Does CLL Make You Immunocompromised? Infection Risks and Immune Changes in CLL

Chronic lymphocytic leukemia (CLL) can weaken the immune system. This can happen even before treatment starts. Learn why CLL affects immunity, how treatment may change infection risk, and what you can do to help support your health. 

How CLL can weaken your immune system

CLL is a cancer of B cells. B cells are white blood cells that help fight infections.

In CLL, abnormal B cells build up in the blood, bone marrow, and lymph nodes. These cells crowd out healthy immune cells and interfere with normal immune function.

Researchers found that CLL affects both main parts of the immune system:

• Adaptive immunity, which helps the body recognize germs
• Innate immunity, which provides quick protection against infection

Because of these changes, the body may have a harder time fighting bacteria, viruses, and fungi.

For many people with CLL, immune problems begin at diagnosis. They can become worse over time. 

Low antibody levels increase infection risk

One of the most common immune problems in CLL is hypogammaglobulinemia. This means the body has low levels of antibodies, also called immunoglobulins.

Antibodies help find and remove germs. When antibody levels drop, infections can happen more often.

Researchers found that low IgG levels (a type of antibody) are linked to more severe and repeated infections. Low antibody levels become more common as CLL progresses.

This matters because infections are a major health concern in CLL. Studies found that infections account for about 30% to 60% of deaths in people with CLL. 

Your doctor may check antibody levels with blood tests. Some people with low IgG levels and repeated infections may receive immunoglobulin replacement therapy (IVIG). This treatment provides donated antibodies to help lower infection risk. 

CLL affects more than antibodies

CLL can also change how other immune cells work. T cells are an important part of the immune system. They help destroy infected and abnormal cells. Researchers found that T cells in CLL may become less effective over time. Some experts call this "T-cell exhaustion." 

Other immune changes can include:

• Lower levels of complement proteins that help fight bacteria
• Neutrophils that do not work as well as they should
• Natural killer cells that have trouble controlling infections and cancer cells

Together, these changes make it harder for the body to fight infections. 

CLL COVID-19 risk, pneumonia, and other infections

People with CLL are more likely to develop respiratory infections. Pneumonia is one of the most common serious infections. Bacteria such as Streptococcus pneumoniae and Haemophilus influenzae can cause these infections.

People with CLL may also have a higher risk of:

• Shingles
• Influenza
• COVID-19 complications
• Fungal infections

The risk often increases as CLL advances or after multiple treatments. Older age and other health conditions can also raise infection risk.

How CLL treatments may affect immunity

Some CLL treatments can further weaken the immune system. Older chemoimmunotherapy treatments often caused low white blood cell counts that lasted for months. 

Newer targeted treatments affect immunity in different ways.

BTK inhibitors may improve some immune functions over time. Researchers found that infection risk may decrease after the first several months of treatment for some people.

Venetoclax (Venclexta, AbbVie/Genentech) can cause neutropenia. Neutropenia means low levels of infection-fighting white blood cells. 

Rituximab and other anti-CD20 treatments can reduce healthy B cells for many months after treatment.

Because of this, infection prevention remains important throughout CLL care.

CLL and vaccines

Vaccines may not work as well for people with CLL. But they still help lower the risk of serious infections. 

Researchers found vaccine responses are often stronger early in the CLL course and before treatment begins. 

Experts recommend non-live vaccines for people with CLL. Live vaccines can cause problems in people with weakened immune systems.

Recommended vaccines may include:

• Influenza vaccine
• COVID-19 vaccine
• Pneumococcal vaccine
• Recombinant shingles vaccine 

Family members can also stay up to date on vaccines. This may help reduce the chance of bringing infections into the home.

Steps you can take to lower infection risk

Talk with your care team about ways to lower infection risk. These steps may help:

• Monitor antibody levels
• Stay current on non-live versions of vaccines
• Report fevers right away
• Wash your hands often

Ask if preventive medicines with antibiotics and antifungals are right for you

Key takeaways

CLL can make you immunocompromised. The condition affects antibodies, T cells, and other parts of the immune system. Infection risk can vary from person to person, but vaccines, donor antibody infusions (IVIG), monitoring, and supportive care can help reduce complications and support your health

Continue reading about CLL and the immune system: 

• How Are CLL-Related Infections Managed?
• Know Your Options Against Infections - Immunoglobulin Infusions (IVIG) for People with CLL
• Infection Prevention for CLL Patients with Dr. Meghan Thompson
• Is CLL an Autoimmune Disease? How CLL Affects the Immune System
• Immunoglobulin Therapy or Antibiotics: Which Is More Effective in Preventing CLL Patient Infections? 

Sources: 

• Can We Restore Immunocompetence in CLL?
• Immune Response Dysfunction in Chronic Lymphocytic Leukemia: Dissecting Molecular Mechanisms and Microenvironmental Conditions
• Chronic Lymphocytic Leukemia-Induced Humoral Immunosuppression: A Systematic Review
• Immune failure, infection and survival in chronic lymphocytic leukemia
• Vaccinations in Patients with Chronic Lymphocytic Leukemia
• Infections in Chronic Lymphocytic Leukemia: Evolving Risks and Prevention Strategies