Have you heard of Chronic Lymphocytic Leukemia (CLL)? Let's talk about it in detail!

Do you sometimes just feel very tired? Or do you often get a fever? Do you have small lumps that feel like they're on your neck, armpits, or groin? These could be signs of Chronic Lymphocytic Leukemia, or CLL for short. But don't worry, because having all these symptoms doesn't mean you have this disease. But it's very important to be aware of things like this. So let's talk about CLL in a simple way today, okay?

What is chronic lymphocytic leukemia (CLL)? Simply put...

Chronic lymphocytic leukemia (CLL) is a type of blood cancer . It is the most common type of leukemia in adults. Blood cells are produced in the bone marrow. This condition occurs when lymphocytes, a type of healthy white blood cell in the bone marrow, become abnormal, meaning they change and become cancerous. These cancerous cells multiply uncontrollably, crowding out healthy blood cells and platelets, which help blood clot.

CLL most often occurs in people over the age of 65. However, it can sometimes occur in people as young as 30. What's more, some people can have CLL without any symptoms . Many people find out about the condition when they have a blood test for another condition or during a routine annual medical checkup.

Currently, there is no cure for CLL. But that is not a cause for concern. Over the past decade, doctors have developed new treatments that can control CLL and put it into remission . These treatments have allowed people with CLL to live much longer.

What are the main types of CLL?

There are two main types of white blood cells in our bodies, called lymphocytes. CLL can develop in only one of these two types.

• B-lymphocytes (B-cells): These are the cells that produce antibodies, a type of protein that recognizes and fights harmful germs, bacteria, viruses, and even cancer cells.
• T-lymphocytes (T-cells): These control our body's immune system responses. They also find and directly destroy abnormal cells, such as cancer cells.

The most common type of CLL is B-cell CLL . There is a related condition that affects T-cells, called T-cell prolymphocytic leukemia (PLL). However, people with PLL develop symptoms more quickly than people with B- cell CLL.

How common is this condition called CLL?

In fact, chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adults. In the United States, the disease affects about 5 out of 100,000 people. The American Cancer Society estimates that there will be about 18,700 new cases of CLL in 2023 alone. To put this into perspective, more than 238,000 new cases of lung cancer (one of the most common cancers) are expected to be reported in 2023. So, while CLL may not seem that common, it is one of the most common types of leukemia.

What are the symptoms of CLL?

As we mentioned earlier, some people can have CLL without any symptoms . It can take months or even years for symptoms to appear. The most common symptoms are:

• Fatigue: CLL can affect your red blood cells, causing anemia. Fatigue is a common symptom of anemia.
• Fever: A fever is a sign of infection. Because CLL affects healthy white blood cells, you are more likely to get infections.
• Swollen lymph nodes in the neck, armpits, groin, or abdomen.
• Night sweats.
• Unexplained weight loss.
• Pain or a feeling of fullness under your ribs: CLL can affect your liver or spleen. When cancer cells accumulate in these organs, they can swell.

Why does CLL develop? What are the risk factors?

Chronic lymphocytic leukemia (CLL) develops when certain mutations, or changes, occur in our chromosomes and genes during our lifetime. However, medical researchers are still not sure what causes these changes. However, they have identified several risk factors that may affect it:

• Family history: Research has shown that if one of your close relatives, that is, your mother, father, siblings, or children, has CLL, your risk of developing CLL may increase by two to four times.
• Age: On average, patients are about 71 years old when diagnosed with CLL.
• Sex: Men are more likely to develop CLL.
• Exposure to Agent Orange: Research has shown a link between Agent Orange, a chemical used during the Vietnam War, and CLL.
• Monoclonal B-cell lymphocytosis: In this condition, you have more of a single type of B-cell in your blood than normal. If you have this condition, you have a small risk of developing CLL.

What are the possible complications of CLL?

CLL affects your red blood cells, white blood cells, and platelets. Think about it, red blood cells carry oxygen throughout the body. White blood cells protect us from disease. Platelets help blood clot. So, when you lose these healthy blood cells and platelets, you can have complications like:

• Lymphoma: Between 2% and 10% of people with CLL may develop a type of cancer called lymphoma.
• Skin cancer, lung cancer, or colon cancer: CLL weakens your immune system, making it less able to protect you from invaders, including cancer cells. This can increase your risk of developing other types of cancer.
• Anemia: Anemia can develop when there are not enough red blood cells to carry oxygen throughout the body.
• Thrombocytopenia: CLL can affect your platelet supply. This can cause bleeding.
• Frequent infections: Without enough healthy white blood cells, you are more likely to develop bacterial, fungal, or viral infections.
• Autoimmune diseases: Some people with CLL may develop conditions such as autoimmune hemolytic anemia.

