Acquired Silent Cytogenetic Clones Arising in Patients Treated Successfully for Lymphoma
Gary Lu, C Cameron Yin, Lynne V Abruzzo, Raja Luthra, Ronald Abraham, Rashmi Kanagal-Shamanna, L Jeffrey Medeiros. University of Texas MD Anderson Cancer Center, Houston, TX
Background: Cytotoxic effects of therapeutic agents can result in acquisition of abnormal cytogenetic clones during the course of therapy in cancer patients, eventually resulting in therapy-related myeloid neoplasms. However, the features of acquired silent cytogenetic clones (ASCC) after therapy and their clinicopathologic significance are not well characterized.
Design: The database at MD Anderson Cancer Center was searched from 02/2009 to 03/2012 for patients treated successfully for lymphoma who developed acquired cytogenetic abnormalities. Cases with silent clones were selected for clinicopathologic analysis. Criteria to define ASCC included: (1) clonality confirmed by karyotyping and/or FISH; (2) no evidence of myeloid disease confirmed by bone marrow (BM) morphologic evaluation; and (3) no clinical manifestations of secondary disease. We performed array CGH using an Agilent platform on cases with available DNA to assess the silent clones.
Results: We identified 15 patients treated for lymphoma who then developed ASCC. Patients (9 men, 6 women) were 35-79 years (median, 65) of age. The lymphomas in these patients were: follicular lymphoma (n=8), marginal zone B-cell lymphoma (n=2), mantle cell lymphoma (n=2), diffuse large B-cell lymphoma (n=1), anaplastic large cell lymphoma (n=1), and Hodgkin lymphoma (n=1). Clonal abnormalities identified in a median of 2 metaphases included: -7/del(7q) (n=7), del(20q) (n=3), -5/del(5q) (n=2), -5/del(7q) (n=1), del(13q) (n=1), and +15 (n=1). The interval from therapy to initial ASCC detection was 70 months (ranged 12-300). In 14 cases with data available, repeated BM morphologic evaluation revealed a normal blast count, and was considered normal (n=9), mild dyspoiesis (n=3), and suspicious for MDS (n=2). For 10 patients with follow up of a median interval of 32 months (range, 24-60), 9 patients were alive without disease and 1 developed to therapy-related MDS after 24 months. ASCC was detectable in 1 of the 3 cases by aCGH.
Conclusions: The results from this cohort showed: (1) ASCC can be detected at a low percentage of metaphase/interphase by conventional cytogenetics or FISH after a latency interval of approximately 6 years; but detectable in a small subset of the cases by aCGH; (2) the most common ASCC abnormalities are -7/del(7q), -5/del(5q) and del(20q); (3) only a small subset of these patients went on to therapy-related MDS in the follow-up period.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 223, Wednesday Morning