A risk score based on three biological features (CD38, ZAP-70, and IGHV mutational status) was previously developed to predict progression-free survival (PFS) in untreated Binet A CLL patients. Here we perform a score validation analysis in a prospective and independent cohort of patients. Biological markers (CD38, ZAP-70, and IGHV mutational status) and gene expression profiles (GEP) of leukemic cells from CLL patients included in a prospective multicenter observational study (O-CLL1-GISL protocol, clinicaltrial.gov ID:NCT00917549) were used to assess the value and reproducibility of this score. To date, 468 Binet A patients were classified as low- (0 positive marker), intermediate- (1 positive marker), or high-risk (2 or 3 positive markers) using the progression risk score. The 3-year PFS probability was 91.7%, 82.9%, and 57.4% for low-, intermediate-, and high-risk (P < 0.0001) cases, respectively. These values were similar to those found in the original cohort. At Cox multivariate analysis, Rai stage, absolute lymphocyte count, progression risk score, and β-2 microglobulin maintained an independent prognostic impact on PFS. This score remained a predictor of progression when analysis was limited to 371 Rai 0 cases (P < 0.0001). Finally, the cells from the different CLL risk groups showed differences in their gene expression patterns. These results confirm the ability of this progression risk score to predict PFS among Binet A patients. The utility of the score was also extended by demonstrating that it retains prognostic value when applied exclusively to Rai 0 patients. Specific transcriptional patterns were significantly associated with risk groups

Prospective validation of a risk score based on biological markers for predicting progression free survival in Binet stage A chronic lymphocytic leukemia patients: results of hte multicenter O-CLL 1-GISL study / Gentile, M.; Cutrona, G.; Mosca, L.; Matis, S.; Fabris, S.; Lionetti, M.; Ilariucci, F.; Zupo, S.; Musolino, C.; Levato, L.; Molica, S.; Di Raimondo, F.; Vincelli, I.; Di Renzo, N.; Pesce, Emanuela Anna; Angrilli, F.; Federico, Massimo; Neri, A.; Ferrarini, M.; Morabito, F.. - In: AMERICAN JOURNAL OF HEMATOLOGY. - ISSN 0361-8609. - STAMPA. - 89 (7)(2014), pp. 743-750. [10.1002/ajh.23729]

Prospective validation of a risk score based on biological markers for predicting progression free survival in Binet stage A chronic lymphocytic leukemia patients: results of hte multicenter O-CLL 1-GISL study

PESCE, Emanuela Anna;FEDERICO, Massimo;
2014

Abstract

A risk score based on three biological features (CD38, ZAP-70, and IGHV mutational status) was previously developed to predict progression-free survival (PFS) in untreated Binet A CLL patients. Here we perform a score validation analysis in a prospective and independent cohort of patients. Biological markers (CD38, ZAP-70, and IGHV mutational status) and gene expression profiles (GEP) of leukemic cells from CLL patients included in a prospective multicenter observational study (O-CLL1-GISL protocol, clinicaltrial.gov ID:NCT00917549) were used to assess the value and reproducibility of this score. To date, 468 Binet A patients were classified as low- (0 positive marker), intermediate- (1 positive marker), or high-risk (2 or 3 positive markers) using the progression risk score. The 3-year PFS probability was 91.7%, 82.9%, and 57.4% for low-, intermediate-, and high-risk (P < 0.0001) cases, respectively. These values were similar to those found in the original cohort. At Cox multivariate analysis, Rai stage, absolute lymphocyte count, progression risk score, and β-2 microglobulin maintained an independent prognostic impact on PFS. This score remained a predictor of progression when analysis was limited to 371 Rai 0 cases (P < 0.0001). Finally, the cells from the different CLL risk groups showed differences in their gene expression patterns. These results confirm the ability of this progression risk score to predict PFS among Binet A patients. The utility of the score was also extended by demonstrating that it retains prognostic value when applied exclusively to Rai 0 patients. Specific transcriptional patterns were significantly associated with risk groups
89 (7)
743
750
Prospective validation of a risk score based on biological markers for predicting progression free survival in Binet stage A chronic lymphocytic leukemia patients: results of hte multicenter O-CLL 1-GISL study / Gentile, M.; Cutrona, G.; Mosca, L.; Matis, S.; Fabris, S.; Lionetti, M.; Ilariucci, F.; Zupo, S.; Musolino, C.; Levato, L.; Molica, S.; Di Raimondo, F.; Vincelli, I.; Di Renzo, N.; Pesce, Emanuela Anna; Angrilli, F.; Federico, Massimo; Neri, A.; Ferrarini, M.; Morabito, F.. - In: AMERICAN JOURNAL OF HEMATOLOGY. - ISSN 0361-8609. - STAMPA. - 89 (7)(2014), pp. 743-750. [10.1002/ajh.23729]
Gentile, M.; Cutrona, G.; Mosca, L.; Matis, S.; Fabris, S.; Lionetti, M.; Ilariucci, F.; Zupo, S.; Musolino, C.; Levato, L.; Molica, S.; Di Raimondo, F.; Vincelli, I.; Di Renzo, N.; Pesce, Emanuela Anna; Angrilli, F.; Federico, Massimo; Neri, A.; Ferrarini, M.; Morabito, F.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1026922
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