Swollen lymph nodes mean the immune system is working to fight something, but it can be hard to pinpoint its target. Swollen lymph nodes are the most common symptom of chronic lymphocytic leukemia (CLL). About 20 percent of people with leukemia have swollen lymph nodes before they’re diagnosed. If you’re living with CLL, swollen lymph nodes can signal several conditions, from infection to a complication. They may also be unrelated to your blood cancer.

Lymph nodes play a critical role in the body, filtering harmful substances out of lymph fluid. Lymph nodes swell when there’s a problem with your body, such as an infection or cancer cells.

Read on to learn about five potential causes of swollen lymph nodes related to CLL and to know when it’s time to talk with your doctor.

1. Cancer Cells Build Up and Make Lymph Nodes Swell

Most people with CLL don’t have symptoms at first, and they may learn they have CLL after getting a routine blood test. However, some people do experience early symptoms, most commonly swollen lymph nodes. Physical examinations show that from 50 percent to 90 percent of people with CLL have enlarged lymph nodes, either localized to one region or generalized (beyond a specific area).

Swollen lymph nodes are the most common symptom of chronic lymphocytic leukemia.

Swollen lymph nodes from CLL result from a buildup of abnormal lymphocytes (a type of white blood cell) in lymph nodes, which causes the glands to swell. Most of the time the swollen lymph nodes occur in the groin, stomach, armpit, or neck. “I have CLL, no treatment yet, and have a large lump in the lymph node in my groin,” one MyLeukemiaTeam member wrote.

Swollen lymph nodes caused by CLL are often painless. “I’ve been one year with CLL, with swollen lymph nodes but no pain,” another member shared.

However, some people with CLL have swollen lymph nodes that get big enough to press on nerves or organs and cause pain.

Other early-stage symptoms of CLL include:

• Fatigue
• Ongoing fever
• Unintentional weight loss
• Night sweats

2. Swollen Lymph Nodes May Mean CLL Is Progressing

Swollen lymph nodes may mean that CLL is progressing and it’s time to begin treatment. When doctors look at CLL staging, they assess whether your CLL has a low, intermediate, or high risk of making you sick. Swollen lymph nodes place you in the intermediate or high-risk group.

If you’re living with CLL, swollen lymph nodes may mean it’s time to start cancer treatment if you haven’t yet.

“When my CLL was in its worst stages, the lymph nodes in my neck and my groin were very enlarged and at times very uncomfortable,” one member wrote.

Since swollen lymph nodes can be a sign of more advanced stages of CLL, this symptom may mean your doctors will recommend it’s time to start treatment. Not everyone with CLL will need treatment, but it’s generally recommended for people with very enlarged or painful lymph nodes and other disease-related symptoms.

3. CLL Can Change Into a More Aggressive Cancer

In rare cases, CLL can transform into a more aggressive type of cancer. Swollen lymph nodes may be a sign of this transformation.

When CLL changes into another form of cancer, it’s called “Richter transformation” or “Richter’s syndrome.” This condition occurs in 2 percent to 10 percent of people with CLL. Of those, most people develop diffuse large-B cell lymphoma (DLBCL) and others develop Hodgkin lymphoma. These transformations may call for more aggressive treatment.

People with CLL who go through Richter transformation may have extremely enlarged lymph nodes, as well as weight loss and fevers. Richter transformation is more common in people with high-risk factors, such as advanced-stage CLL. If this cancer happens, it often develops a few years (usually between two and six years) after CLL was diagnosed.

4. Some CLL Treatments Can Cause Swollen Lymph Nodes

Swollen lymph nodes that are painful may indicate a tumor flare, which is a reaction to a drug. According to the Leukemia & Lymphoma Society, tumor flares are common among people with CLL taking lenalidomide (Revlimid).

A tumor flare may also cause the following symptoms:

• Fever
• Rash
• Bone pain

A flare can cause elevated lymphocyte counts and an enlarged spleen. If you’re worried that you may be experiencing a tumor flare, your health care provider can check for these signs.

5. Swollen Lymph Nodes May Be a Sign of Infection

Infections can cause swollen lymph nodes as the immune system makes more white blood cells to fight off invading germs. People with CLL are more likely to get infections because the bone marrow makes abnormal lymphocytes, which don’t turn into healthy white blood cells that would normally attack invaders. During an infection, lymph nodes can grow to half an inch or larger.

In a small number of people with CLL, swollen lymph nodes can mean the cancer is changing into a more aggressive form.

In addition, chemotherapy can increase the risk of infection because it lowers your white blood cell count. However, CLL also makes the immune system less effective and infection more likely, even if you’re not taking treatment.

Several types of infection can cause swollen lymph nodes. The most common are upper respiratory infections, such as the common cold. Other infections that can cause swollen lymph nodes include:

• Skin infections
• Influenza
• Sinus infection
• Strep throat
• Mononucleosis (also called “mono”)

“I get enlarged, painful lymph nodes in my neck during an acute viral attack,” one member shared. “They usually don’t hurt at all until I get a cold or other virus. My nodes are usually swollen anyway because of my CLL/SLL. It was how we discovered I was sick.” (The term “small lymphocytic leukemia,” or SLL, is often combined with CLL.)

In addition, people with CLL may be more prone to certain types of infection compared to people without CLL. One small study revealed that lower respiratory tract infections, such as bronchitis, were more common among people with CLL. The same study also showed a higher risk of skin infections and urinary tract infections with CLL.

Swollen lymph nodes are likely to develop near the location of the infection. For example, if you have strep throat, the lymph nodes in your neck may be swollen.

Other Potential Causes of Swollen Lymph Nodes

Sometimes swollen lymph nodes are caused by factors unrelated to CLL. Swollen lymph nodes in more than one area of the body may be a sign of a systemic condition, including:

• Toxoplasmosis (infection caused by the parasite Toxoplasma gondii)
• Some sexually transmitted infections
• Autoimmune conditions, such as rheumatoid arthritis and lupus
• Serious bacterial or viral infections, such as typhoid fever and measles
• Another malignancy, like breast cancer, which can cause swollen lymph nodes in the armpit
• Recent vaccination, especially receiving a shot of the COVID-19 vaccine

When To Talk to a Doctor About Swollen Lymph Nodes

Swollen lymph nodes may be a sign that your cancer is getting worse, so it’s important to report this symptom to your cancer care team. They can determine what’s causing your swollen lymph nodes and offer treatment options, if needed. Radiation may help treat painful swollen lymph nodes due to CLL.

Talk With Others Who Understand

MyLeukemiaTeam is the social network for people with leukemia and their caregivers. On MyLeukemiaTeam, more than 19,000 members come together to ask questions, give advice, and share their experiences with others who understand life with different forms of leukemia.

Have you noticed swollen lymph nodes with CLL? Have you talked with your doctor about what’s causing them? Share your experience in the comments below, or start a conversation by posting on your Activities page.