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Definition of progression risk based on combinations of cellular and molecular markers in patients with Binet stage A chronic lymphocytic leukaemia
Author(s) -
Morabito Fortunato,
Cutrona Giovanna,
Gentile Massimo,
Matis Serena,
Todoerti Katia,
Colombo Monica,
Sonaglio Claudia,
Fabris Sonia,
Reverberi Daniele,
Megna Mauro,
Spriano Mauro,
Lucia Eugenio,
Rossi Edoardo,
Callea Vincenzo,
Mazzone Carla,
Festini Gianluca,
Zupo Simonetta,
Molica Stefano,
Neri Antonino,
Ferrarini Manlio
Publication year - 2009
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2009.07703.x
Subject(s) - ighv@ , cd38 , medicine , stage (stratigraphy) , confidence interval , proportional hazards model , oncology , gastroenterology , logistic regression , chronic lymphocytic leukemia , biology , leukemia , genetics , paleontology , stem cell , cd34
Summary 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.