Brisk Lymphocytosis with Aberrant Expression of CD5 in the Leukemic Phase of Follicular Lymphoma.
Authors: Shah Bijal D. , Sagatys Elizabeth , Zhang Ling , Moscinski Lynn C. , Sotomayor Eduardo M. 
Published: October 2019

Abstract
Abstract 5033

Background
Follicular lymphoma (FL) is generally considered to be an indolent, low-grade lymphoma. However, rarely, FL can present with a marked lymphocytosis, in a so-called leukemic phase, with a significant impact on response to therapy and outcome. We summarize here our experience with two such cases.

Case 1
Pt #1 was diagnosed with stage IVB/S (FLIPI 5) FL on 6/2006. He presented to us after failing to obtain a remission with 9 cycles of CVP+R (Cyclophosphamide, Vincristine, Prednisone, and Rituximab), followed by 6 cycles of FR (Fludarabine and Rituximab). After consultation with our service, he elected to be treated with BR (Bendamustine+Rituximab) in 8/2008 in preparation for allogeneic transplantation. He later opted to defer transplant, and died 3/2009, approximately 33 months from the time of diagnosis.

Case 2
Pt #2 was diagnosed with stage IVB/S (FLIPI 3) FL on 5/2006. He was initially treated with 2 cycles of CVP+R. Because of progressive disease during therapy, his regimen was changed to CHOP+R (Cyclophosphamide, Adriamycin, Vincristine, Prednisone, and Rituximab). Following his third cycle he was found to have hydronephrosis from progressive lymphadenopathy. A biopsy was obtained and revealed a transformation to diffuse large b-cell lymphoma. This occurred approximately 4 months from the time of diagnosis. He went on to receive 3 cycles of ESHAP+R (Etoposide, Methylprednisolone, Cytarabine, Cisplatin, and Rituximab), followed by 2 cycles of a regimen composed of Ifosfamide, Navelbine, Gemcitabine, and Rituximab, both without improvement. He was ultimately discharged to Hospice and died 3/2007, approximately 11 months from the time of diagnosis.
Clinical and pathologic features of these two cases at presentation are shown in Table 1.

Conclusion
In our case series, leukemic presentation in FL was associated with a poor response to therapy and limited survival. Interestingly, both patients demonstrated aberrant expression of CD5, and required further molecular characterization to rule out alternative diagnoses such as chronic lymphocytic leukemia and mantle cell lymphoma.
Although not uniformly seen in FL with lymphocytosis, small series in FL, as well as other lymphomas, suggest that lymphocytosis is more likely to occur with CD5 expression. An even smaller data set exists on outcomes in CD5 positive leukemic FL, with much of data similarly suggesting poor outcomes despite aggressive chemotherapy regimens and autologous stem cell transplant.

FL when accompanied by a brisk lymphocytosis and aberrant CD5 expression may herald a more aggressive disease. Whether similarly aggressive chemotherapy regimens and stem cell transplant can alter the dismal outcome in these patients has yet to be determined.

Disclosures
Off Label Use: Lenalidomide is an immune modulator drug currently being studied for efficacy in conjunction with Rituxan in chronic lymphocytic leukemia. This abstract summarizes a unique side effect, hypercalcemia, seen among a small cohort of patients on this study.