This month, Mitchell Smith, MD, answers a question about the treatment course for an indolent presentation of mantle cell lymphoma.
A 57-year-old woman with a history of chronic immune thrombocytopenic purpura (ITP) (diagnosed in 1994) now presents with a WBC 6.6 with 67 percent lymphocytes and 27.2 percent granulocytes, hemoglobin 14, mean corpuscular volume 91.2, and platelet count 23,000 (better than usual for her). Flow cytometry on the peripheral blood revealed a monoclonal kappa B-cell population co-expressing CD5 and CD23. CD38 expression was not detected. FISH test results were positive for CCND1-IGH (translocation T(11;14) gene rearrangement in 75%).
These findings are consistent with mantle cell lymphoma (MCL). PET-CT findings were unremarkable. The bone marrow demonstrates involvement by MCL.
The lymphoma is positive for CD 20, CD5, cyclin D1, BCL-2, and Pax 5. It is negative for CD3 and CD10. A Ki-67 stain shows a proliferation index of 40 to 50 percent. She also had an EGD and colonoscopy, which were unremarkable. She has no constitutional symptoms. I feel that she has an indolent subtype of MCL with leukemic presentation. As she is asymptomatic, I am inclined to recommend close observation alone. Is this appropriate?
EXPERTS MAKE THE CALL
Yes, I think you are exactly correct to advise observation. There are a percentage (10-20%) of MCL cases that behave indolently, often with this chronic lymphocytic leukemia (CLL)–like presentation, though more commonly described in older male patients.
One note of concern would be the Ki-67 stain showing a proliferation of 40 to 50 percent, which is higher than usually seen in this type of presentation. It might be worth asking the pathologist to be sure just the lymphoma cells – not normal marrow precursors – were counted. (Note: When re-evaluated, the pathologist said Ki-67 was not evaluable as it was not possible to separate lymphoma from normal hematopoietic cells.) Ki-67 is an important prognostic factor in MCL. Knowing this value would not change the recommendation, but it would increase the comfort level for observation.
The long history of ITP, suggesting underlying immune dysfunction, is interesting.
There is other information that would be helpful in making a decision, but the answers to the questions would not alter the recommendation. For instance, has the patient had a splenectomy? If not, is her spleen enlarged? Also, has she received rituximab in the past for her ITP?
If and when this indolent presentation of MCL eventually requires therapy, I have used single-agent rituximab, or the combination of bendamustine plus rituximab if the disease pace has picked up by then.
Even at age 57, I would be hard-pressed to recommend high-dose chemotherapy followed by autologous hematopoietic cell transplantation, unless the disease had changed character.
This decision would be an area of some disagreement as young, fit patients with low mantle cell IPI (MIPI) do well with intensive therapy, however, they also do well with less intense therapies (See 2015 ASH Annual Meeting abstract #2702 – Initial therapy for mantle cell lymphoma with abbreviated R-CHOP followed by Y90-ibritumomab tiuxetan: Ten year follow-up of the phase 2 ECOG-ACRIN Study E1499).
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