Endothelial Activation and Stress Index (EASIX) Is Associated with Fluid Overload and Survival in Recipients of Allogeneic Stem Cell Transplantation

Background Fluid overload (FO) grade ≥ 2 (more that 10% weight gain from baseline) has recently been recognized as an important toxicity associated with non-relapse mortality in recipients of allogeneic stem cell transplantation (alloSCT). 1 The causes for fluid accumulation remain unclear. We hypothesized that endothelial damage due to treatments received prior to alloSCT may be associated with this toxicity and sought to determine whether the Endothelial Activation and Stress Index 2 (EASIX), (defined as lactate dehydrogenase (U/L)  ×  creatinine (mg/dL)/ thrombocytes (10 9  cells per L), correlates with grade ≥ 2 FO and overall survival (OS) in 2 cohorts of recipients of alloSCT at our institution. The first cohort included 145 recipients of haploidentical (haplo) transplantation, and the second 449 recipients of alloSCT from HLA-matched donors, as previously described. 1 Methods Predictors (listed in table) of grade ≥ 2 FO and 6-months OS were evaluated using Cox's proportional hazards regression analysis on univariate analysis, and classification and regression tree (CART) analysis on multivariate (MV) analysis. EASIX scores were evaluated based on log2 transformed values. Results Median log2 EASIX score in the 2 cohorts was 2.4 (IQR: 1.3, 3.7) and 2.5 (IQR 1.4, 3.9) at admission, and 3.1 (IQR 2.2, 3.9) and 2.8 (IQR 1.7, 3.9) at transplant, respectively. CART analysis identified EASIX > 4.4 at admission to be an independent predictor of grade ≥ 2 FO in the haplo (HR=7.5, p 55 years recipients in the haplo cohort, and diabetes (HR=35, p=0.001) and age >60 years (HR=8.1, p=0.06) in the matched cohort. In patients with grade ≥ 2 FO, EASIX >4.4 at SCT was the only significant predictor of OS (HR=4.1, p=0.002). This effect was consistent in both cohorts (Figure A). In patients with grade 0-1 FO, MV analysis showed EASIX >3, comorbidity index score >3, and active disease at SCT to be independent adverse predictors of OS. OS was lowest (60%, reference) in patients with EASIX> 3 and comorbidity score >3, and this effect was consistent in both cohorts (Figure B). OS was significantly higher in patients with EASIX >3 and comorbidity score ≤3 (73%, p