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We conducted an integrative analysis on genetic abnormalities identified through cytogenetics and targeted next\u2010generation sequencing in 536 CLL patients receiving first\u2010line chemo(immuno)therapies (CIT) as part of two prospective trials. We evaluated the prognostic implications of the main abnormalities, with specific attention to their relative impact according to IGHV status. In the entire cohort, unmutated (UM)\u2010IGHV, complex karyotype, del(11q) and <jats:italic>ATM<\/jats:italic> mutations correlated significantly with shorter progression\u2010free survival (PFS). Focusing on the subset of mutated IGHV (M\u2010IGHV) patients, univariate analysis showed that complex karyotype, del(11q), <jats:italic>SF3B1<\/jats:italic> and <jats:italic>SAMHD1<\/jats:italic> mutations were associated with significant lower PFS. The prognostic influence varied based on the patient's IGHV status, as these abnormalities did not affect outcomes in the UM\u2010IGHV subgroup. <jats:italic>TP53<\/jats:italic> mutations had no significant impact on outcomes in the M\u2010IGHV subgroup. Our findings highlight the diverse prognostic influence of genetic aberrations depending on the IGHV status in symptomatic CLL patients receiving first\u2010line CIT. The prognosis of gene mutations and cytogenetic abnormalities needs to be investigated with a compartmentalized methodology, taking into account the IGVH status of patients receiving first\u2010line BTK and\/or BCL2 inhibitors.<\/jats:p>","DOI":"10.1111\/bjh.19459","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T06:48:36Z","timestamp":1713941316000},"page":"495-502","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Prognostic impact of genetic abnormalities in 536 first\u2010line chronic lymphocytic leukaemia patients without 17p deletion treated with chemoimmunotherapy in two prospective trials: Focus on IGHV\u2010mutated subgroups (a <scp>FILO<\/scp> study)"],"prefix":"10.1111","volume":"205","author":[{"given":"Florence","family":"Nguyen\u2010Khac","sequence":"first","affiliation":[{"name":"Unit\u00e9 de Cytog\u00e9n\u00e9tique, H\u00f4pital 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