Affiliations: [a] Niguarda Cà Granda Hospital, Division of Hematology, Milan, Italy | [b] Niguarda Cà Granda Hospital, Service of Biostatistics, Milan, Italy | [c] Niguarda Cà Granda Hospital, Molecular Pathology Unit, Department of Laboratory Medicine, Milan, Italy | [d] Niguarda Cà Granda Hospital, Pathological Anatomy and Cytogenetics, Department of Laboratory Medicine, Milan, Italy | [e] Niguarda Cà Granda Hospital, Department of Trasfusion Medicine and Division of Hematology, Milan, Italy
Correspondence:
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Corresponding author: Dr. Alessandra Trojani, Niguarda Ca' Granda Hospital, Division of Hematology, Piazza Ospedale Maggiore, 3, Milan 20162, Italy. Tel.: +39 2 64442740; Fax: +39 2 64444089; E-mail: alessandra.trojani@ospedaleniguarda.it.
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.
