Elevated lactate dehydrogenase has prognostic relevance in treatment-naïve patients affected by chronic lymphocytic leukemia with trisomy 12

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number896
JournalCancers
Volume11
Issue number7
DOIs
Publication statusPublished - Jul 1 2019

Fingerprint

Trisomy
B-Cell Chronic Lymphocytic Leukemia
L-Lactate Dehydrogenase
Survival
Therapeutics
Disease-Free Survival
Immunoglobulin Heavy Chains
Fluorescence In Situ Hybridization
Disease Progression
Demography
Mortality

Keywords

  • CLL
  • LDH
  • Prognosis
  • Trisomy 12

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Elevated lactate dehydrogenase has prognostic relevance in treatment-naïve patients affected by chronic lymphocytic leukemia with trisomy 12. / Autore, Francesco; Strati, Paolo; Innocenti, Idanna; Corrente, Francesco; Trentin, Livio; Cortelezzi, Agostino; Visco, Carlo; Coscia, Marta; Cuneo, Antonio; Gozzetti, Alessandro; Mauro, Francesca Romana; Frustaci, Anna Maria; Gentile, Massimo; Morabito, Fortunato; Molica, Stefano; Falcucci, Paolo; D’Arena, Giovanni; Murru, Roberta; Vincelli, Donatella; Efremov, Dimitar G.; Ferretti, Antonietta; Rigolin, Gian Matteo; Vitale, Candida; Tisi, Maria Chiara; Reda, Gianluigi; Visentin, Andrea; Sica, Simona; Foà, Robin; Ferrajoli, Alessandra; Laurenti, Luca.

In: Cancers, Vol. 11, No. 7, 896, 01.07.2019.

Research output: Contribution to journalArticle

Autore, F, Strati, P, Innocenti, I, Corrente, F, Trentin, L, Cortelezzi, A, Visco, C, Coscia, M, Cuneo, A, Gozzetti, A, Mauro, FR, Frustaci, AM, Gentile, M, Morabito, F, Molica, S, Falcucci, P, D’Arena, G, Murru, R, Vincelli, D, Efremov, DG, Ferretti, A, Rigolin, GM, Vitale, C, Tisi, MC, Reda, G, Visentin, A, Sica, S, Foà, R, Ferrajoli, A & Laurenti, L 2019, 'Elevated lactate dehydrogenase has prognostic relevance in treatment-naïve patients affected by chronic lymphocytic leukemia with trisomy 12', Cancers, vol. 11, no. 7, 896. https://doi.org/10.3390/cancers11070896
Autore, Francesco ; Strati, Paolo ; Innocenti, Idanna ; Corrente, Francesco ; Trentin, Livio ; Cortelezzi, Agostino ; Visco, Carlo ; Coscia, Marta ; Cuneo, Antonio ; Gozzetti, Alessandro ; Mauro, Francesca Romana ; Frustaci, Anna Maria ; Gentile, Massimo ; Morabito, Fortunato ; Molica, Stefano ; Falcucci, Paolo ; D’Arena, Giovanni ; Murru, Roberta ; Vincelli, Donatella ; Efremov, Dimitar G. ; Ferretti, Antonietta ; Rigolin, Gian Matteo ; Vitale, Candida ; Tisi, Maria Chiara ; Reda, Gianluigi ; Visentin, Andrea ; Sica, Simona ; Foà, Robin ; Ferrajoli, Alessandra ; Laurenti, Luca. / Elevated lactate dehydrogenase has prognostic relevance in treatment-naïve patients affected by chronic lymphocytic leukemia with trisomy 12. In: Cancers. 2019 ; Vol. 11, No. 7.
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AU - Autore, Francesco

AU - Strati, Paolo

AU - Innocenti, Idanna

AU - Corrente, Francesco

AU - Trentin, Livio

AU - Cortelezzi, Agostino

AU - Visco, Carlo

AU - Coscia, Marta

AU - Cuneo, Antonio

AU - Gozzetti, Alessandro

AU - Mauro, Francesca Romana

AU - Frustaci, Anna Maria

AU - Gentile, Massimo

AU - Morabito, Fortunato

AU - Molica, Stefano

AU - Falcucci, Paolo

AU - D’Arena, Giovanni

AU - Murru, Roberta

AU - Vincelli, Donatella

AU - Efremov, Dimitar G.

AU - Ferretti, Antonietta

AU - Rigolin, Gian Matteo

AU - Vitale, Candida

AU - Tisi, Maria Chiara

AU - Reda, Gianluigi

AU - Visentin, Andrea

AU - Sica, Simona

AU - Foà, Robin

AU - Ferrajoli, Alessandra

AU - Laurenti, Luca

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N2 - 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.

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