How is CLL diagnosed?

When you go to see a doctor, he or she will ask you about your symptoms. Then, they will perform a physical exam and may order some tests, such as:

• Complete blood count (CBC) and differential: This test measures the number of red blood cells, white blood cells, and platelets in your blood. It also checks the amount of hemoglobin (the protein that carries oxygen) in your red blood cells.
• Peripheral blood smear: A medical laboratory technician examines your blood cells under a microscope to check for cancer cells.
• Flow cytometry: This lab test can provide more information about your blood cells. In CLL, it is used to determine exactly whether your white blood cells contain CLL cells.
• Genetic tests: Doctors use tests like fluorescent in situ hybridization (FISH) and immunoglobulin heavy chain (IGHV) to examine your chromosomes and genes. Understanding what changes have occurred in these chromosomes and genes can help doctors decide how to treat CLL.

Stages of CLL

Doctors determine the stage of a cancer to plan treatment and predict the prognosis. There are two main methods used to stage CLL: the Rai staging system and the Binet staging system .

Sometimes, when you read these stages in numbers and letters, you may feel a little scared and uncomfortable. You may even think, "Is this how my illness is described in a formula?" Doctors understand that. If you are not clear about what is being said, or if it is burdensome to you, please ask your doctor to explain how this stage system applies to your condition.

Rai staging system

This method classifies CLL according to the likelihood of it getting worse and whether treatment will be needed:

• Low risk (formerly known as Rai stage 0): You have lymphocytosis (an increase in the number of lymphocytes), and there are abnormal white blood cells in the blood and/or bone marrow.
• Intermediate risk (formerly known as Rai stage I or stage II): You have lymphocytosis, swollen lymph nodes, and an enlarged spleen and/or liver.
• High risk (formerly known as Rai Stage III): You have anemia or thrombocytopenia (low platelet count).

Binet staging system

This method is based on your blood cell and platelet counts, as well as the number of areas with swollen lymph nodes in your body:

• Stage A: You do not have anemia (low red blood cell count) or low platelet count. However, you have swollen lymph nodes in at least two places on your body. For example, you may have swollen lymph nodes in your neck and groin.
• Stage B: There are swollen lymph nodes in three places on the body, or the liver or spleen is swollen. However, there is no anemia, and the platelet level is normal.
• Stage C: You have anemia and swollen lymph nodes in three or more places on your body.

How is CLL treated?

Treatment options are determined by your symptoms and test results. For example, if you have early-stage CLL, your doctor may recommend a strategy called "watchful waiting/active surveillance." This involves carefully monitoring your general health, symptoms, and test results without starting treatment.

The results of genetic tests can also affect treatment decisions. For example, certain genetic changes may mean that your condition may get worse quickly, or that standard CLL treatments may not work as well as expected.

The most common treatments for CLL are targeted therapy and chemotherapy . Sometimes radiation therapy is used to reduce the symptoms of CLL. Each of these treatments can cause different side effects. Your doctor will clearly explain the benefits, side effects, and possible long-term complications of the treatment you are receiving.

Targeted therapy

This treatment works by targeting cancer cells. In chronic lymphocytic leukemia, this treatment works by stopping the growth of cancerous white blood cells. Some targeted therapies kill cancer cells without harming healthy cells. Some of the drugs used for this are:

• Bruton's tyrosine kinase (BTK) inhibitor therapy: This treatment blocks an enzyme that helps B-cells make more white blood cells. Examples: ibrutinib (Imbruvica®) , acalabrutinib (Calquence®) , and zanubrutinib (Brukinsa ®) .
• BCL2 inhibitor therapy: The drug venetoclax (Venclexta®) blocks a protein called BCL2 found in leukemia cells, including CLL cells. This treatment can kill leukemia cells or make them more sensitive to other anticancer drugs.
• Monoclonal antibody therapy: This is a type of immunotherapy. Monoclonal antibodies are a type of antibody made in a laboratory. They stop the growth of cancer cells or kill cancer cells. Examples: rituximab (Rituxan®) and obinutuzumab (Gazyva®) .

