TY - JOUR
T1 - Definition of progression risk based on combinations of cellular and molecular markers in patients with Binet stage A chronic lymphocytic leukaemia
AU - Morabito, Fortunato
AU - Cutrona, Giovanna
AU - Gentile, Massimo
AU - Matis, Serena
AU - Todoerti, Katia
AU - Colombo, Monica
AU - Sonaglio, Claudia
AU - Fabris, Sonia
AU - Reverberi, Daniele
AU - Megna, Mauro
AU - Spriano, Mauro
AU - Lucia, Eugenio
AU - Rossi, Edoardo
AU - Callea, Vincenzo
AU - Mazzone, Carla
AU - Festini, Gianluca
AU - Zupo, Simonetta
AU - Molica, Stefano
AU - Neri, Antonino
AU - Ferrarini, Manlio
PY - 2009/7
Y1 - 2009/7
N2 - 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 (IGHVunmut 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.
AB - 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 (IGHVunmut 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.
KW - CD38
KW - Chronic lymphocytic leukaemia
KW - Gene expression profiling
KW - IGHV mutational status
KW - ZAP-70
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U2 - 10.1111/j.1365-2141.2009.07703.x
DO - 10.1111/j.1365-2141.2009.07703.x
M3 - Article
C2 - 19438486
AN - SCOPUS:66949121753
VL - 146
SP - 44
EP - 53
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 1
ER -