Genomic aberrations and survival in chronic lymphocytic leukemia.

Background: Fluorescence in situ hybridization has improved the detection o f genomic aberrations in chronic lymphocytic leukemia. We used this method to identify chromosomal abnormalities in patients with chronic lymphocytic leukemia and assessed their prognostic implications. Methods: Mononuclear cells from the blood of 325 patients with chronic lymp hocytic leukemia were analyzed by fluorescence in situ hybridization for de letions in chromosome bands 6q21, 11q22-23, 13q14, and 17p13; trisomy of ba nds 3q26, 8q24, and 12q13; and translocations involving band 14q32. Molecul ar cytogenetic data were correlated with clinical findings. Results: Chromosomal aberrations were detected in 268 of 325 cases (82 perc ent). The most frequent changes were a deletion in 13q (55 percent), a dele tion in 11q (18 percent), trisomy of 12q (16 percent), a deletion in 17p (7 percent), and a deletion in 6q (6 percent). Five categories were defined w ith a statistical model: 17p deletion, 11q deletion, 12q trisomy, normal ka ryotype, and 13q deletion as the sole abnormality; the median survival time s for patients in these groups were 32, 79, 114, 111, and 133 months, respe ctively. Patients in the 17p- and 11q-deletion groups had more advanced dis ease than those in the other three groups. Patients with 17p deletions had the shortest median treatment-free interval (9 months), and those with 13q deletions had the longest (92 months). In multivariate analysis, the presen ce or absence of a 17p deletion, the presence or absence of an 11q deletion , age, Binet stage, the serum lactate dehydrogenase level, and the white-ce ll count gave significant prognostic information. Conclusions: Genomic aberrations in chronic lymphocytic leukemia are import ant independent predictors of disease progression and survival. These findi ngs have implications for the design of risk-adapted treatment strategies. (N Engl J Med 2000;343:1910-6.) (C) 2000, Massachusetts Medical Society.