ZAP-70, IgVh, and cytogenetics for assessing prognosis in chronic lymphocytic leukemia.

ABSTRACT

BACKGROUND: New prognostic factors such as IgVh mutational status, ZAP-70 protein expression and cytogenetic abnormalities have shown to offer important prognostic information for patients with chronic lymphocytic leukemia (CLL). Our aim was to evaluate the optimal cut-off for IgVh mutational status, ZAP-70 expression and cytogenetic abnormalities in association with disease progression defined as the need for treatment within 3~years from diagnosis in 170 patients with B-CLL. DESIGN AND METHODS: Receiver operating characteristics (ROC) analysis and multivariate general linear models (GLMs) were used to investigate the most significant cut-off values of these biomarkers and their prognostic impact. RESULTS: Our findings estimated that the optimal cut-off for IgVh mutation status and for ZAP-70 protein expression was 97% and 16.5% respectively and a high concordance between the two was demonstrated. We identified 30% as being the best-cut-off for 17p-, 11q- and 6q-. In univariate analysis 17p- was found to be a significant predictor of the event only for the whole population. Multivariate analysis including all biological parameters, identified 11q deletion as the only significant regressor. CONCLUSIONS: We assessed that IgVh mutational status, ZAP-70 protein and 6q- are powerful prognostic markers. Analyses of all these factors revealed that 11q deletion was the strongest predictor of disease progression in B-CLL.