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. TP53 mutation prevalence was significantly elevated in patients with clone size of ≥25% compared with those with <25% (34.2% vs 3%; P = .07). Complex karyotypes with clone size of ≥75% demonstrated superior response to hypomethylating agents (20.8% vs 10%; P = .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.