What Is Chronic Lymphocytic Leukemia?

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia. It is a slow cancer that affects lymphocytes, which are a type of white blood cell. Lymphocytes include B cells, T cells and natural killer cells, all of which have very important immune functions. Because CLL disrupts their function, it has a major impact on the immune system.

CLL patients tend to be middle-aged and older: Around 75% are over 65 when they are diagnosed. It is rare in children. The progress of CLL is slow. It can even be asymptomatic in its early phase. Most patients live 5 to 10 years after diagnosis: The five-year survival rate is around 83%. However, if the patient is older at diagnosis, this survival metric is lower.

CLL Disrupts the Immune System

As mentioned, a key feature of CLL is dysregulation of both the innate and adaptive immune responses. The innate immune system delivers the first response to invading pathogens. This response is not specific to a particular pathogen. The system recognizes pathogens as “non-self” (i.e., not part of the body) and directs certain cells and proteins against them.

Adaptive immunity fights pathogens more directly and accurately. As our immune system encounters pathogens, it learns about their structure and protein signature, remembering this in case of future encounters. Vaccination works by training the adaptive immune response.

Due to this disruption of immune responses, infections are the main cause of death in CLL patients. Additional supportive care is essential to compensate for their compromised immune systems.

What Supportive Care Is Suitable for CLL Patients?

Vaccination against seasonal influenza and Streptococcus pneumoniae is recommended, with the sequence of vaccines for the pneumonia-causing pathogen being PCV13 followed by PPSV23. Early vaccination is important to give the most benefit.

Immunoglobin substitution using IVIG is also suggested. There is evidence that it can decrease bacterial infection rates in CLL patients who have a condition called severe hypogammaglobulinemia. The European Medicines Agency (EMA) has specific criteria to qualify CLL patients for immunoglobin substitution. Your physician should be aware of these. They are described in the article.

In addition, all the standard lifestyle practices for immunocompromised individuals are important. CLL patients should maintain a clean environment, personal hygiene, and a healthy diet. Furthermore, if the patients need care, their carers should be informed of the importance of cleanliness and the risk of infection.

Finally, extra care should be taken during outbreaks, epidemics, and pandemics. We are all well informed on what taking care during a pandemic means! Wearing masks, using hand sanitizer, keeping a certain distance from people in public, and staying home when possible have become normal all over the world during the COVID-19 pandemic. Immunocompromised individuals are encouraged to apply such practices during seasonal influenza outbreaks and epidemics as well as during any other type of infectious disease crisis.

The article also mentions that physicians should consider reducing the number of in-person consultations with CLL patients and replacing them with phone calls to reduce the risk of SARS-CoV-2 infection. While there is very little data on SARS-CoV-2 and CLL, patients with this cancer are in a high-risk group.

What Direct Treatment Is Used for CLL?

Because the initial course of CLL is slow, immediate treatment is not required. The strategy that is employed is called “watch and wait”: careful and regular observation of the impact of CLL on the immune system, with a response being initiated when the patient becomes immunocompromised.

When treatment does become necessary, it is rare to use chemotherapy-based regimens. Chemoimmunotherapy, which combines antibody and drug treatment, has shown some success in a limited group of patients. Opportunistic infections are a danger with both chemotherapy and chemoimmunotherapy, so their use should be weighed carefully.

Inhibitors of pathways associated with CLL proliferation have also been trialed. Called BCR inhibitors, these drugs are well tolerated and have positive impact in the short term, but longer-term data shows severe opportunistic infections associated with their use. More recent evidence shows that BCL-2 inhibitors are promising. They increase the apoptosis (cell death) of CLL cells. They are both effective and well tolerated provided the drug regimen is carefully planned to avoid certain side effects.

What Should I Talk to My Doctor About?

If you or a member of your family are diagnosed with CLL, ensure that you talk to the doctors about the longer-term strategy. What tests will they do during the “watch and wait” phase? What results should you record? How can you improve your home environment, diet and so on to reduce infection risk? What CLL treatments might be available to you after the CLL starts to strongly affect your immune system, based on your medical history, age, existing medication and so on?

You should also talk to your doctor about your annual vaccination plan, which may now also include a COVID-19 vaccine alongside the seasonal influenza and S. pneumoniae ones.

Note: The article “Immune Dysfunction in Patients with Chronic Lymphocytic Leukemia and Challenges during COVID-19 Pandemic” was written and accepted for publication before the approval of a COVID-19 vaccine. Therefore, some of the information on COVID-19 infection and treatment is out of date.