New Prognostic Data on Rare Cytogenetic Abnormalities in MDS: A Collaborative Study of the International Working Group on MDS Cytogenetics

Introduction: Several recent publications have advanced our knowledge of the prognostic significance of clonal cytogenetic abnormalities in MDS, yet the genetic risk assessment of the rare karyotypic aberrations in MDS patients (pts) remains unknown. Using the German-Austrian (G-A) Cytogenetics Database, we previously defined 24 cytogenetic prognostic subgroups; however, 12 subgroups characterized by non-complex (isolated or one additional abnormality only) karyotypes with del(9q), del(15q), t(15q), del(12p), −X, t(1q), t(7q), t(17q), −21, t(11q23), +19, t(5q) were observed infrequently (<10 pts) and considered too few for an informative risk assessment. To increase the number of informative pts and expand/validate the statistical robustness of these rare cytogenetic subgroups, an international collaboration was initiated and promoted under the auspices of the MDS Foundation.

Patients and Methods: A total of 90 new MDS pts with rare recurring abnormalities was collected from 12 MDS Foundation Centers of Excellence, of which 66 pts fulfilled the non-complex requirement. Survival was estimated by Kaplan-Meier analysis and restricted to pts treated by supportive care only. The final analysis included 108 pts: del(9q)(n=10); del(12p)=17; −X=10; t(1q)=13; t(7q)=14; −21=12; t(11q23)=12; +19=10; t(5q)=10. The frequency of non-complex del(15q), t(15q) and t(17q) remained below ten pts and deemed ineligible for further analysis at this time.

Results: The pooled international data showed an excellent correlation with the G-A data set in 6 of 10 cytogenetic subgroups: t(7q): 34.7 months (mo.) median survival (G-A) vs. 34.7 mo. (new data), del(9q): not reached vs. 63.1 mo., t(11q23): 20.0 vs. 28.0 mo, del(12p): 108.0 mo. vs. not reached, +19: 19.8 vs. 21.7 mo., −21: 32.0 vs. 35.0 mo. A moderate correlation was found for t(1q): 34.7 mo. vs. not reached and for del(15q): not reached vs. 26.7 mo. Discordant median survival was observed for t(5q): 4.4 mo. vs. not reached and −X: 56.4 mo. vs. 15.7 mo.

Conclusions: Through an international collaboration, we were able to define the prognostic impact of nine distinct yet infrequent, recurring cytogenetic aberrations observed in MDS pts. The discordant median survival differences observed in two subgroups may be attributed to various translocation partners and/or secondary abnormalities. Even though data collection remains ongoing, the current results expand and refine the cytogenetic prognostic classification system for pts suffering from MDS and underscore the need for standardized cytogenetic testing in MDS for further international collaborations.