Written By Dr. Brian Koffman, MD, CM
Retired Physician
CLL/SLL Patient Advocate
Co-Founder & Chief Medical Officer Emeritus of CLL Society
CLL/SLL Patient Advocate
Co-Founder & Chief Medical Officer Emeritus of CLL Society
The First “Strike”: CLL/SLL Disease Biology
In CLL/SLL, the first “strike” of infection risk belongs to the disease itself. The immune defect in CLL/SLL is intrinsic, present in untreated patients and sometimes even before diagnosis.
The immune dysfunction is multilineage: hypogammaglobulinemia across IgG, IgA, and IgM that tracks with infection frequency and shortened survival; T-cell exhaustion and CD4/CD8 imbalance that invite viral reactivation (HSV, VZV, CMV); and weakened NK cells, neutrophils, dendritic cells, and complement that erode defense against bacteria and fungi. Even untreated, the result can be recurrent sinopulmonary and opportunistic infection, poor vaccine responses, and more secondary cancers.
The Second “Strike”: Anti-CD20 Treatment
The second “strike” of infection risk belongs to chosen treatment. While all CLL/SLL treatments bear risk of infection, anti-CD20 treatments are specially engineered to kill the very B cells that support immune response. Clearing CD20-positive B cells spares CD20-negative plasma cells, but most of those live only days to months, so once the pipeline of differentiating B cells that replenishes them is cut off, hypogammaglobulinemia may deepen within months. Recovery may be slow: B cells return in roughly 6 to 9 months after monotherapy, but 18 to 24 months once chemotherapy is added. In some, the deficit can linger for years.
Together, the two strikes of CLL/SLL and anti-CD20 treatment may leave a patient more profoundly and durably immunosuppressed than either strike alone.
Why Flu/COVID Season May Matter
- Have you had any serious infection requiring IV antibiotics or hospitalization, or had infections that kept coming back?
- Do you get frequent sinus, chest, or respiratory infections in a typical year?
- Have you ever been told that your immunoglobulin or antibody levels were low?
- Has your spleen been removed, or been told it doesn’t work well?
- Which vaccines have you had, and when? Include flu, COVID, pneumococcal, shingles, RSV.
- When was your last vaccine relative to any prior anti-CD20 (antibody) treatment?
- Has anyone checked whether a prior vaccine worked by measuring antibody levels?
- Are your close contacts and household members vaccinated?
- Do you know whom to call at the very first sign of a respiratory illness?
- Do you have a clear plan for fever or new symptoms: whom to call, and how fast?
- Does the benefit of an anti-CD20 treatment outweigh the depth and timing of the risk of the second immunological hit in this patient, at this time of year?
