Detailed analysis of clonal evolution and cytogenetic evolution patterns in patients with myelodysplastic syndromes (MDS) and related myeloid disorders

Clonal cytogenetic evolution (CE) (i.e., acquisition of new chromosomal aberrations over time) is relevant for the progression of myelodysplastic syndromes (MDS). We performed detailed analysis of CE in 729 patients with MDS and related disorders. Patients with CE showed shorter survival (median OS 18.0 versus 53.9 months; P < 0.01), higher leukemic transformation rate (48.0% versus 21.4%; P < 0.01) and shorter intervals to leukemic transformation (P < 0.01). Two main CE patterns were detected: early versus late CE (median onset 5.3 versus 21.9 months; P < 0.01) with worse survival outcomes for early CE. In the case of CE, del (7q)/−7 (P = 0.020) and del (17p) (P = 0.002) were especially unfavorable. Extending the evolution patterns from Tricot et al. (1985) forming five subgroups, prognosis was best (median OS not reached) in patients with “transient clones/changing clone size”, whereas those with “CE at diagnosis” showed very poor outcomes (P < 0.01 for comparison of all). Detailed sequential cytogenetic analysis during follow-up improves prognostication in MDS patients and acknowledges the dynamic biology of the disease. Evidence, time-point, and patterns of cytogenetic clonal evolution should be included into future prognostic scoring systems for MDS.