Abstract
Introduction: Genomic aberrations provide information for the pathogenesis and clinical outcomes of patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). We assessed whether genomic aberrations in CLL/SLL differ by absolute lymphocyte count (ALC) and evaluated their prognostic significance in our series of patients with CLL/SLL.
Methods: We reviewed the medical records of patients with CLL/SLL who presented to The University of Texas M. D. Anderson Cancer Center from 1985 to 2005. Patients were assessed by conventional bone marrow cytogenetics and/or fluorescence in situ hybridization (FISH) analysis using probes for trisomy 12, ATM, LAMP1, D13S319, and P53 genes.
Results: Cytogenetics and/or FISH analysis was performed in 1694 of 2189 consecutive patients with CLL/SLL. Patients with ALC < 5 × 109/L had lower rates of genomic aberrations by cytogenetic and/or FISH analysis than did those with ALC ≥ 5 × 109/L (25% vs. 37%, p=0.02). Deletion 17p +/− other abnormalities and 6q del +/− other abnormalities were each associated with shorter survival compared with other genomic aberrations or normal karyotype (p<0.0001 for both results). The survival rates by genomic aberration are shown in the Figure [insert figure here]. In a multivariate analysis of 23 clinical and laboratory factors, deletion 17p or 6q +/− other genomic aberrations (p<0.0001) was the strongest independent predictor of shorter survival. In patients who required therapy for CLL/SLL, independent factors predicting response were hemoglobin levels > 11 g/dL (p<0.0001), age < 60 years (p=0.005), absence of 17p deletion (p=0.048), and absence of 6q deletion (p=0.03). In multivariate analysis, pretreatment parameters that remained independently significant for longer failure-free survival (FFS) were age < 60 years (p<0.0001), absence of 17p del +/− other abnormalities (p<0.0001), and hemoglobin levels > 11 g/dL (p=0.018).
Conclusions: Patients with CLL/SLL and ALC < 5 × 109/L had lower rates of genomic aberrations by cytogenetic and/or FISH analysis (p=0.02), possibly because of less bone marrow infiltration in the lower-ALC group. Deletion 17p or 6q, with or without other genomic aberrations was the strongest independent adverse prognostic factor for survival in CLL/SLL.
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Disclosure: No relevant conflicts of interest to declare.
