Definition of progression risk based on combinations of cellular and molecular markers in patients with Binet stage A chronic lymphocytic leukaemia |
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| Authors: | Fortunato Morabito Giovanna Cutrona Massimo Gentile Serena Matis Katia Todoerti Monica Colombo Claudia Sonaglio Sonia Fabris Daniele Reverberi Mauro Megna Mauro Spriano Eugenio Lucia Edoardo Rossi Vincenzo Callea Carla Mazzone Gianluca Festini Simonetta Zupo Stefano Molica Antonino Neri Manlio Ferrarini |
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| Affiliation: | UnitàOperativa Complessa di Ematologia, Azienda Ospedaliera, Cosenza;, Divisione di Oncologia Medica C, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova;, Centro di Ricerca per lo Studio delle Leucemie, Dipartimento di Scienze Mediche, Universitàdi Milano, U.O. Ematologia 1, Fondazione IRCCS Policlinico, Milano;, Divisione di Diagnostica delle Malattie Linfoproliferative, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova;, Dipartimento di Ematologia, Azienda Ospedaliera S. Martino, Genova;, Divisione di Ematologia, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria;, Divisione di Ematologia, Ospedale Maggiore Trieste, Trieste;, Dipartimento di Oncologia/Ematologia, Azienda Ospedaliera Pugliese-Ciaccio, Catanzaro;, and Dipartimento di Oncologia, Biologia e Genetica Universitàdegli Studi di Genova, Italy |
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| Abstract: | IGHV mutational status and ZAP-70 or CD38 expression correlate with clinical course in B-cell chronic lymphocytic leukaemia (CLL). The three markers may be discordant in the single case and there is no consensus on their combined use in clinical practise. This multicenter study investigated this issue. Two-hundred and sixty-two Binet stage A patients were studied for the three markers. Sixty patients were profiled with HG-U133A gene expression chips. Disease progression was determined by time from diagnosis to treatment (TTT). The probability of being treatment-free at 3 years was significantly shorter in patients with unmutated IGHV genes ( IGHV unmut 66% vs. 93%, chi square of log-rank = 30, P < 0·0001), ZAP-70 positive (ZAP-70pos 73% vs. 96%, chi square of log-rank = 8·2, P = 0·004) or CD38-positive cells (CD38pos 68% vs. 91%, chi square of log-rank = 21, P < 0·0001). Cox multivariate regression analysis showed that the three markers had an independent predictive value for TTT of similar power. A prognostic system based on presence of none (low-risk), one (intermediate-risk) or two or three (high-risk) markers was generated. Based on such criteria, 56%, 23% and 21% of cases were clustered in low (HR = 1), intermediate [HR = 2·8, 95% confidence interval (CI) 2·4–5·8] and high-risk group (HR = 8·0, 95% CI 3·9–16·2). Specific transcriptional patterns were significantly associated with risk groups. |
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| Keywords: | chronic lymphocytic leukaemia gene expression profiling ZAP-70 CD38 IGHV mutational status |
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