Approaches to Initiating Therapy for a Patient With CLL and Worsening Symptoms

Anthony Mato, MD, MSCE: Let’s talk about a case of a typical patient, a 67-year-old woman who presents with lymphocytosis. It was noted on routine examination with their PCP [primary care physician]. Her past medical history is notable for GERD [gastroesophageal reflux disease], and she’s on a PPI [proton pump inhibitor] for mild indigestion. One of the questions I have is does she really need to be on that?

Physical examination is notable for cervical lymphadenopathy, with no palpable spleen and no palpable liver, and a great performance status. Laboratory studies show a white blood cell count of 51,000 per mm3 with 80% lymphocytes. Hemoglobin is normal at 12.7 g/dL. Platelets are normal at 256 per mm3. She has a normal neutrophil count, and her LDH [lactate dehydrogenase] level is within normal limits. There’s a high suspicion for CLL, obviously, and other lymphoproliferative disorders in leukemic phase. To distinguish 1 from the other, you can perform flow cytometry on a peripheral blood sample as well as look at peripheral smear. Flow cytometry in this case revealed the CD5 positive, CD19 positive, CD20 dim, CD23 positive, malignant clonal B-cell population. This is fairly typical for CLL.

Of course, there’s no perfect immunophenotype that’s absolutely associated with any lymphoproliferative disorder, but here we have all the markers going for CLL. That’s our clinical impression. Next we delve into performing prognostic evaluation. The patient has FISH [fluorescence in situ hybridization] testing without any obvious abnormalities, with the exception of deletion 13q and IGHV unmutated. Some are favorable by FISH. Some have unfavorable prognostic markers, in terms of IGHV status. Some people like to perform a model called the CLL-IPI [international prognostic index]. To do that you have to have a beta-2-microglobulin that’s normally at 3.5 µg/mL and bone marrow biopsy that shows 67% lymphocytes with the diffuse pattern. In this case, this seems like a relatively early stage patient. Stage would be between 0 and 1, depending on whether you thought that lymph node was enlarged or not. I probably wouldn’t feel strongly to get a bone marrow biopsy, but many patients in our practice have already come with the work-up and a diagnostic evaluation, and they have them.

Of course, this patient is early stage and asymptomatic. She’s observed for 2 years and then develops progressive fatigue and night sweats. Kristen, in hearing this case and the most recent update about fatigue and night sweats, what would you order next? How would you approach that patient in clinic?

Kristen Battiato, AGNP-C: We’re nearing therapy because she’s having worsening or new and worsening constitutional symptoms that are impacting her ADLs [activities of daily living], given the profound fatigue and night sweats. I’d repeat our next-generation sequencing to determine if she has any new molecular mutations. I’d also repeat cytogenetics with FISH and array and make sure she doesn’t have an acquired del 17p or del 11q. Anthony, we wouldn’t image her, right? Because we don’t.

Anthony Mato, MD, MSCE: I probably wouldn’t. Taking a step backward, she has severe fatigue. I would get a CBC [complete blood count] and see if she’s anemic. Start with that. Maybe this isn’t a constitutional symptom. Maybe it’s like symptomatic anemia. The iwCLL [International Workshop on CLL] criteria do say you’re allowed to be fatigued with CLL without being anemic, but I would make sure her hemoglobin is not 9 g/dL when we see this all the time. Patients who have progressive disease by marrow infiltration, are hemolyzing, or have iron deficiency and an undiagnosed ulcer or colon cancer. Who knows, maybe her GERD really was peptic ulcer disease. When we see patients, they always get CBCs, but let’s assume she had a CBC and she has significant anemia. That might be the driver for the fatigue and the night sweats. I know you agree with me about this—we always hear night sweats, but 75% of the time they’re not true night sweats.

Kristen Battiato, AGNP-C: They’re not drenching.

Anthony Mato, MD, MSCE: Not drenching. Maybe the air conditioner doesn’t work well in the bedroom—there are lots of possibilities. But she probably needs therapy. It’s a little quick because she was stage 0 or I disease—let’s call her stage I disease—2 years ago, but some people have an acceleration of their disease. She might have at least 2 triggers to initiate therapy.

Transcript edited for clarity.