{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T13:35:52Z","timestamp":1791207352317,"version":"4.1.0"},"reference-count":51,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,8,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Complex karyotypes have been associated with inferior outcomes in chronic lymphocytic leukemia (CLL) treated with chemoimmunotherapy (CIT), whereas their prognostic impact in the context of venetoclax-based treatments is still debated. In this prospective analysis on karyotype complexity in CLL, we evaluated the impact of complex (\u22653 chromosomal aberrations [CAs], CKTs) and highly complex karyotypes (\u22655 CAs; hCKTs) as well as specific aberrations in previously untreated patients without TP53 aberrations undergoing either CIT or time-limited venetoclax-based therapies in the phase 3 GAIA\/CLL13 trial. Karyotype analyses were available for 895 of 926 patients (96.7%), of whom 153 (17%) had a CKT and 43 (5%) hCKT. In the CIT arm, CKT was associated with shorter progression-free survival (PFS) (hazard ratio [HR] 2.58; 95% confidence interval [95% CI], 1.54-4.32; P\u00a0&amp;lt; .001) and overall survival (HR, 3.25; 95% CI, 1.03-10.26; P\u00a0= .044). In the pooled venetoclax arms, a multivariable analysis identified hCKTs (HR, 1.96; 95% CI, 1.03-3.72; P\u00a0= .041), but not CKTs, as independent adverse prognosticators for PFS. The presence of translocations (unbalanced and\/or balanced) was also independently associated with shorter PFSs in the venetoclax arms. CIT led to the acquisition of additional CAs (mean CAs, 2.0-3.4; from baseline to CLL progression), whereas karyotype complexity remained stable after venetoclax-based treatments (2.0, both time points). This analysis establishes highly complex karyotypes and translocations as adverse prognostic factors in the context of venetoclax-based combination treatments. The findings of this study support the incorporation of karyotyping into the standard diagnostic workup of CLL, because it identifies patients at high risk of poor treatment outcomes and thereby improves prognostication. This trial was registered at www.clinicaltrials.gov as #NCT02950051.<\/jats:p>","DOI":"10.1182\/blood.2023019634","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T15:04:04Z","timestamp":1683903844000},"page":"446-459","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":43,"title":["High karyotypic complexity is an independent prognostic factor in patients with CLL treated with venetoclax combinations"],"prefix":"10.1182","volume":"142","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6593-0140","authenticated-orcid":false,"given":"Moritz","family":"F\u00fcrstenau","sequence":"first","affiliation":[{"name":"1Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German CLL Study Group, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0413-9029","authenticated-orcid":false,"given":"Yvonne J.","family":"Thus","sequence":"additional","affiliation":[{"name":"2Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Robrecht","sequence":"additional","affiliation":[{"name":"1Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German CLL Study Group, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens H. M.","family":"Mellink","sequence":"additional","affiliation":[{"name":"3Genome Diagnostics Laboratory, Section Cytogenetics, Department of Human Genetics, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3515-6198","authenticated-orcid":false,"given":"Anne-Marie","family":"van der Kevie-Kersemaekers","sequence":"additional","affiliation":[{"name":"3Genome Diagnostics Laboratory, Section Cytogenetics, Department of Human Genetics, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Dubois","sequence":"additional","affiliation":[{"name":"2Department of Hematology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"von Tresckow","sequence":"additional","affiliation":[{"name":"4Clinic for Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Patz","sequence":"additional","affiliation":[{"name":"1Department I of Internal Medicine, Faculty of Medicine and University Hospital Cologne, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, German CLL Study Group, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gregor","sequence":"additional","affiliation":[{"name":"5Division of Hematology, Cantonal Hospital of Lucerne, Lucerne, Switzerland"},{"name":"6Swiss Group for Clinical Cancer Research, Berne, 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