Abstract PURPOSE: Although CD49d is an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL), definitive validation evidence is lacking. A worldwide multicenter analysis was performed using published and unpublished CLL series to evaluate the impact of CD49d as an overall (OS) and treatment-free survival (TFS) predictor. PATIENTS AND METHODS: A training/validation strategy was chosen to find the optimal CD49d cutoff. The hazard ratio (HR) for death and treatment imposed by CD49d was estimated by pooled analysis of 2,972 CLLs; Cox analysis stratified by center and stage was used to adjust for confounding variables. The importance of CD49d over other flow cytometry-based prognosticators (eg, CD38, ZAP-70) was ranked by recursive partitioning. RESULTS: Patients with ≥ 30% of neoplastic cells expressing CD49d were considered CD49d+. Decrease in OS at 5 and 10 years among CD49d+ patients was 7% and 23% (decrease in TFS, 26% and 25%, respectively). Pooled HR of CD49d for OS was 2.5 (2.3 for TFS) in univariate analysis. This HR remained significant and of similar magnitude (HR, 2.0) in a Cox model adjusted for clinical and biologic prognosticators. Hierarchic trees including all patients or restricted to those with early-stage disease or those age ≤ 65 years always selected CD49d as the most important flow cytometry-based biomarker, with negligible additional prognostic information added by CD38 or ZAP-70. Consistently, by bivariate analysis, CD49d reliably identified patient subsets with poorer outcome independent of CD38 and ZAP-70. CONCLUSION: In this analysis of approximately 3,000 patients, CD49d emerged as the strongest flow cytometry-based predictor of OS and TFS in CLL. Comment in Prognostic and predictive factors in patients with chronic lymphocytic leukemia: relevant in the era of novel treatment approaches? [J Clin Oncol. 2014]

Bulian, P., Shanafelt, T., Fegan, C., Zucchetto, A., Cro, L., Nückel, H., et al. (2014). CD49d is the strongest flow cytometry-based predictor of overall survival in chronic lymphocytic leukemia. JOURNAL OF CLINICAL ONCOLOGY [10.1200/JCO.2013.50.8515].

CD49d is the strongest flow cytometry-based predictor of overall survival in chronic lymphocytic leukemia.

DEL POETA, GIOVANNI;
2014-03-20

Abstract

Abstract PURPOSE: Although CD49d is an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL), definitive validation evidence is lacking. A worldwide multicenter analysis was performed using published and unpublished CLL series to evaluate the impact of CD49d as an overall (OS) and treatment-free survival (TFS) predictor. PATIENTS AND METHODS: A training/validation strategy was chosen to find the optimal CD49d cutoff. The hazard ratio (HR) for death and treatment imposed by CD49d was estimated by pooled analysis of 2,972 CLLs; Cox analysis stratified by center and stage was used to adjust for confounding variables. The importance of CD49d over other flow cytometry-based prognosticators (eg, CD38, ZAP-70) was ranked by recursive partitioning. RESULTS: Patients with ≥ 30% of neoplastic cells expressing CD49d were considered CD49d+. Decrease in OS at 5 and 10 years among CD49d+ patients was 7% and 23% (decrease in TFS, 26% and 25%, respectively). Pooled HR of CD49d for OS was 2.5 (2.3 for TFS) in univariate analysis. This HR remained significant and of similar magnitude (HR, 2.0) in a Cox model adjusted for clinical and biologic prognosticators. Hierarchic trees including all patients or restricted to those with early-stage disease or those age ≤ 65 years always selected CD49d as the most important flow cytometry-based biomarker, with negligible additional prognostic information added by CD38 or ZAP-70. Consistently, by bivariate analysis, CD49d reliably identified patient subsets with poorer outcome independent of CD38 and ZAP-70. CONCLUSION: In this analysis of approximately 3,000 patients, CD49d emerged as the strongest flow cytometry-based predictor of OS and TFS in CLL. Comment in Prognostic and predictive factors in patients with chronic lymphocytic leukemia: relevant in the era of novel treatment approaches? [J Clin Oncol. 2014]
20-mar-2014
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/15 - MALATTIE DEL SANGUE
English
Con Impact Factor ISI
Bulian, P., Shanafelt, T., Fegan, C., Zucchetto, A., Cro, L., Nückel, H., et al. (2014). CD49d is the strongest flow cytometry-based predictor of overall survival in chronic lymphocytic leukemia. JOURNAL OF CLINICAL ONCOLOGY [10.1200/JCO.2013.50.8515].
Bulian, P; Shanafelt, T; Fegan, C; Zucchetto, A; Cro, L; Nückel, H; Baldini, L; Kurtova, A; Ferrajoli, A; Burger, J; Gaidano, G; DEL POETA, G; Pepper, C; Rossi, D; Gattei, V
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/99876
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