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

• Cytogenetic clone size significantly correlates with cell counts, blast percentage, mutation status, and treatment response.

• Clone size is an independent prognostic factor for both OS and LFS, further refining the predictive capabilities of IPSS-R and IPSS-M.

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 MDS patients using G-banding and FISH. 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 ≥25% compared to those with <25% (34.2% vs. 3%; P = .07). Complex karyotypes with clone size ≥ 75% demonstrated superior response to hypomethylating agents (20.8% vs. 10%; P = .03). Crucially, clone size ≥ 25% independently predicted overall survival (OS) and leukemia-free survival (LFS), regardless of IPSS-R or IPSS-M. 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.