing some of these drugs as initial therapy in the near future. 

  • Researchers are also looking at combining ibrutinib with bendamustine and ofatumumab.
  • Idelalisib is being studied in combination with bendamustine, rituximab, and ofatumumab.
  • Flavopiridol is a drug given intravenously that is being studied as a treatment for CLL when few standard treatments have helped control the disease.
  • Xm5574 is a monoclonal antibody also being researched for treatment of CLL.
  • Lenalidomide is drug commonly used to treat multiple myeloma that is also being looked at as a treatment for CLL, either by itself or in combination with several different drugs for patients with recurrent or refractory CLL, as well as for those who have not yet received treatment.
  • ABT199 is a drug that can destroy CLL cells by blocking an enzyme called BCL-2

Stem cell/bone marrow transplantation. Researchers are looking at decreasing the side effects of stem cell transplantation by using reduced intensity transplantation, which uses much lower doses of chemotherapy, making it possible for some older patients to receive stem cell transplantation. Also being studied in clinical trials are different approaches to ALLO transplantation for patients with CLL when chemotherapy is not working well.

Genetics. Genetic changes specific to CLL cells are also being evaluated to help predict how well treatment will work, determine the best treatment, and provide information about the cause of the disease. Examples include measuring the immunoglobulin mutations of the CLL cells, finding different chromosomal abnormalities in the CLL cells, and studying the effects of a protein called ZAP-70, which is found on the surface of the CLL cells. Some research suggests that these markers can predict the likelihood that the disease may worsen faster. However, there is often a large difference in how well treatment works for patients who seem to have the same genetic markers, and it is too early to use these tests to make decisions about when to begin treatment and the type of treatment to use.

Supportive care. Clinical trials are underway to find better ways of reducing symptoms and side effects of current CLL treatments in order to improve patients’ comfort and quality of life.

Looking for More About the Latest Research?

If you would like additional information about the latest areas of research regarding CLL, explore these related items that take you outside of this guide:

  • To find clinical trials specific to your diagnosis, talk with your doctor or search online clinical trial databases now.
  • Review research announced at the 2014 and 2013 ASCO Annual Meetings. 
  • Visit ASCO’s CancerProgress.Net website to learn more about the historical pace of research for leukemia. Please not that this link takes you to a separate ASCO website.

The next section addresses how to cope with the symptoms of the disease or the side effects of its treatment. Use the menu on the side of your screen to select Coping with Side Effects, or you can select another section, to continue reading this guide.

Leukemia - Chronic Lymphocytic - CLL - Coping with Side Effects

This section has been reviewed and approved by the Cancer.Net Editorial Board, 07/2014

ON THIS PAGE: You will find out more about steps to take to help cope with physical, social, and emotional side effects. This page includes several links outside of this guide to other sections of this website. To see other pages, use the menu on the side of your screen.

Fear of treatment side effects is common after a diagnosis of leukemia, but it may help to know that preventing and controlling side effects is a major focus of your health care team. This is called palliative or supportive care, and it is an important part of the overall treatment plan, regardless of the stage of disease.

Common side effects from each treatment option for CLL are described in detail within the Treatment Options section. Learn more about the most common side effects of cancer and different treatments, along with ways to prevent or control them. Side effects depend on a variety of factors, including the stage, the length and dosage of treatment(s), and your overall health.

Before treatment begins, talk with your doctor about possible side effects of each type of treatment you will be receiving. Ask which side effects are most likely to happen, when they are likely to occur, and what can be done to prevent or relieve them. And, ask about the level of caregiving you may need during treatment and recovery, as family members and friends often play an important role in the care of a person with CLL. Learn more about caregiving.

In addition to physical side effects, there may be emotional and social effects as well. Patients and their families are encouraged to share their feelings with a member of their health care team who can help with coping strategies, including concerns about managing the cost of your cancer care

During and after treatment, be sure to tell the health care team about the side effects you experience, even if you feel they are not serious. Sometimes, side effects can last beyond the treatment period, called a long-term side effect. A side effect that occurs months or years after treatment is called a late effect. Treatment of both types of effects is an important part of survivorship care. Learn more by reading the After Treatment section or talking with your doctor.

The next section helps explain medical tests and check-ups needed after finishing treatment for CLL. Use the menu on the side of your screen to select After Treatment, or you can select another section, to continue reading this guide.

Leukemia - Chronic Lymphocytic - CLL - After Treatment

This section has been reviewed and approved by the Cancer.Net Editorial Board, 07/2014

ON THIS PAGE: You will read about your medical care after treatment is finished and why this follow-up care is important. To see other pages, use the menu on the side of your screen.

After treatment for CLL ends, talk with your doctor about developing a follow-up care plan. This plan may include regular physical examinations and/or medical tests to monitor your recovery for the coming months and years. ASCO offers cancer treatment summary forms to help keep track of the cancer treatment you received and develop a survivorship care plan once treatment is completed.

