Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
Patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) have a hard time fighting infections and other diseases because their immune systems don’t function as well as those of healthy people. In this interview, Dr. Brian Koffman spoke with Dr. William Werbel, an assistant professor of medicine at Johns Hopkins University who studies how to prevent infections in patients who have had transplants or cancer.
What does it mean to be immunocompromised?
At a basic level, being immunocompromised means that your immune system doesn’t function as well as a healthy person’s. There are many different causes of immunosuppression, including genetic conditions, medications, organ transplants, and blood cancers. All these types of immunosuppression behave differently and lead to different susceptibilities. Many different factors affect how immunocompromised someone is, including age, medical conditions such as diabetes, and even the health and integrity of their skin.
All CLL / SLL patients are immunocompromised to some lesser or greater extent. Patients with CLL tend to be older and have other medical conditions, which means their immune system already isn’t working quite as well as a young, healthy person. Then, CLL itself broadly impairs immunity. It affects the immune cells that make antibodies (B cells), and sometimes, it also impairs certain immune cells that help fight off infections, especially viral infections (T cells). B and T cells are part of the adaptive immune system, but CLL can also impair the innate immune system.
What is the difference between the innate and adaptive immune system?
The innate immune system is important for the early, more primitive, and less specific responses to infections and includes cells like macrophages, neutrophils, and natural killer cells. This part of the immune system is always active and less targeted than the adaptive immune system. The cells of the innate immune system are constantly surveilling the body, and they sound the alarm if they detect foreign pathogens in the body.
The adaptive immune system is much more specific in its responses and consists of B cells (and the antibodies they produce) and T cells. However, the adaptive immune system takes more time to build up an immune response because it involves firing up a targeted response to pathogens it has encountered. The targeted response is quicker and more robust when there has been prior exposure, either through vaccination or past infections. For instance, these cells remember and selectively attack a specific strain of influenza or COVID-19. Vaccines prepare the adaptive immune system to be ready to attack those specific viruses in the future.
What are the challenges of using vaccines in immunocompromised patients?
Often, immunocompromised patients are on medicines that cause immunosuppression because they have conditions where you don’t want the body attacking new or different cells. For instance, if you have a stem cell transplant, organ transplant, or CAR-T therapy, you don’t want the body mounting a robust immune response to clear out the new cells. Immunosuppressive drugs are also used in patients with autoimmune conditions because you want to prevent the body from attacking its own cells. Autoimmune hemolytic anemia is the most autoimmune disease seen in CLL. The flip side of suppressing the immune system is that immunocompromised patients are not very good at mounting immune responses to pathogens and vaccines. So, for something completely new like COVID-19, it often takes three or more vaccine doses for the body to generate some adaptive immune memory.
The disease itself, its complications, and its treatments can all impair immunity.
What advice do you have for immunocompromised patients?
Vaccination is effective and recommended but expect that you will need more vaccine doses and boosters than healthy people. Use common sense precautions to reduce risk during times of high virus circulation, such as avoiding crowds, wearing a mask, and washing hands. Be aware that there are passive immunization strategies available where patients can receive already formed antibodies such as intravenous immunoglobulin (IVIG), convalescent plasma, and monoclonal antibodies (similar to Evusheld in the past and Pemgarda now).
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Watch the interview here:
