The Pretherapy Endothelial Activation and Stress Index (EASIX) in Patients with Newly Diagnosed Acute Myeloid Leukemia: A Pilot Study

Abstract

Background/Objectives: The endothelial activation and stress index (EASIX; serum creatinine times lactate dehydrogenase/peripheral blood platelet count) seems to reflect endothelial cell activation/dysfunction. Furthermore, endothelial cells support acute myeloid leukemia (AML) cell proliferation and survival, and high bone marrow microvascular density is associated with adverse prognosis in human AML. Methods: We investigated the pretreatment EASIX score in 160 AML patients (promyelocytic variants excluded) at the time of diagnosis before initiation of intensive cytarabine-based anti-AML therapy. Results: We detected a significant association between the pretreatment EASIX score and the monocytic AML cell phenotype (Fisher’s test, p = 0.0007). A weaker association was observed between a high pretreatment EASIX score and C-reactive protein levels (Spearman’s test, p = 0.017). We could not detect any significant difference in 5-year overall survival when comparing patient subsets with a pretreatment EASIX score below versus above the median cohort level (Kaplan–Meier’s test, p = 0.84), and the overall survival did not differ when comparing overall survival for the two contrasting upper and lower quartiles either (p = 0.88). Furthermore, the 5-year posttransplant survival did not differ between allotransplant recipients (n = 58) with a pretreatment (i.e., at the time of first diagnosis) EASIX score below versus above the cohort median level (p = 0.55). Finally, the 5-year overall survival did not differ when comparing patients with low versus high modified EASIX scores either (p = 0.46). Conclusions: Our study suggests that the pretherapy EASIX score does not have any prognostic impact in non-promyelocytic AML patients receiving conventional intensive AML therapy. This is different from patients with promyelocytic AML variants, in whom a high EASIX score is associated with increased mortality. However, EASIX scoring should be further investigated in AML patients who receive new targeted therapies, including BCL2-inhibition, which is less effective in monocytic AML variants.