People should receive regular follow-up examinations for several years to watch for any signs of recurrence or late effects, which are side effects that occur years after treatment. People with CLL also have a higher risk of developing other cancers, particularly lung, colon, or skin cancers, and they should tell their doctors if they notice new symptoms or worsening skin problems or moles. The chemotherapy drugs used to treat CLL may damage the DNA in normal bone marrow cells and cause a different type of leukemia several years later; this is called therapy-related myeloid leukemia.

People recovering from CLL are encouraged to follow established guidelines for good health, such as maintaining a healthy weight, not smoking, eating a balanced diet, bringing immunizations up to date, especially the annual flu shot and periodic pneumonia vaccines, and having recommended cancer screening tests. Talk with your doctor to develop a plan that is best for your needs. Moderate physical activity can help rebuild your strength and energy level. Your doctor can help you create an appropriate exercise plan based upon your needs, physical abilities, and fitness level. Learn more about the next steps to take in survivorship, including making positive lifestyle changes.

The next section offers a list of questions you may want to ask. Use the menu on the side of your screen to select Questions to Ask the Doctor, or you can select another section, to continue reading this guide.

Leukemia - Chronic Lymphocytic - CLL - Questions to Ask the Doctor

This section has been reviewed and approved by the Cancer.Net Editorial Board, 07/2014

ON THIS PAGE: You will find some questions to ask your doctor or other members of your health care team, to help you better understand your diagnosis, treatment plan, and overall care. To see other pages, use the menu on the side of your screen.

Talking often with the doctor is important to make informed decisions about your health care. These suggested questions are a starting point to help you learn more about your care and treatment. You are also encouraged to ask additional questions that are important to you. You may want to print this list and bring it to your next appointment, or download Cancer.Net’s free mobile app for an e-list and other interactive tools to help manage your care.

  • What is my diagnosis?
  • Can you explain my pathology report (laboratory test results) to me?
  • What stage or risk group is the CLL? What does this mean?
  • How often do you treat people with CLL?
  • Where is the best place for me to be treated?
  • What are my options for treatment?
  • What is the goal of each treatment option?
  • What clinical trials are open to me? Where are they located, and how do I find out more about them?
  • What treatment plan do you recommend? Why?
  • If a clinical trial is recommended, will I receive treatment nearby or will I need to travel to the treatment center?
  • What is the goal of each treatment? Is it to eliminate the leukemia, help me feel better, or both?
  • Who will be part of my health care team, and what does each member do?
  • Who will be coordinating my overall treatment and follow-up care?
  • Do I need to start treatment right away? If not, please explain why treatment does not need to begin as soon as possible.
  • What are the possible side effects of this treatment, both in the short term and long term?
  • How will this treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?
  • Could this treatment affect my sex life? If so, how and for how long?
  • Could this treatment affect my ability to become pregnant or have children? If so, should I talk with a fertility specialist before cancer treatment begins?
  • If I’m worried about managing the costs related to my cancer care, who can help me with these concerns?
  • What follow-up tests will I need, and how often will I need them?
  • What support services are available to me? To my family?
  • Whom should I call for questions or problems?

The next section offers some more resources that may be helpful to you. Use the menu on the side of your screen to select Additional Resources, or you can select another section, to continue reading this guide.

Leukemia - Chronic Lymphocytic - CLL - Additional Resources

This section has been reviewed and approved by the Cancer.Net Editorial Board, 07/2014

ON THIS PAGE: You will find some helpful links to other areas of Cancer.Net that provide information about cancer care and treatment. This is the final page of Cancer.Net’s Guide to Chronic Lymphocytic Leukemia. To go back and review other pages, use the menu on the side of your screen.

Cancer.Net includes many other sections about the medical and emotional aspects of cancer, both for the person diagnosed and their family members and friends. This website is meant to be a resource for you and your loved ones from the time of diagnosis, through treatment, and beyond. Here are a few sections that may get you started in exploring the rest of Cancer.Net:

- Search for a leukemia specialist in your local area using this free database of doctors from the American Society of Clinical Oncology.

- Review dictionary articles to help understand medical phrases and terms used in leukemia care and treatment.

- Read more about the first steps to take when newly diagnosed with leukemia.

- Find out more about clinical trials as a treatment option.

- Learn more about coping with the emotions that leukemia can bring, including those within a family or a relationship.

- Find a national, not-for-profit advocacy organization that may offer additional information, services, and support for people with this type of leukemia.

- Explore next steps a person can take after active treatment is complete.

This is the end of the Cancer.Net’s Guide to Chronic Lymphocytic Leukemia. Use the menu on the side of your screen to select another section to continue reading this guide.