Modification of WPSS for the Time of Diagnosis Retains Its Prognostic Impact and Confirms Transfusion Dependency as An Important Parameter Affecting Survival in Early MDS Patients with Isolated Erythroid Dysplasia.
Authors: Cermak Jaroslav , Mikulenkova Dana , Kacirkova Petra , Michalova Kyra 
Published: April 2020

Abstract
We attempted to overcome a limitation of WPSS at the time of diagnosis by replacement of transfusion dependency with initial Hb level. Hb &lt; 80 g/l was scored 1, Hb ≥ 80 g/l was scored 0. This adjustment was tested in a retrospective analysis of 107 non-transplanted patients with early MDS without of excess of blasts diagnosed between 1980 and 2004. Kaplan Meier estimates for 5 years survival were 58%, 57%, 36% and 12% for patients with very low, low, intermediate and high risk scored at the time of diagnosis according to modified WPSS. A significant difference in overall survival was present between patients with score &lt; 2 and ≥ 2 and in leukemia free survival between patients with score &lt; 1 and ≥1 (P=0.02). An analysis of individual WPSS parameters revealed a significant difference in median survival between patients receiving ≤ 2 units and those receiving &gt; 2 units of RBC transfusions/month (46.1 vs. 26.9 months, respectively, P=0.03), between patients with RA+RARS+5q-syndrome and those with RCMD+RCMD-RS (45.4 vs. 27.8 months, respectively, P=0.02) and between patients with good karyotype and intermediate or poor karyotype according to IPSS (48.0 vs. 22.0 months, respectively, P=0.02). An impact of transfusion dependency on survival was validated by univariate and multivariate regression analysis of different clinical and laboratory variables. Leukemic progression was the most important parameter affecting survival in both univariate (χ2=47.7, P=0,001) and multivariate (P&lt;0.0001) analysis and was the only independent variable affecting survival in patients with progressive disease. In patients without MDS progression, administration of &gt; 2 units of RBC transfusions/month was the only independent variable with adverse impact on survival in patients with unilineage erythroid dysplasia (P=0.02). In patients with multilineage dysplasia only heavy transfusion dependence (&gt; 3 TU RBC/month) in combination with serum ferritin &gt; 2000 μg/l adversely affected survival (P=0.03). In conclusion, modification of WPSS by replacement of transfusion dependency with initial Hb level &lt; 80 g/l retained its prognostic relevance and allowed to identify even at the time of diagnosis a potentially risk subset of early MDS patients with intermediate and high score and limited survival (&lt; 40% at 5 years). Our results also confirmed a significant negative impact of transfusion dependency on survival in at least a subset of patients with early MDS. This subgroup is characterized by unilineage dysplasia limited to erythropoiesis in combination with dependency on &gt; 2 TU of RBC per month. These patients have usually a prolonged survival enabling development of heavy transfusion iron overload and thus represent the main target group for intensive chelation therapy. The study was supported by scientific grant NR 9235-3 from the Czech Ministry of Health.