Individualizing IPSS Risk Assessment in Myelodysplastic Syndromes, by Additionally Taking into Account Age, Gender and French-American-British (FAB) Classification - A Multicenter Analysis.
Authors: Noesslinger Thomas , Tuechler Heinz , Germing Ulrich , Valent Peter , Krieger Otto , Haase Detlev , Stauder Reinhard , Pfeilstocker Michael 
Published: October 2019

Abstract
In Myelodysplastic Syndromes (MDS) the International Prognostic Scoring System (IPSS) is the golden standard to assess the patients risk profile. Although only three parameters were included in the score, namely the medullary blast cell count, the karyotype and the amount of cytopenias, multiple risk factors, among others age and gender, were discussed in its original publication (Greenberg et al., Blood89,6,1997:p2079–88). Their additional predictive importance was stated there, but not formally quantified. In a retrospective multicenter analysis (for sample details see below) the modulating impact of age, gender and FAB classification on the IPSS was studied and individualized score values of the IPSS for each age*gender*FAB group were estimated (see table below). While without consideration of age, gender and FAB classification the risk of a patient at the four IPSS levels is best represented by the values 0 to 3, these values vary considerably between age*gender*FAB subgroups, as e.g. an IPSS ‘low’ scoring female patient <66 years with RA/RARS would be assigned a score of −2.3, an otherwise equal male patient −0.4, indicating that especially the female patient faces a much lower risk than the average IPSS ‘low’ patient. The estimation of these scores is based on a Cox-PH model predicting survival and including significant main effects for the IPSS, age (<=66 years vs >66 years), gender and FAB classification (RA/RARS vs RAEB/RAEBT/CMML), as well as interactions between IPSS and gender, and age and FAB, expressed by the formula RR = ipss*.44 + sex*−.27+age66*.47+fab_gr*.41+(ipss:sex)*.36+(age66:fab_gr)−.60.
The IPSS/gender interaction shows that the IPSS differentiates much better in women than in men, the age/FAB interaction underlines that the FAB classification has more relevance in younger as compared to older patients. Sample details: In a series of 897 primary MDS patients treated with supportive care only, median survival was 47 months and the median follow up 56 months. The median age was 68 years. According to the FAB classification the distribution and the median survival duration were as follows: RA 341 pts, 70 mo; RARS 152 pts, 77 mo; RAEB 172 pts 20 mo; CMML 148 pts, 25 mo; RAEBT 84 pts, 11 mo. According to the IPSS the distribution and the median survival duration were as follows: low 268 pts (29,9%), 86 mo; int-1 285 pts (31,8%), 55 mo; int-2 158 pts (17,6%), 23 mo; high 186 pts (20,7%), 13 mo. These results are concordant with other published data, especially the original publication of the IPSS.
Conclusion: The reported table and formula are useful and convenient to substantially enhance the precision of the IPSS in predicting the risk of MDS patients.
IPSS Low Int-1 Int-2 High n.a. not applicaple all patients 0.0 1.0 2.0 3.0 male,<66,RA/RARS −0.4 0.2 0.8 n.a. female,<66,RA/RARS −2.3 −0.9 0.6 n.a. male,>66,RA/RARS 1.3 1.9 2.5 n.a. female,>66,RA/RARS −0.5 0.9 2.3 n.a. male,<66,RAEB/RAEBT/CMML n.a. 1.8 2.4 3.0 female,<66,RAEB/RAEBT/CMML n.a. 0.8 2.2 3.6 male,>66,RAEB/RAEBT/CMML n.a. 2.2 2.8 3.3 female,>66,RAEB/RAEBT/CMML n.a. 1.1 2.5 4.0