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

Bulian, Pietro, Shanafelt, Tait D., Fegan, Chris, Zucchetto, Antonella, Cro, Lilla, Nuckel, Holger, Baldini, Luca, Kurtova, Antonia V., Ferrajoli, Alessandra, Burger, Jan A., Gaidano, Gianluca, Del Poeta, Giovanni, Pepper, Chris, Rossi, Davide and Gattei, Valter 2014. CD49d is the strongest flow cytometry-based predictor of overall survival in chronic lymphocytic leukemia. Journal of Clinical Oncology 32 (9) , pp. 897-904. 10.1200/JCO.2013.50.8515

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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 A worldwide multicenter analysis was performed using published and unpublished CLL series to evaluate the impact of CD49d as an overall (OS) and treatment-free survival (TFS) predictor.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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher:	American Society of Clinical Oncology
ISSN:	0732-183X
Last Modified:	19 Jan 2021 09:45
URI:	https://orca.cardiff.ac.uk/id/eprint/79569

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