{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:21:21Z","timestamp":1792120881266,"version":"4.4.0"},"reference-count":43,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2014,3,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>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 A worldwide multicenter analysis was performed using published and unpublished CLL series to evaluate the impact of CD49d as an overall (OS) and treatment-free survival (TFS) predictor.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>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\u2013based prognosticators (eg, CD38, ZAP-70) was ranked by recursive partitioning.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Patients with \u2265 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 \u2264 65 years always selected CD49d as the most important flow cytometry\u2013based 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In this analysis of approximately 3,000 patients, CD49d emerged as the strongest flow cytometry\u2013based predictor of OS and TFS in CLL.<\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2013.50.8515","type":"journal-article","created":{"date-parts":[[2014,2,11]],"date-time":"2014-02-11T06:08:13Z","timestamp":1392098893000},"page":"897-904","source":"Crossref","is-referenced-by-count":168,"title":["CD49d Is the Strongest Flow Cytometry\u2013Based Predictor of Overall Survival in Chronic Lymphocytic Leukemia"],"prefix":"10.1200","volume":"32","author":[{"given":"Pietro","family":"Bulian","sequence":"first","affiliation":[{"name":"Pietro Bulian, Antonella Zucchetto, and Valter Gattei, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Centro di Riferimento Oncologico, Aviano; Lilla Cro and Luca Baldini, Fondazione IRCCS C\u00e0 Granda, Ospedale Maggiore Policlinico and Universit\u00e0 degli Studi, Milan; Gianluca Gaidano and Davide Rossi, Amedeo Avogadro University of Eastern Piedmont, Novara; Giovanni Del Poeta, Tor Vergata University, S. 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