Acquisition of cytogenetic abnormalities in patients with IPSS defined lower-risk myelodysplastic syndrome is associated with poor prognosis and transformation to acute myelogenous leukemia

We hypothesized that the dynamic acquisition of cytogenetic abnormalities (ACA) during the follow up of myelodysplastic syndromes (MDS) could be associated with poor prognosis. We conducted a retrospective analysis of 365 patients with IPSS low or intermediate-1 risk MDS who had at least two consecutive cytogenetic analyses during the follow up. Acquisition of cytogenetic abnormalities was detected in 107 patients (29%). The most frequent alteration involved chromosome 7 in 21% of ACA cases. Median transformation-free and overall survival for patients with and without ACA were 13 vs. 52 months (P=0.01) and 17 vs. 62 months (P=0.01), respectively. By fitting ACA as a time-dependent covariate, multivariate Cox regression analysis showed that patients with ACA had increased risk of transformation (HR=1.40; P=0.03) or death (HR=1.45; P=0.02). Notably, female patients with therapy-related MDS (t-MDS) had an increased risk of developing ACA (OR=5.26; P<0.0001), although subgroup analysis showed that prognostic impact of ACA was not evident in t-MDS. In conclusion, ACA occurs in close to one third of patients with IPSS defined lower risk MDS, more common among patients with t-MDS, but has a significant prognostic impact on de novo MDS. Am. J. Hematol. 88:831-837, 2013.