Elevated Lactate Dehydrogenase Has Prognostic Relevance in Treatment-Naïve Patients Affected by Chronic Lymphocytic Leukemia with Trisomy 12.

Francesco Autore ,Candida Vitale ,Livio Trentin ,Antonio Cuneo ,Anna Maria Frustaci ,Gianluigi Reda ,Marta Coscia ,Donatella Vincelli ,Alessandro Gozzetti ,Massimo Gentile ,Gian Matteo Rigolin ,Paolo Strati ,Alessandra Ferrajoli ,Carlo Visco ,Dimitar G Efremov ,Giovanni D’arena ,Simona Sica ,Stefano Molica ,Agostino Cortelezzi ,Andrea Visentin ,Fortunato Morabito ,Francesco Corrente ,Roberta Murru ,Paolo Falcucci ,Maria Chiara Tisi ,Robin Foà ,Idanna Innocenti ,Antonietta Ferretti ,Francesca Romana Mauro ,Luca Laurenti

doi:10.3390/cancers11070896

Abstract

Chronic Lymphocytic Leukemia (CLL) patients with +12 have been reported to have specific clinical and biologic features. We performed an analysis of the association between demographic; clinical; laboratory; biologic features and outcome in CLL patients with +12 to identify parameters predictive of disease progression; time to treatment; and survival. The study included 487 treatment-naive CLL patients with +12 from 15 academic centers; diagnosed between January 2000 and July 2016; and 816 treatment-naïve patients with absence of Fluorescence In Situ Hybridization (FISH) abnormalities. A cohort of 250 patients with +12 CLL followed at a single US institution was used for external validation. In patients with +12; parameters associated with worse prognosis in the multivariate model were high Lactate DeHydrogenase (LDH) and β-2-microglobulin and unmutated immunoglobulin heavy-chain variable region gene (IGHV). CLL patients with +12 and high LDH levels showed a shorter Progression-Free-Survival (PFS) (30 months vs. 65 months; p < 0.001), Treatment-Free-Survival (TFS) (33 months vs. 69 months; p < 0.001), Overall Survival (OS) (131 months vs. 181 months; p < 0.001) and greater CLL-related mortality (29% vs. 11% at 10 years; p < 0.001) when compared with +12 CLL patients with normal LDH levels. The same differences were observed in the validation cohort. These data suggest that serum LDH levels can predict PFS; TFS; OS and CLL-specific survival in CLL patients with +12.

Highlights

The clinical course of chronic lymphocytic leukemia (CLL) is very heterogeneous and the identification of prognostic and predictive factors for Chronic Lymphocytic Leukemia (CLL) is of great relevance and a field of active investigation [1,2]
We present a large series of treatment-naive +12 CLL patients and correlate the association between demographic, clinical, laboratory, and biologic features and clinical outcomes
Negative fluorescence in situ hybridization (FISH) patients had a median age at diagnosis of 63.0 years and a male/female M:F ratio of 1.58 (500 males, 61%; and 316 females, 39%)

Summary

Introduction

The clinical course of chronic lymphocytic leukemia (CLL) is very heterogeneous and the identification of prognostic and predictive factors for CLL is of great relevance and a field of active investigation [1,2]. The analysis of aberrant chromosomal regions with specific DNA probes by fluorescence in situ hybridization (FISH) resulted in the detection of clonal aberrations and the main recurrent chromosomal abnormalities (del13q, +12, del11q and del17p) define different personal genetic profiling subgroups in CLL [7,8]. Trisomy 12 is the second most frequent cytogenetic abnormality identified by FISH in patients with CLL [7]. It presents as an isolated aberration in about 70% of cases and when it is associated with additional chromosomal abnormalities portends a poor prognosis [7,8,9,10,11].

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