Correlation of Cytogenetic Findings with Morphology, Clinical Course and Prognosis in 2124 Patients with MDS.
Authors: Haase D. , Steidl C. , Schanz J. , Schabla R. , Pfeilstöcker M. , Nösslinger T. , Hildebrandt B. , Kuendgen A. , Lübbert M. , Kunzmann B. , Giagounidis A. , Aul C. , Trümper L. , Krieger O. , Fonatsch C. , Valent P. , Stauder R. , Germing U. 
Published: April 2020

Cytogenetic abnormalities are observed in 30%–80% of MDS pts and correlate with morphologic features, clinical course, prognosis, and response to therapy. Cytogenetic heterogeneity hampers investigation, and little is known about rarer abnormalities and combinations of abnormalities. Furthermore, it has not yet been possible to compare the effects of different therapies within cytogenetic entities. To address such issues, we have generated a large, unique database comprising morphologic, clinical, cytogenetic, and follow-up data from MDS pts at 8 institutions in Austria and Germany. So far, we have data on 2124 pts with a median age of 65.7 yr and a male: female ratio of 1.29. 1981 pts (93.3%) had primary and 143 had secondary MDS. FAB classification of pts: RA 589 (27.7%); RARS 256 (12.1%); RAEB 424 (20%); RAEB-T 311 (14.6%); CMML 287 (13.5%); MDS-AL 132 (4.2%). WHO classification (available in 595 pts): 5q- syndrome 71 (11.9%); RA 46 (7.7%); RARS 26 (4.4%); RCMD 164 (27.6%); RSCMD 77 (12.9%); RAEB-I 90 (15.1%); RAEB-II 121 (20.3%). Cytogenetic analyses were successful in 2072 pts (97.6%) with a mean of 21.9 completely analyzed metaphases. The mean number of aberrations per case was 1.52. 1080 pts (52.1%) had clonal abnormalities. Cytogenetic characteristics are shown in Figure 1. IPSS cytogenetic risk: good 1217 pts (58.7%); intermediate 401 (19.4%); unfavorable: 454 (21.9%). Follow-up data were available in 1841 pts for a mean of 29.2 mo. Supportive care was given to 1286 pts (60.6%), chemotherapy to 462 (21.8%), amifostine to 22 (0.1%), and therapeutic data were unavailable in 354. Median survival by IPSS cytogenetic risk, karyotype complexity, and influence of additional cytogenetic abnormalities in patients with isolated 5q deletion and trisomy 8 are shown in Table 1. Prognostic data of other isolated and combined abnormalities (-7,-20/20q-,-Y) as well as rarer abnormalities (3q, 9q-, +11, -12/12p-, -13/13q-, -17/17p-, +21 and others) will be presented, as will the influence of different therapies on survival in genetic entities. By FAB classification, there were no significant differences in the distribution of cytogenetic risk groups between RA and RARS and between RAEB and RAEB-T. By WHO classification, the 5q- syndrome exclusively displayed favorable karyotypes; no unfavorable abnormalities were observed in RARS (WHO) in contrast to RARS (FAB), and no significant differences were observed between RAEB-I and RAEB-II. In conclusion, additional abnormalities modulate the prognostic value of the primary cytogenetic changes in different ways that have to be delineated for each abnormality. Since novel therapies such as IMiDs/lenalidomide are effective in distinct cytogenetic entities, a better knowledge of cytogenetically defined subgroups is urgently needed.

Figure 1, Table 1 Figure 1, Table 1.