Abstract
AbstractAbstract 2009Lymphoplasmacytic lymphoma (LPL) belongs to the most frequently occurring mature B-cell neoplasms besides chronic lymphocytic leukemia, splenic marginal zone lymphoma (SMZL), mantle cell lymphoma, follicular lymphoma, and hairy cell leukemia. Data on cytogenetic abnormalities in LPL is limited although these may facilitate the differentiation between LPL and other mature B-cell neoplasms with similar immunophenotypic features like SMZL. Thus, cytogenetic analysis may be a valuable tool to better characterize these cases and may in addition give prognostic information. We therefore analyzed bone marrow samples from 166 patients with LPL in parallel by cytomorphology, multiparameter flow cytometry (MFC) and chromosome banding analysis (CBA). In addition, fluorescence in situ hybridization (FISH) analysis was performed in 98/166 patients applying a standard panel of probes targeting del(6q), del(11q22.3) (ATM), trisomy 12, del(13q14) (D13S25, D13S319), and del(17p13) (TP53). The patients′ ages ranged from 40.9 to 87.2 years (median, 68.5 years), the male/female ratio was 1.18:1.00. The median percentage of LPL cells detected in bone samples by MFC amounted to 8% (range, 0.4% to 79%). In 66 patients (39.8%) an aberrant karyotype was identified by CBA. Specifically, these aberrations were classified into the following categories: complex karyotype (defined as at least three structural or numeric aberrations), 7.8%; loss of Y chromosome, 5.4%; del(5q), 1.2%; trisomies, 7.2%; other deletions, 3.6%; translocations, 1.8%; and other aberrations, 12.6%. FISH analysis identified the following chromosomal aberrations: del(6q), 3/60 (5.0%); del(11q22.3), 2/84 (2.4%); trisomy 12, 7/75 (9.3%); del(13q14), 13/98 (13.3%); and del(17p13), 7/85 (8.2%). Patients with aberrant karyotypes as identified by CBA were older than other patients (mean±SD, 70.0±9.0 vs. 65.7±10.4, p=0.007), and they had a significantly higher percentage of lymphoma cells as identified by MFC (mean±SD, 23.1±21.4% vs. 11.3±12.5%, p<0.001). Cases in which FISH analysis identified a del(13q) had a higher percentage of lymphoma cells as identified by MFC as compared to those without del(13q) (31.2±21.7% vs. 16.0±17.0%, p=0.005). The same was true for cases with del(17p) (40.9±25.3% vs. 14.2±14.6%, p=0.031). There were no significant differences in the percentage of lymphoma cells as identified by MFC for cases with the other chromosomal aberrations detected by FISH analysis. This data suggests that chromosomal aberrations can be detected in bone marrow samples infiltrated by LPL in 40% of the cases. Since in patients with chromosomal aberrations higher degrees of bone marrow infiltration by lymphoma cells were found it is suggested that CBA may miss chromosomal aberrations in cases with a lower degree (<5%) of bone marrow infiltration. For FISH analysis similar observations were made, i.e. a higher degree of bone marrow infiltration in cases with del(13q) or del(17p). This may indicate a more aggressive clinical course of LPL in the presence of these chromosomal aberrations. Furthermore, taking into consideration the level of sensitivity level of FISH analysis (1% to 3%) this data suggests the absence of chromosomal aberrations in cases with a lower degree of bone marrow infiltration rather than the lack of their detection by CBA and FISH analysis. With regard to the potential clinical implications of chromosomal aberrations, i.e. the estimation of the clinical course of the disease and of the patient′s prognosis, CBA and FISH analysis should be considered for routine diagnostic work-up in patients with LPL and bone marrow infiltration as detected by MFC. Disclosures:Kern: MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Schnittger:MLL Munich Leukemia Laboratory: Employment, Equity Ownership. Haferlach:MLL Munich Leukemia Laboratory: Employment, Equity Ownership.
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