Patients with chronic lymphocytic leukemia (CLL) are at higher risk for infections due to the myelosuppressive and immunosuppressive effects of the disease and its associated therapies. As infections are a leading cause of death for patients with CLL, anti-infective prophylaxis is important.

Patients with CLL have immune dysfunction, and, when they are treated with targeted therapy, immune dysfunction initially worsens during the first few months of treatment. Therefore, it is clear that we need to screen for infection, treat early, and vaccinate patients before starting CLL therapy.

<br>

It is critical to be attentive to possible infections. BTK and PI3K inhibitors have been associated with an increased risk of Pneumocystis jirovecii pneumonia, and prophylaxis is recommended for patients who will receive a PI3K inhibitor. It is recommended that patients with CLL be screened for any latent infection, partially controlled infection, or ongoing bacterial, viral, or fungal infection at diagnosis and before initiating a BTK or PI3K inhibitor.

<br>

It is also recommended that our patients with CLL stay up to date on protective vaccines. The best time for patients to receive vaccines is prior to the initiation of first-line treatment. While some research indicates that patients with CLL may have a reduced antibody response to vaccines, they still develop some immunity—and some immunity is better than no immunity. I do not feel that we have enough evidence to recommend treatment discontinuation to receive vaccines. A recently published report confirmed that there is no benefit to temporarily discontinuing BTK inhibitor therapy at the time of COVID-19 vaccination. Finally, it is important to remind patients with CLL that they should not receive live vaccines.

<br>

In addition to prophylaxis, monitoring for neutropenia is particularly important in patients with CLL. Depending on the severity, it may be necessary to modify treatment by either holding or reducing the dose, according to the clinical scenario. The prompt administration of granulocyte colony-stimulating factor to reduce the severity and duration of neutropenia is usually effective. However, in cases of prolonged neutropenia, antibacterial and antifungal prophylaxis should be implemented.

<br>

Another important way to keep patients with CLL healthy is to identify those who may benefit from immunoglobulin replacement therapy. These are usually patients who have hypogammaglobulinemia and a history of recurrent infection, most commonly recurrent sinusitis or tonsillitis. At our center, we follow contemporary guidelines for the administration of immunoglobulin replacement therapy in patients with hypogammaglobulinemia. We typically administer it intravenously (every 3-4 weeks) or subcutaneously (weekly), and we tailor the treatment duration and the interval between administrations to maintain an IgG level of at least 500 mg/dL.

<br>

Overall, these important interventions can keep our patients with CLL healthy and can help them avoid infection and maintain as much control as possible over the risks that they are exposed to.