New and Comprehensive Cytogenetic Prognostication and Categorization in MDS.

Abstract

The International Prognostic Scorig System (IPSS) was established on the basis of a multicentric analysis of 816 pts. with MDS with 327 individuals (40%) showing clonal cytogenetic abnormalities. Analyses of survival and clinical courses were performed for 11 cytogenetic subgroups. Although the IPSS represents a main and meritorious progress in prognostication in MDS it has shortcomings resulting from the limitated number of pts. Thus, little is known about the prognostic impact of rare and combined anomalies and a lot of abnormalities are assigned to the intermediate prognostic group without knowing their actual prognosis. It was our aim to refine the cytogenetic prognostic categorization in MDS. For this purpose we created a multicentric German-Austrian database of 2072 pts. with MDS and successful cytogenetics of whom 1080 individuals (52%) had clonal abnormalities. Of this group 1202 individuals were treated with supportive care only, and had a well-documented follow-up and blast count. For this group we defined 23 cytogenetic prognostic subgroups (at least 5 pts. with the same abnormality) also considering the number of accompanying abnormalities. Every subgroup was categorized in relation to the IPSS-categorization according to blast counts and a comparison of survival times. The following subgroups (all either isolated or with only one additional abnormality except the complex cases) were thus established: 9q- (median survival: not reached (nr), categorization: good); 15q- (nr, good); t(15q) (nr, good); 12p- (108, good); +21 (108, good); 5q- (77.2, good); −X (56.4, good); normal (53.4, good); −Y (39.0, good); t(1q) (34.7, good); t(7q) (34.7, good); t(11q) (32.1, good); −21 (32.0, good); 11q- (26.1, intermediate I); +8 (int I); +19 (19.8, int II); 7q- (19.0, int II); any 3 abnorm. (17.1, int II); complex with 3 abnormalties (17.0, int II); −7 (14.0, int II); complex with more than 3 abnormalities (8.7, poor); t(5q) (4.4, poor). Applying our new categorization the following results were obtained: good risk (n=802 pts., ms: 55.4 mo); int I (n=170, 29.4 mo); int II (n=103, 14.6 mo); poor (n=127, 8.1 mo). The differences between the respective Kaplan-Meier curves were highly significant (p=0.0000). Our findings could be the basis for a new comprehensive cytogenetic scoring system covering most pts. with MDS by a now well-known prognosis.