Comparison of Small Lymphocytic Lymphoma with Chronic Lymphocytic Leukemia The M.D Anderson Cancer Center Experience.

Introduction: Small lymphocytic lymphoma (SLL) and chronic lymphocytic leukemia (CLL) are viewed as similar entities by the World Health Organization. Patients with SLL are usually treated on protocols for indolent lymphomas, although the biology of SLL differs from that of follicular lymphomas. The purpose of this study was to assess differences, if any, in presenting characteristics, cytogenetics, treatment outcomes, and factors predicting survival between patients with CLL and those with absolute lymphocyte counts <5,000 (SLL).

Methods: An electronic database search of patients with CLL/SLL who presented at The University of Texas M.D. Anderson Cancer Center Department of Leukemia between 1985 and 2005 was performed.

Results: Among 2,051 patients with untreated CLL/SLL, 199 patients had SLL and 1852 patients had CLL. Patients with SLL were referred for node enlargement (33%), coincidental abnormal white blood cell counts (27%), fatigue (11%), B-symptoms (10%), bruising/low platelets (8%), surgical specimens (8%), and other reasons (8%). In univariate analysis, patients with SLL had higher hemoglobin levels (p<0.001), lower IgA and IgM immunoglobulin levels (p=0.03 and p=0.01, respectively), and lower rates of bone marrow lymphocytic infiltration (p<0.001) than those with CLL. Age, sex, Binet stage, and β₂-microglobulin levels were similar between the two groups. Fluorescence in situ hybridization (FISH) abnormalities were more frequent in tested patients with CLL compared with SLL patients (70% and 45%, respectively). Among 40 SLL patients with FISH abnormalities, 18% had 11q-, 25% had trisomy 12, 33% had 13q-, and 5% had 17p- abnormalities. Among 314 CLL patients with FISH abnormalities, 14% had 11q-, 16% had trisomy 12, 51% had 13q-, and 5% had 17p- abnormalities. Forty percent of patients with SLL and 49% of CLL patients required therapy after a median follow-up of 5.8 and 3.0 years, respectively (p<0.001). Among evaluable patients (SLL, 32; CLL, 710), the overall response rates to various therapies were 78% (CR, 41%) and 88% (CR, 48%), respectively. Responses were more frequent among SLL patients treated with fludarabine, mitoxantrone, and dexamethasone (FND), FND with rituximab (R-FND) or fludarabine, cyclophosphamide, and rituximab (FCR) and among patients with CLL treated with FCR. In multivariate analysis of all 2,051 SLL/CLL patients, factors predicting longer survival were younger age (p<0.0001), lower β₂-microglobulin levels (p<0.0001), lower alkaline phosphatase levels (p<0.0001), higher hemoglobin levels (p<0.0001), smaller number of nodal sites (p<0.001), and lower lactate dehydrogenase levels (p=0.01); the absolute lymphocyte count was not a significant factor in survival (p=0.30).

Conclusions: The presentation, cytogenetic abnormalities, and clinical outcome of SLL are similar but not identical to those of CLL. Our results suggest that SLL and CLL can be treated similarly. Regimens that include rituximab and a nucleoside analog, such as FCR or R-FND, are highly effective. Further characterization of SLL by genetic analysis is needed. Common response criteria should be standardized for both CLL and SLL, including the disappearance of radiologic and hematologic evidence of disease.