Abstract: Endothelial Activation and Stress Index (EASIX) predicts non-relapse mortality (NRM) when assessed prior to hematopoietic cell transplantation (HCT). We sought to determine if changes in EASIX post-HCT may be an informative marker of NRM. We evaluated 509 adults who underwent reduced intensity, unmodified (N=149, 29%) or myeloablative, ex-vivo CD34+-selected allo-HCT (N=306, 71%) between 2008-2016. Unmodified allo-HCT patients received tacrolimus-based GVHD prophylaxis while CD34+-selected patients received no planned immunosuppression. EASIX (LDH x creatinine/platelet count) was calculated continuously until 1-year post-HCT. Log transformation using base 2 (log2) was applied to all EASIX variables to reduce skew. Three hundred and sixty patients (71%) received CD34+-selected and 149 (29%) unmodified allo-HCT. Among all patients, EASIX scores increased rapidly, peaked at day +8, then declined rapidly until day +33. Thereafter, scores declined gradually but remained above pre-HCT baseline. In unmodified HCT, scores appeared higher over time than in CD34+-selected patients. EASIX discrimination of NRM was highest around day +180 (concordance index=0.85) in both platforms, but the prognostic impact of EASIX across timepoints differed between the two platforms. Mean EASIX scores were higher in men (mean log2 +0.52) and in patients who developed grade 2-4 GVHD (+0.81) and lower in patients who received matched versus mismatched donors (-0.81, all P<0.01). EASIX scores are dynamic and variably concordant with NRM when analyzed longitudinally, and patterns differ between HCT platforms. Compared to pre-HCT evaluation, post-HCT EASIX scores may better predict risk of NRM as patients acquire additional endothelial injury and toxicities.

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