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LDH AS PREDICTIVE PARAMETER IN TREATMENT-NAÏVE PATIENTS WITH TRISOMY 12 CHRONIC LYMPHOCYTIC LEUKEMIA
Author(s):
Francesco Autore
,
Francesco Autore
Affiliations:
Università Cattolica del Sacro Cuore, Fondazione Policlinico A. Gemelli,Rome,Italy
Paolo Strati
,
Paolo Strati
Affiliations:
MD Anderson Cancer Centre,Houston,United States
Idanna Innocenti
,
Idanna Innocenti
Affiliations:
Università Cattolica del Sacro Cuore, Fondazione Policlinico A. Gemelli,Rome,Italy
Francesco Corrente
,
Francesco Corrente
Affiliations:
Università Cattolica del Sacro Cuore, Fondazione Policlinico A. Gemelli,Rome,Italy
Livio Trentin
,
Livio Trentin
Affiliations:
Università di Padova,Padova,Italy
Agostino Cortelezzi
,
Agostino Cortelezzi
Affiliations:
IRCCS Ca’ Granda Policlinico - Università degli Studi,Milano,Italy
Carlo Visco
,
Carlo Visco
Affiliations:
Ospedale San Bortolo,Vicenza,Italy
Marta Coscia
,
Marta Coscia
Affiliations:
A.O. Città della Salute e della Scienza S. Giovanni Battista,Torino,Italy
Antonio Cuneo
,
Antonio Cuneo
Affiliations:
Azienda Ospedaliero Universitaria Arcispedale S. Anna,Ferrara,Italy
Alessandro Gozzetti
,
Alessandro Gozzetti
Affiliations:
Azienda Ospedaliera Universitaria Senese,Siena,Italy
Francesca Romana Mauro
,
Francesca Romana Mauro
Affiliations:
Università La Sapienza, Policlinico Umberto I,Rome,Italy
Marco Montillo
,
Marco Montillo
Affiliations:
Ospedale Niguarda,Milano,Italy
Massimo Gentile
,
Massimo Gentile
Affiliations:
Azienda Ospedaliera di Cosenza,Cosenza,Italy
Fortunato Morabito
,
Fortunato Morabito
Affiliations:
Azienda Ospedaliera di Cosenza,Cosenza,Italy
Stefano Molica
,
Stefano Molica
Affiliations:
Ospedale Pugliese - Ciacco,Catanzaro,Italy
Paolo Falcucci
,
Paolo Falcucci
Affiliations:
Ospedale Belcolle,Viterbo,Italy
Giovanni D'Arena
,
Giovanni D'Arena
Affiliations:
IRCCS Centro di Riferimento Oncologico della Basilicata,Rionero in Vulture,Italy
Roberta Murru
,
Roberta Murru
Affiliations:
Ospedale A. Businco,Cagliari,Italy
Donatella Vincelli
,
Donatella Vincelli
Affiliations:
Azienda Ospedaliera Bianchi-Melacrino-Morelli,Reggio Calabria,Italy
Piero Galieni
,
Piero Galieni
Affiliations:
Ospedale C. G. Mazzoni,Ascoli Piceno,Italy
Gianluigi Reda
,
Gianluigi Reda
Affiliations:
IRCCS Ca’ Granda Policlinico - Università degli Studi,Milano,Italy
Maria Chiara Tisi
,
Maria Chiara Tisi
Affiliations:
Ospedale San Bortolo,Vicenza,Italy
Candida Vitale
,
Candida Vitale
Affiliations:
A.O. Città della Salute e della Scienza S. Giovanni Battista,Torino,Italy
Gian Matteo Rigolin
,
Gian Matteo Rigolin
Affiliations:
Azienda Ospedaliero Universitaria Arcispedale S. Anna,Ferrara,Italy
Alessandra Ferrajoli
,
Alessandra Ferrajoli
Affiliations:
MD Anderson Cancer Centre,Houston,United States
Luca Laurenti
Luca Laurenti
Affiliations:
Università Cattolica del Sacro Cuore, Fondazione Policlinico A. Gemelli,Rome,Italy
(Abstract release date: 05/18/17) EHA Library. Autore F. 05/18/17; 182474; PB1760
Dr. Francesco Autore
Dr. Francesco Autore
Contributions
PDF Abstract
Abstract

Abstract: PB1760

Type: Publication Only

Background
Patients affected by chronic lymphocytic leukemia (CLL) that have trisomy 12 (+12) on FISH analysis have unique clinical and biological features. In a prior analysis (Autore F, ASH 2016) of 487 patients with +12 compared to 816 patients with negative FISH, patients with +12 had a significantly higher prevalence of elevated LDH, β-2-microglobulin, ZAP70 positivity, CD38 positivity, CD49d positivity and unmutated IGHV as compared to patients with negative FISH. They also showed shorter progression free survival (PFS), treatment free survival (TFS) and overall survival (OS).

Aims
To identify clinical and laboratory features that predict disease progression, time to treatment and survival in treatment-naive patients with +12 CLL.

Methods

This study included 487 treatment-naive patients with +12 CLL from 16 academic centres, diagnosed between January 2000 and July 2016. A cohort of 250 patients with +12 CLL followed at a single US institution was used as external validation. Data were summarized as medians and 25th and 75th percentiles. Chi-square test or Fisher’s exact test were used to compare categorical variables, while Wilcoxon-Mann-Whitney-Test was applied for continuous variables. The survival analysis was based on the Kaplan-Meier method and the log-rank test was used to compare survival curves. A Cox model was used for multivariate analysis of the impact of different factors on survival. P values lower than 0.05 were considered statistically significant (STATA 12.0) and reported as two-sided. We analysed also CLL-specific survival considering events deaths due to the haematological disease.

