Characterization of chromosome 5 aberrations in TP53 mutated myeloid neoplasms with ≥5% blasts: An International TP53 Investigators Network (iTiN) study.

Abstract

Isolated chromosome 5/5q losses (-5/5q) without TP53 mutations are associated with favorable outcomes in myeloid neoplasms (MN) with <5% blasts. However, the clinical implication of concurrent -5/5q and TP53 aberrations in MN with ≥5% blasts is poorly understood. Patients with TP53-mutated MN carrying ≥5% blasts assessing the prognostic impact of -5/5q on 24-month overall survival (OS24) were examined. Of 587 patients, 515 (88%) exhibited -5/5q overwhelmingly in the context of a complex karyotype (98.3% vs. 61.1% complex karyotype without -5/5q; p < .0001) and multihit TP53 allelic state (88.3% vs. 56.9%; p < .0001). Proportions of patients with blasts ≥20% were comparable between groups with and without -5/5q; p = 0.26. Notably, patients with -5/5q exhibited significantly fewer coalterations; p < .0001. Looking at outcomes, presence of -5/5q was associated with shorter median 24-month overall survival (7.8 months vs. 11.2 months; p_Log-rank = .012), an effect restricted to subgroups with blasts <20% (p = .039; N = 163), absent -7/7q (p = .007; N = 225), or WHO5-defined single hit allelic state (p = 0.030; N = 91). Importantly, -5/5q retained independent adverse prognostic significance regardless of TP53 allelic state in a multivariable model. Furthermore, among the subset of 75 (13%) patients undergoing allogeneic stem cell transplantation, -5/5q predicted significantly shorter median 5-year posttransplant survival (16.2 months vs. median not reached; p_Log-rank = .009). These findings emphasize the independent prognostic relevance of chromosome 5/5q losses underscoring the clinical relevance of cytogenetic testing for -5/5q even in this high-risk cohort.