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

Bulian, Pietro, Shanafelt, Tait D., Fegan, Chris ORCID: https://orcid.org/0000-0001-9685-0621, 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 A worldwide multicenter analysis was performed using published and unpublished CLL series to evaluate the impact of CD49d as an overall (OS) and treatment-free survival (TFS) predictor.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: 31 Oct 2022 09:01
URI: https://orca.cardiff.ac.uk/id/eprint/79569

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