Results

Parameters associated with shorter PFS, TFS, OS and CLL-specific survival on univariate analysis were IGHV, LDH, β-2-microglobulin and Rai stage; age, ZAP70 and CD38 associated with OS only; on multivariate analysis, high LDH and unmutated IGHV remained significantly with shorter PFS, TFS, OS and CLL-specific survival, higher Rai stage with shorter PFS and elevated β-2-microglobulin with shorter OS.
Considering interestingly the association of a simple and new laboratory parameter such as LDH to the outcomes, confirmed on multivariate analyses for PFS (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.2 to 2.1; p=0.004), TFS (HR 1.62, 95% CI 1.2-2.2; p=0.002), OS (HR 1.69, 95% CI 1.1-2.7; p=0.034) and CLL-specific survival (HR 3.86, 95% CI 2.0-7.5; p<0.001), we divided our +12 CLL cohort according to LDH levels available at diagnosis: 103 patients showed LDH levels above the normal limit and 184 within normal range. Patients with high LDH levels showed shorter PFS (30 months vs 65 months, p<0.001; Figure 1A), TFS (33 months vs 69 months, p<0.001; Figure 1B), OS (131 months vs 181 months, p<0.001; Figure 1C) and CLL-specific survival with a rate of attributable mortality of 29% vs. 11% (p<0.001).
In the validation cohort, 104 patients had high LDH levels and 145 patients had normal LDH levels; factors significantly associated with PFS and TFS on univariate analysis were LDH, β-2-microglobulin, Rai stage and ZAP70; LDH, β-2-microglobulin and age associated with OS. On multivariate analysis high LDH was the sole parameter significantly associated with all shorter outcomes, along with elevated β-2-microglobulin, which associated with shorter OS.

Conclusion
Our study on 487 patients with +12 CLL and the analysis on 250 patients of the validation cohort showed that patients with +12 and elevated LDH have shorter PFS, TFS, OS and CLL-specific survival.

Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology

Keyword(s): Prognostic factor, FISH, Chronic Lymphocytic Leukemia

Abstract: PB1760

Type: Publication Only

Background
Patients affected by chronic lymphocytic leukemia (CLL) that have trisomy 12 (+12) on FISH analysis have unique clinical and biological features. In a prior analysis (Autore F, ASH 2016) of 487 patients with +12 compared to 816 patients with negative FISH, patients with +12 had a significantly higher prevalence of elevated LDH, β-2-microglobulin, ZAP70 positivity, CD38 positivity, CD49d positivity and unmutated IGHV as compared to patients with negative FISH. They also showed shorter progression free survival (PFS), treatment free survival (TFS) and overall survival (OS).

Aims
To identify clinical and laboratory features that predict disease progression, time to treatment and survival in treatment-naive patients with +12 CLL.

Methods

This study included 487 treatment-naive patients with +12 CLL from 16 academic centres, diagnosed between January 2000 and July 2016. A cohort of 250 patients with +12 CLL followed at a single US institution was used as external validation. Data were summarized as medians and 25th and 75th percentiles. Chi-square test or Fisher’s exact test were used to compare categorical variables, while Wilcoxon-Mann-Whitney-Test was applied for continuous variables. The survival analysis was based on the Kaplan-Meier method and the log-rank test was used to compare survival curves. A Cox model was used for multivariate analysis of the impact of different factors on survival. P values lower than 0.05 were considered statistically significant (STATA 12.0) and reported as two-sided. We analysed also CLL-specific survival considering events deaths due to the haematological disease.

Results

Parameters associated with shorter PFS, TFS, OS and CLL-specific survival on univariate analysis were IGHV, LDH, β-2-microglobulin and Rai stage; age, ZAP70 and CD38 associated with OS only; on multivariate analysis, high LDH and unmutated IGHV remained significantly with shorter PFS, TFS, OS and CLL-specific survival, higher Rai stage with shorter PFS and elevated β-2-microglobulin with shorter OS.
Considering interestingly the association of a simple and new laboratory parameter such as LDH to the outcomes, confirmed on multivariate analyses for PFS (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.2 to 2.1; p=0.004), TFS (HR 1.62, 95% CI 1.2-2.2; p=0.002), OS (HR 1.69, 95% CI 1.1-2.7; p=0.034) and CLL-specific survival (HR 3.86, 95% CI 2.0-7.5; p<0.001), we divided our +12 CLL cohort according to LDH levels available at diagnosis: 103 patients showed LDH levels above the normal limit and 184 within normal range. Patients with high LDH levels showed shorter PFS (30 months vs 65 months, p<0.001; Figure 1A), TFS (33 months vs 69 months, p<0.001; Figure 1B), OS (131 months vs 181 months, p<0.001; Figure 1C) and CLL-specific survival with a rate of attributable mortality of 29% vs. 11% (p<0.001).
In the validation cohort, 104 patients had high LDH levels and 145 patients had normal LDH levels; factors significantly associated with PFS and TFS on univariate analysis were LDH, β-2-microglobulin, Rai stage and ZAP70; LDH, β-2-microglobulin and age associated with OS. On multivariate analysis high LDH was the sole parameter significantly associated with all shorter outcomes, along with elevated β-2-microglobulin, which associated with shorter OS.

Conclusion
Our study on 487 patients with +12 CLL and the analysis on 250 patients of the validation cohort showed that patients with +12 and elevated LDH have shorter PFS, TFS, OS and CLL-specific survival.

Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology

Keyword(s): Prognostic factor, FISH, Chronic Lymphocytic Leukemia

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