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

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    Author
    Leeksma, AC; Baliakas, P; Moysiadis, T; Puiggros, A; Plevova, K; Van der Kevie-Kersemaekers, A-M; Posthuma, H; Rodriguez-Vicente, AE; Tran, AN; Barbany, G; ...
    Date
    2020-01-23
    Source Title
    Haematologica: the hematology journal
    Publisher
    Ferrata Storti Foundation (Haematologica)
    University of Melbourne Author/s
    Tam, Constantine; Wall, Meaghan
    Affiliation
    Medicine and Radiology
    Metadata
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    Document Type
    Journal Article
    Citations
    Leeksma, A. C., Baliakas, P., Moysiadis, T., Puiggros, A., Plevova, K., Van der Kevie-Kersemaekers, A. -M., Posthuma, H., Rodriguez-Vicente, A. E., Tran, A. N., Barbany, G., Mansouri, L., Gunnarsson, R., Parker, H., Van den Berg, E., Bellido, M., Davis, Z., Wall, M., Scarpelli, I., Österborg, A. ,... Kater, A. P. (2020). Genomic arrays identify high-risk chronic lymphocytic leukemia with genomic complexity: a multi-center study.. Haematologica, 106 (1), pp.87-97. https://doi.org/10.3324/haematol.2019.239947.
    Access Status
    Access this item via the Open Access location
    URI
    http://hdl.handle.net/11343/254220
    DOI
    10.3324/haematol.2019.239947
    Open Access URL
    http://doi.org/10.3324/HAEMATOL.2019.239947
    Open Access at PMC
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7776256
    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.

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