Approaching a Case of Chronic Lymphocytic Leukemia


William G. Wierda, MD, PhD:A 78-year-old female who seems to be otherwise healthy presents with an initial lymph node that can be palpated and, on physical exam, has a palpable spleen. The blood counts show an elevated white blood cell count with a lymphocyte predominance, and the patient is mildly anemia with a hemoglobin of 10.4, no evidence of thrombocytopenia with a platelet count of 150. And the patient had a standard workup for chronic lymphocytic leukemia [CLL], which confirmed this diagnosis based on the flow cytometry. We evaluate for the typical markers, those being CD5, CD19, and CD23. And typically we look for light chain restriction to show clonality.

The other feature in terms of the patient’s blood counts is that she does have a low neutrophil count, and we see that and it’s probably more of a dilutional effect in doing the blood count and getting the differential because they count a limited number of cells. And most of those cells are going to be lymphocytes, so you can see neutropenia or low neutrophil counts because of this dilutional effect. The patient doesn’t have the same risk for infection as an individual who, for example, has had chemotherapy and has neutropenia because of recent chemotherapy.

In terms of prognostic factors that were evaluated for the patient, the patient has had beta 2- microglobulin, and that’s slightly elevated. We see that in older patients, particularly because there is some renal insufficiency in those individuals. And that tends to raise the beta 2-microglobulin. And other features include FISH [fluorescence in situ hybridization], which evaluates for specific cytogenetic abnormalities. And in this patient, the patient has trisomy 12, and the immunoglobulin heavy chain variable gene sequencing revealed that the patient has a mutated immunoglobulin chain. And we’ll discuss the implications and ramifications of those features as we go through the case.

So the patient has a diagnosis of CLL. Bone marrow involvement is always present, and so the patient had a bone marrow biopsy. You don’t need a bone marrow biopsy to get the diagnosis of CLL because they typically have an elevated white blood cell count, and the testing, including the prognostic testing, can be done on the blood. So we don’t require a bone marrow biopsy for diagnosis or prognostic evaluation.

The features of this patient make me think that they are headed toward treatment and will need treatment relatively soon or in the feature. There is one particular feature for this patient, and that is the hemoglobin. I usually use a hemoglobin of 10 to initiate therapy. This patient had a hemoglobin of 10.4. In terms of our staging that we use, particularly the Rai staging system, this patient had a hemoglobin of less than 11, which makes this patient have a Rai stage III disease, which is a higher-risk category. And some people use 11 as their cutoff for the hemoglobin to start therapy. Some use 10. Patients who are in their 70s and 80s tolerate a lower hemoglobin less well than younger patients or more fit patients. So this patient, if you use the strict criteria, is approaching treatment. Maybe today she doesn’t need treatment, but she is going to need treatment relatively soon. And I don’t see any benefit to waiting until this patient’s hemoglobin drops to below 10 to start treatment.

In terms of other testing that I would recommend for this patient and other patients who are evaluated when one is considering treatment, the one missing piece of information for this particular case is mutation analysis forTP53. SoTP53is the gene that’s located at 17p or located on the short arm of chromosome 17. While this patient had FISH and was evaluated for 17p deletion and didn’t have that abnormality, the patient could still have a mutation inTP53and that has clinical implications and is useful and important information that we should have. So I would add that to the initial workup for this patient.

This patient proceeded and was initiated on treatment, and the treatment that this patient received was ibrutinib-based therapy. And the patient achieved a response. Most patients who start and are treated with ibrutinib therapy achieve a partial remission, and that happens relatively soon. Complete responses are uncommon but become more common as patients stay on treatment, and that usually takes several years to occur. So the complete remission rate for a group of patients treated with ibrutinib is relatively low after 1 year on treatment. But it rises and is upward of 25% to 30% after 3 years on treatment. So initially, most patients get a response, most responses are partial responses. Patients remain on treatment to maintain their response, and their response can deepen.

Transcript edited for clarity.

An Elderly Woman With CLL

  • A 78-year—old female presented with symptoms of fatigue and loss of appetite for the past six months
  • PMH: recurrent bronchitis during past 12 months, treated with antibiotics
  • PE: vital signs WNL, right cervical lymphadenopathy, spleen palpable 5 cm below costal margin, otherwise well-appearing
  • Laboratory findings:
    • WBC, 53,000; 76% lymphocytes
    • Hb; 10.4 g/dL
    • Platelets; 150 X 109/L
    • ANC; 180/mm3
  • Flow cytometry; CD5+, CD19+, CD23+
  • Cytogenetics, FISH: trisomy 12; IgVH mutated
  • β2M, 3.6 mg/L
  • BM biopsy; diffuse infiltration by CLL
  • Diagnosis; chronic lymphocytic leukemia
  • The patient was treated with ibrutinib and achieved a complete response to therapy after 4 months
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