Time-dependent changes in mortality and transformation risk in MDS

In myelodysplastic syndromes (MDS) evolution of risk for disease progression or death has not been systematically investigated despite being crucial for correct interpretation of prognostic risk scores. In a multicenter retrospective study we describe changes in risk over time, the consequences for basal prognostic scores and their potential clinical implications. Major MDS prognostic risk scoring systems (IPSS, IPSS-R, WPSS, LRPSS) and their constituent individual predictors were analyzed in 7,212 primary untreated MDS patients from the IWG-PM database. Changes in risk of mortality and of leukemic transformation over time from diagnosis were described. In higher risk MDS, hazards regarding mortality and AML transformation diminished over time from diagnosis, whereas they remained stable in lower risk patients. After approximately 3.5 years, hazards in the separate risk groups became similar and essentially equivalent after five years. This fact led to loss of prognostic power of different scoring systems considered more pronounced for survival. Inclusion of age resulted in increased initial prognostic power for survival and less attenuation in hazards. If needed for practicability in clinical management the differing development of risks suggested a reasonable division into lower and higher risk MDS based on the IPSS-R at a cut-off of 3.5 points. Our data regarding time-dependent performance of prognostic scores reflect the disparate change of risks in MDS subpopulations. Lower risk patients at diagnosis remain “constant lower risk", while "initially high risk" patients demonstrate decreasing risk over time. This change of risk should be considered in clinical decision making.