Clinical correlation and prognostic impact of cytogenetic clone size for myelodysplastic syndromes/neoplasm

Most myelodysplastic syndromes/neoplasms (MDS) risk stratification models dichotomize conventional cytogenetic abnormalities into present or absent, neglecting the prognostic impact of clone size (percentage of the total cells/metaphases harboring the chromosome abnormality). We investigated the prognostic value of clone size in 1001 patients with MDS using G-banding and fluorescence in situ hybridization. Clone size correlated with anemia severity and thrombocytosis in del(5q) cases, and with anemia and blast percentage in complex karyotypes. <i>TP53</i> mutation prevalence was significantly elevated in patients with clone size of ≥25% compared with those with <25% (34.2% vs 3%; <i>P</i> = .07). Complex karyotypes with clone size of ≥75% demonstrated superior response to hypomethylating agents (20.8% vs 10%; <i>P</i> = .03). Crucially, clone size of ≥25% independently predicted overall survival and leukemia-free survival, regardless of revised International Prognostic Scoring System (IPSS) or molecular IPSS. Our findings establish clone size as a robust prognostic factor in MDS, warranting its integration into clinical practice and potential incorporation into risk stratification models.