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CD49d Is the strongest flow cytometry–based predictor of overall survival in chronic lymphocytic leukemia

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posted on 2023-06-09, 12:41 authored by Pietro Bulian, Tait D Shanafelt, Chris Fegan, Antonella Zucchetto, Lilla Cro, Holger Nückel, Luca Baldini, Antonina V Kurtova, Alessandra Ferrajoli, Jan A. Burger, Gianluca Gaidano, Giovanni Del Poeta, Christopher PepperChristopher Pepper, Davide Rossi, Valter Gattei
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 A worldwide multicenter analysis was performed using published and unpublished CLL series to evaluate the impact of CD49d as an overall (OS) and treatment-free survival (TFS) predictor.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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Journal of Clinical Oncology

ISSN

0732-183X

Issue

9

Volume

32

Page range

897-904

Department affiliated with

  • Clinical and Experimental Medicine Publications

Research groups affiliated with

  • Haematology Research Group Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-03-28

First Open Access (FOA) Date

2018-03-28

First Compliant Deposit (FCD) Date

2018-03-28

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