Chemotherapy

Your doctor may use chemotherapy as the primary treatment for chronic lymphocytic leukemia. Some of the most common chemotherapy drugs used for CLL are:

• Fludarabine (Fludarabine - Fludara®)
• Chlorambucil (Chlorambucil - Leukeran®)
• Cyclophosphamide (Cytoxan®)
• Bendamustine (Bendamustine - Treanda®)

Immunotherapy

This treatment method works by restoring or strengthening your immune system, helping to destroy cancer cells or slow their growth.

For CLL that has not responded to chemotherapy, has come back (recurrent) CLL, or is getting worse, doctors may use the immunotherapy drug lenalidomide (Revlimid®) .

Medical researchers are also studying chimeric antigen receptor (CAR-T) therapy for CLL patients who do not respond to standard treatments.

How long can you live with CLL?

Chronic lymphocytic leukemia (CLL) usually progresses very slowly. You can live with CLL for years before you have symptoms. Once symptoms do appear, doctors have very effective treatments that can put CLL into remission . This remission from CLL usually lasts for several years before the disease comes back. However, your doctor may recommend other treatments that can put CLL into remission again. CLL is not completely curable, but people with the disease can live long, full lives.

The National Cancer Institute estimates that 87.9% of patients with CLL are alive five years after diagnosis. However, when considering these survival rates, it is important to remember that these are estimates based on the experience of a large group of patients with CLL. Many factors can affect these survival rates, including your general health, the stage of your disease at diagnosis, and how well your disease responds to treatment. If you have questions, ask your doctor what to expect based on your situation.

What happens in the end-stage of CLL?

The term "end-stage" means that treatments are no longer effective in controlling or stopping the CLL disease. At that point, you may have life-threatening infections or uncontrolled bleeding that doctors may not be able to cure.

Can this situation be prevented?

There is currently no known way to prevent CLL.

What is it like to live with CLL?

It depends on your situation. You can have CLL without any symptoms. If you have symptoms, there are treatments to reduce them and manage the disease. However, the disease will not go away completely.

Here are some suggestions that can help you while living with CLL:

• Protect yourself from infections: People with CLL are at increased risk of developing infections. Some infections can be life-threatening. Ask your doctor about which vaccines are right for you.
• Pay attention to your general health: You may be at increased risk of developing skin cancer, lung cancer, or colon cancer. Ask your doctor about cancer screening tests.
• Manage stress: Many people with CLL go through cycles of remission and relapse. As the disease progresses, you may feel anxious and fearful. If so, ask your doctor about programs or services that can help you manage your stress.
• Eat a healthy diet: Some CLL symptoms may cause you to lose your appetite. Talk to your doctor about getting advice from a nutritionist. If your appetite is good, try to eat a balanced diet that includes lean proteins, whole grains, fruits and vegetables, and healthy fats. This can improve your overall health.
• Exercise: Exercise helps you manage stress and keep you happy.
• Take it easy: CLL can make you feel very tired. Take a break when you feel like you need it.
• Know what to expect: Knowledge is power. Ask your doctor for signs that your condition may be getting worse. If so, your doctor may recommend other treatments that can help manage your CLL better.

What questions should I ask my doctor?

You might want to ask questions like these:

• What type of chronic lymphocytic leukemia do I have?
• I have no symptoms. When should I start treatment?
• What treatment options do I have?
• Will I have to take treatment forever?
• Will treatment put my condition into remission?

Finally, things to remember (Take-Home Message)

Chronic lymphocytic leukemia (CLL) is a type of leukemia that is most common in adults. You can have this condition for years without any symptoms. If you have CLL, you may not need to start treatment right away. Although doctors cannot cure it completely, there are treatments that can relieve CLL symptoms and put the disease into remission . Some people with CLL live for years.

Living with a chronic disease like CLL isn't always easy. You may go through several cycles of remission and recurrence. During each cycle, you may worry about what will happen next. Your doctors understand what it's like to live with a chronic disease. They will be happy to answer any questions you may have and help you in any way they can. So, never be afraid to talk to your doctor about your concerns.

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