Immunoglobulin heavy chain (IGH@) translocations negatively impact treatment-free survival for chronic lymphocytic leukemia patients who have an isolated deletion 13q abnormality

Immunoglobulin heavy chain translocations (t( IGH@ )) are suggested to portend a poor prognosis in chronic lymphocytic leukemia (CLL). To determine the clinical significance of a t( IGH@ ) on CLL-specific cytogenetic abnormalities, we analyzed the outcomes of 142 CLL patients referred for fluorescence in situ hybridization (FISH) analysis with our standard FISH panel, which includes testing for a t( IGH@ ). Whereas patients with unfavorable (deletion 17p, deletion 11q) and intermediate (trisomy 12, normal FISH) cytogenetics with concomitant t( IGH@ ) had similar median treatment-free survival (TFS) as those without a t( IGH@ ), patients with deletion 13q (del13q) and a t( IGH@ ) had significantly worse TFS than those without a t( IGH@ ): median TFS 4.7 versus 8.0 years, P = 0.03 (hazard ratio 4.21, 95% confidence interval 1.06–16.69 y, P = 0.04 in multivariate analysis after adjusting for age, sex, Rai stage, and white blood cell count). The presence of a t( IGH@ ) further stratified patients with del13q into two prognostic entities, whereby outcomes of those with coexistent del13q and a t( IGH@ ) were similar to outcomes of those with high risk cytogenetics. Knowledge of the t( IGH@ ) status in CLL is therefore of clinical importance, as del13q patients with concomitant t( IGH@ ) may not retain the previously expected favorable outcome.