Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: A multi-center study

Alexander C. Leeksma, Panagiotis Baliakas, Theodoros Moysiadis, Anna Puiggros, Karla Plevova, Anne Marie van der Kevie-Kersemaekers, Hidde Posthuma, Ana E. Rodriguez-Vicente, Anh Nhi Tran, Gisela Barbany, Larry Mansouri, Rebeqa Gunnarsson, Helen Parker, Eva van den Berg, Mar Bellido, Zadie Davis, Meaghan Wall, Ilaria Scarpelli, Anders Österborg, Lotta HanssonMarie Jarosova, Paolo Ghia, Pino Poddighe, Blanca Espinet, Sarka Pospisilova, Constantine Tam, Loïc Ysebaert, Florence Nguyen-Khac, David Oscier, Claudia Haferlach, Jacqueline Schoumans, Marian Stevens-Kroef, Eric Eldering, Kostas Stamatopoulos, Richard Rosenquist, Jonathan C. Strefford, Clemens Mellink, Arnon P. Kater*, ERIC, the European Research Initiative on CLL

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Complex karyotype (CK) identified by chromosome-banding analysis (CBA) has shown prognostic value in chronic lymphocytic leukemia (CLL). Genomic arrays offer high-resolution genome-wide detection of copy-number alterations (CNAs) and could therefore be well equipped to detect the presence of a CK. Current knowledge on genomic arrays in CLL is based on outcomes of single center studies, in which different cutoffs for CNA calling were used. To further determine the clinical utility of genomic arrays for CNA assessment in CLL diagnostics, we retrospectively analyzed 2293 arrays from 13 diagnostic laboratories according to established standards. CNAs were found outside regions captured by CLL FISH probes in 34% of patients, and several of them including gains of 8q, deletions of 9p and 18p (p<0.01) were linked to poor outcome after correction for multiple testing. Patients (n=972) could be divided in three distinct prognostic subgroups based on the number of CNAs. Only high genomic complexity (high-GC), defined as 5 CNAs emerged as an independent adverse prognosticator on multivariable analysis for time to first treatment (Hazard ratio: 2.15, 95% CI: 1.36-3.41; p=0.001) and overall survival (Hazard ratio: 2.54, 95% CI: 1.54-4.17; p<0.001; n=528). Lowering the size cutoff to 1 Mb in 647 patients did not significantly improve risk assessment. Genomic arrays detected more chromosomal abnormalities and performed at least as well in terms of risk stratification compared to simultaneous chromosome banding analysis as determined in 122 patients. Our findings highlight genomic array as an accurate tool for CLL risk stratification.

Original languageEnglish
JournalHaematologica
Volume105
Issue number5
DOIs
Publication statusPublished - Jan 2020

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