Chronic Lymphocytic Leukemia (CLL) is a slow-growing cancer that begins in the B-lymphocytes, which are vital white blood cells of the immune system. CLL makes patients immunocompromised, a serious complication that often exists from the time of diagnosis, even before treatment begins. This immunodeficiency increases susceptibility to infections, which are often the primary cause of illness and death in CLL patients. The heightened vulnerability results from a failure of the entire immune system to function correctly.
The Mechanism of Immune Dysfunction in CLL
The core problem in CLL is the overproduction of dysfunctional, cancerous B-lymphocytes. These abnormal cells accumulate in the blood, bone marrow, and lymph nodes, but they are unable to perform their main role of producing effective antibodies. This defect leads to hypogammaglobulinemia, a deficiency in protective proteins called immunoglobulins, which is the most significant driver of infection risk. Hypogammaglobulinemia is present in many patients at diagnosis and often worsens as the disease progresses.
The failure to produce functional antibodies occurs because malignant B-cells crowd out and suppress healthy B-cells responsible for normal immune responses. Even before treatment, a substantial number of patients, about 20% to 60%, may show low levels of immunoglobulin G (IgG). This antibody deficiency is compounded by defects in other immune cells, meaning the entire immune response is compromised.
T-cells, which are responsible for cellular immunity and fighting off viruses and fungi, also become dysfunctional in CLL. Interaction with cancerous B-cells causes T-cells to enter a state of “exhaustion,” making them less effective at killing infected or cancerous cells. This exhaustion reduces proliferation and function, even if T-cell numbers appear normal or elevated. CLL cells further inhibit T-cell activity by releasing chemical signals, contributing to the body’s inability to mount a proper defense.
Infection Risk and Specific Vulnerabilities
Immune failure places CLL patients at a significantly higher risk for various infections, which account for a large percentage of disease-related deaths. Bacterial infections are the most common, often affecting the respiratory tract, including the lungs (pneumonia) and sinuses. The deficiency in functional antibodies makes patients vulnerable to encapsulated bacteria, such as Streptococcus pneumoniae.
Compromised T-cell function also makes viral infections a serious threat. CLL patients are susceptible to infections like influenza and COVID-19, and the reactivation of latent viruses, such as the varicella-zoster virus (VZV) causing shingles. Infections commonly affect the skin, soft tissue, and the urogenital tract.
The risk of infection increases dramatically when patients require CLL treatment. Many therapies, including chemotherapy, targeted agents like Bruton’s tyrosine kinase (BTK) inhibitors, and anti-CD20 antibodies, further suppress the immune system. Anti-CD20 antibodies, for instance, cause a long-lasting depletion of B-cells, severely impairing the body’s ability to create new antibodies. Newer targeted therapies, while often less broadly immunosuppressive than older chemotherapy, can still carry specific risks, such as increased susceptibility to certain fungal infections or prolonged neutropenia.
Managing Immunodeficiency in CLL Patients
Managing immunodeficiency in CLL requires a proactive strategy beginning immediately upon diagnosis. A foundational protective measure is the strict avoidance of live-attenuated vaccines, as these can cause illness in an immunocompromised host. Patients should receive inactivated or non-live vaccines for common threats.
Recommended Vaccinations
Vaccinations are most effective when given early in the disease course, before the immune system is weakened by treatment or disease progression. Clinicians often recommend a specific two-shot regimen for pneumococcal protection, using PCV13 followed by PPSV23 several months later. Recommended non-live vaccines include:
- The annual influenza shot.
- The non-live recombinant shingles vaccine (Shingrix).
- Pneumococcal vaccines.
Even when vaccinated, the immune response in CLL patients may be suboptimal, meaning protection is not guaranteed.
Hygiene and Monitoring
Simple, daily hygiene practices remain important, including frequent and thorough hand washing and avoiding close contact with sick individuals. For patients with severe hypogammaglobulinemia and a history of recurrent bacterial infections, Immunoglobulin Replacement Therapy (IgRT) may be recommended. This treatment administers purified antibodies pooled from healthy donors, replenishing deficient immunoglobulin levels and reducing the rate of serious bacterial infections. CLL patients must be vigilant for any signs of infection, such as fever, and report them immediately to their medical team, as early detection and treatment are paramount to preventing life-threatening complications.