Chronic Lymphocytic Leukemia Associated with t(14;18)(q32;q21)
Guilin Tang, Rachel L Sargent, Jeffrey L Medeiros, Lynne V Abruzzo. UT MD Anderson Cancer Center, Houston, TX
Background: The t(14;18)(q32;q21) involving IGH and BCL2 is most commonly associated with lymphomas of follicle center cell origin. It has been identified in ∼90% of follicular lymphomas and ∼25% of diffuse large B-cell lymphomas. In chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), however, the t(14;18) is unusual. We report the clinical, morphologic, immunophenotypic, cytogenetic, and molecular genetic features of 12 cases of CLL associated with t(14;18).
Design: We searched our database from 1996-2011 and identified 12 CLL cases associated with t(14;18)(q32;q21). We retrieved clinicopathological data, immunophenotype and cytogenetics from the medical records. We performed fluorescence in situ hybridization (FISH) analysis for IGH/BCL-2 rearrangement using a dual-color dual-fusion probe. Analysis of the IGHV somatic mutation status was performed on blood or bone marrow clot.
Results: The study group included 9 men and 3 women with a median age of 54 years (range: 45-78). At the time of presentation to our institution, 11 patients had lymphocytosis, 7 had anemia, and 8 had thrombocytopenia. All patients had bone marrow involvement, 7 had lymphadenopathy, and 4 had hepatosplenomegaly. Nine patients had received prior therapy for CLL. Four cases showed atypical lymphocyte morphology with clefted or irregular nuclear contour, or plasmacytoid differentiation; one case had increased prolymphocytes (≥15%). Flow cytometry showed that 7 cases had typical and 5 had atypical immunophenotypes. Karyotypic analysis showed that 10 cases had t(14;18) in the stemline and 2 cases in the sideline. The t(14;18) was the sole abnormality in the stemline in 2 cases. In 11 cases, other abnormalities either in the stemline or sideline were identified, most commonly +12 (6 cases), which was associated with atypical morphology and immunophenotype. In 10 cases with available material, IGH/BCL2 rearrangement was confirmed by FISH analysis (9 cases) or PCR assay (1 case). In 8 cases assessed 7 showed somatically mutated IGHV genes (6 ZAP70 negative, 1 positive) and 1 was unmutated (ZAP70 positive). With a median follow-up of 8 years (0-29 years), 5 patients died of disease (2 with Richter transformation) and 7 patients are alive (6 with persistent CLL, and 1 in remission), with a median survival of 10 years.
Conclusions: The t(14;18) in CLL is associated with younger age at diagnosis, mutated IGHV genes, and a relatively shorter median survival. The finding of t(14;18) as the sole abnormality in the stemline of 2 cases raises the possibility that the t(14;18) may be an early pathogenetic event in a subset of cases.
Monday, March 19, 2012 1:00 PM
Poster Session II # 202, Monday Afternoon