Association of Baseline Neoplastic Microenvironment, Early Progression and Overall Survival in High-Risk Myelodysplastic Syndromes Treated with Azacytidine

Abstract Neoplastic environment plays important role in growth of malignant cells and their resistance to therapy. In this trial, we investigated a group of 46 patients with newly diagnosed high-risk myelodysplastic syndrome (MDS), who were indicated to treatment with azacytidine. We evaluated baseline serum levels of cytokines, soluble adhesion molecules and soluble cytokine receptors. We found Interleukin (IL)-1α correlated with IL-2, EGF correlated with VEGF and P-SEL, TNFR-1 correlated with TNFR-2. Platelet count correlated with P-SEL. Correlation of leukocyte count with E-selectin and P-selectin were moderate, correlation with MMP-9 was close to statistical significance. Haemoglobin levels, age, cytogenetics, LDH and TP53 mutation status were not confirmed significantly altering the levels of evaluated factors. Higher levels of IFN-γ and L-SEL were associated with early on-treatment progression, which has been identified as the strongest independent risk factor for overall survival. Despite the size of the cohort and full awareness of limited statistical power of such studies, our findings confirm the recently published prognostic value of IL-4 in MDS. Furthermore, based on multivariate analysis, we identified IL-10 as a possible independent marker of overall survival, and L-SEL together with TNFR-2 as candidate prognostic markers for overall survival independent of standard prognostic variables. IFN-γ was not confirmed as having predictive value in this cohort. These data show a high complexity of mechanisms affecting neoplastic environment and identify factors possibly associated with patient prognosis irrespective of standard prognostic indicators.