Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia among adults. If you have CLL, your bone marrow is producing abnormal white blood cells called lymphocytes. Healthy lymphocytes help the body fight infection, but in CLL, abnormal lymphocytes may outnumber their healthy counterparts.

Chronic lymphocytic leukemia is a slow-growing disease. Symptoms, such as fatigue and swollen lymph nodes, usually don’t occur until the later stages. Cancer specialists use blood tests to diagnose CLL. Using treatments such as chemotherapy, radiation therapy, and targeted therapy, oncologic hematologists are able to slow the growth of abnormal cells and send the disease into remission. 

When Bad Blood Cells Push Out the Good

All of your blood cells, including lymphocytes, start out in the bone marrow as blood stem cells. 

When CLL has developed, the blood stem cells mature and become abnormal lymphocytes, or leukemia cells. These cells don’t have the infection-fighting ability of healthy lymphocytes – and they take up more and more room in the blood and bone marrow, leaving little space for healthy blood cells. Eventually, leukemia cells may spread beyond the blood to organs. These cells can also affect the lymph nodes.

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Lymphocytic Leukemia

Who is at Risk for Developing Chronic Lymphocytic Leukemia

Mutations in the genes of bone marrow cells cause chronic lymphocytic leukemia, but it’s unclear why these genetic changes occur. Rarely, individuals may inherit genetic mutations from a parent that increase their risk for CLL. However, in most cases of CLL, these changes develop on their own.

Experts have identified several factors that may raise your chronic lymphocytic leukemia risk, including:

  • Being older than 50
  • Being male
  • Being white
  • Exposure to certain chemicals, including radon and Agent Orange, a plant-killing chemical used in the Vietnam War
  • Having a parent, sibling, or child with chronic lymphocytic leukemia

If you have CLL risk factors, you won’t necessarily develop the disease. On the other hand, the absence of risk factors doesn’t mean CLL won’t occur – some cases develop without known risk factors. 

Chronic Lymphocytic Leukemia Symptoms

Early on, chronic lymphocytic leukemia often develops silently, without symptoms. However, if the disease progresses, symptoms may appear. Signs to watch for include:

  • Swollen lymph nodes, which appear as lumps in certain areas of the body, such as the neck, underarms, and groin. These are usually not painful.
  • Feeling of fullness below the ribs, which may be due to an enlarged spleen or liver
  • Fever
  • Night sweats
  • Fatigue
  • Unexplained weight loss

Diagnosing Chronic Lymphocytic Leukemia

It’s often an abnormal blood test result, not symptoms, that lead to a CLL diagnosis according to the Leukemia & Lymphoma Society. For example, your physician might notice a higher-than-normal white blood cell count from a blood sample taken during your annual physical exam. Further investigation might reveal CLL as the cause. 

Most patients who have an abnormal blood test result without an obvious reason are seen by a hematologist. This doctor specializes in blood diseases, including blood cancers such as leukemia. 

The hematologist is likely to order a complete blood count test. This will give an indication as to whether a high number of lymphocytes are present which could mean CLL.

Flow cytometry tests are likely to be done if the lymphocyte count is high. This tells the hematologist more about the reason for the high count and if CLL is present, it will give an indication of whether it’s aggressive or slower-growing.

If you’re diagnosed with chronic lymphocytic leukemia, another important step is to determine whether the disease has spread to the organs or lymph nodes. This is known as staging the cancer, and it helps your hematologist decide how to approach treatment.

Genetic tests may be run to look for gene mutations associated with chronic lymphocytic leukemia. The results of these tests can impact the types of treatments that are likely to work best. 

A PET-CT scan helps the hematologist determine if there are areas where the cancer has spread but can’t be seen with the naked eye.

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Rai Staging System

In this staging system, CLL is divided into 5 different stages, from 0 (zero) to IV (4). 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 in the blood
  • 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

Staging Groups

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.


Chronic Lymphocytic Leukemia Treatments

Your cancer specialists will consider many factors when deciding how to treat chronic lymphocytic leukemia. These include your overall health, the stage of the disease, whether you’re experiencing symptoms, how quickly the cancer is progressing, and blood cell levels. 

If Your CLL is Slow-Growing

If you don’t have symptoms, your team may recommend watchful waiting. In other words, you’ll receive close monitoring for any signs that the disease is progressing.

If you need active treatment, the first line of treatment usually includes a combination of a few different treatments. The right combination for each patient is based on the test results. If the first-line treatment isn’t effective, there are some other drug combinations that can be used. The drugs are divided into a few different categories:



Medication that travels through the blood to kill or impede the spread of cancer cells. The majority of patients can take oral chemotherapy as a part of their treatment regimens, instead of just IV-based drugs. If your tests showed high numbers of lymphocytes a process called leukapheresis may be needed to remove some of the abnormal lymphocytes before chemo begins. This allows for less chemo to be needed for it to be effective.


Monoclonal Antibodies

This type of drug can be referred to as a targeted therapy or an immunotherapy. That's because some of the monoclonal antibodies used to treat CLL have a specific target on a cancer cell that they aim to find, attach to, and attack. Other types of monoclonal antibodies help the immune system respond better to allow the body to find and attack cancer cells more effectively.


Other Immunotherapies and Targeted Therapies

These drugs may be selected in addition to or instead of monoclonal antibodies based on the specific genetic makeup of the cancer cells. There is extensive research under way for CAR-T immunotherapy treatments for leukemia patients.


Radiation Therapy

Radiation therapy for CLL is less common because there isn’t necessarily a single point where the radiation can be aimed. That’s because blood cancers run throughout the entire body. However, it can help reduce pain from swollen organs or enlarged lymph nodes.

If you have a type of chronic lymphocytic leukemia that is hard to treat or returns after treatment, you may need a stem cell transplant. The stem cells can come from your blood or bone marrow, or from a donor. A stem cell transplant can help replace bone marrow and blood cells lost to high-dose chemotherapy.

The team at Rocky Mountain Cancer Centers includes hematologists who specialize in CLL. They will help you evaluate when to start treatments since it’s often a slow-growing type of blood cancer. And, when the time comes for treatment, they will run the tests to determine which combinations are likely to work best for you. Clinical research is also available through RMCC which means the most recent treatment options may be available to you. Talk to your RMCC specialist about whether there is a trial that you qualify for.

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Watch Now

Learn more about CLL from medical oncologist/hematologist Dr. Paul “Tony” DeCarolis.