Easix Score Predicts Overall Survival and Non-Relapse Mortality in Elderly Patients Undergoing Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic cell transplantation (allo-HSCT) has seen marked growth among older adults, where chronological age is no longer a barrier to transplant. As Elderly patients are at significantly higher risk of transplantation, estimation of the mortality risk in this population remains a key issue. The Endothelial Activation and Stress Index (EASIX) is a biomarker-based laboratory formula,which was originally designed to predict mortality in patients with acute graft-versus-host disease (GVHD).However, the utility of EASIX as a prognostic indicator in elderly transplant patients has not been investigated. Therefore, the aim of this study was to assess the capacity of EASIX in predicting transplantation risk and complications in an elderly cohort of patients undergoing haploidentical HSCT at various time points and to identify optimal pre-transplantation EASIX cut-off values that would enhance clinical practice. This retrospective study included elderly patients (≥60 years old) who underwent haploidentical HSCT at twelve transplant centres in Zhejiang Province, China, between April 2016 and November 2023. The EASIX scores (lactate dehydrogenase × creatinine/platelets) were calculated at 0 to 30 days before initiating the conditioning regimen (EASIX-pre), at day 0 post-HSCT (EASIX-d0),at day 7 post-HSCT (EASIX-d7), at day14 post-HSCT(EASIX-d14), at day 28 post-HSCT (EASIX-d28), at day 56 post-HSCT(EASIX-d56) and at day 100 post-HSCT (EASIX-d100). In order to reduce bias, the EASIX scores were converted to a log2 form of analysis (log2-EASIX). The median age of all patients (n=164) was 63.5 years (range: 60.0-71.9 years). Acute myeloid leukaemia (n=71, 43%) and myelodysplastic syndromes (n=54, 33%) were the most common baseline diagnoses. All patients underwent haploidentical HSCT, and 91% (n=150) of patients received reduced-intensity conditioning. At day+100, the cumulative incidences of I-IV aGVHD and transplantation-associated thrombotic microangiopathy (TA-TMA) were 28.7% and 3.7%, respectively. The incidence of cGVHD at two year was 30.6%. With a median follow-up period of 14 months, the 2-year OS, NRM, and relapse incidence were 54.7%,28.8%, and 18.8%, respectively. EASIX scores exhibited a rapid increase after HSCT and reaching a peak on day +7 , followed by a slight decline until day +28, but remained above the pre-HCT baseline. The log2-EASIX-PRE(continuous variable) was significantly associated with worse OS (univariate analysis;[HR],1.25;95% CI,1.07 to 1.47;p= 0.005) and higher NRM (univariate analysis; [HR],1.32; 95% CI, 1.08 to1.62; p = 0.007), but not associated with relapse (univariate analysis; [HR], 0.98; 95% CI, 0.78 to 1.23; p = 0.86). Similarly, log2-EASIX-d0 ([HR], 1.25; P =0.021),log2-EASIX-d7 ([HR],1.40;P =0.015),log2-EASIX-d14 ([HR], 1.40;P =0.003), log2-EASIX-d21 ([HR], 1.42; P<0.001),log2-EASIX-d28 ([HR], 1.66; P<0.001), log2-EASIX-d56 ([HR], 1.54; P<0.001)and log2-EASIX-d100 ([HR],1.83;P<0.001) were also found to be predictive of higher NRM. The most discriminating EASIX cut-off value before transplantation for risk of OS and NRM was 4.25 on the original scale(2.09 on the log2 scale). Patients with EASIX-PRE≥4.25 exhibited lower OS (2 years,24.3% vs 59.3%; P＜0.001) and higher NRM (2 years, 54.3%vs 24.5%; P=0.001) compared to patients with EASIX-PRE＜4.25.In multivariate analyses, we were able to validate the cut-off and found that EASIX-PRE≥4.25 was associated with more than threefold increased risk for OS(HR=3.72, 95%CI 1.74 to 7.94, p＜0.001)and NRM (HR=4.04, 95%CI 1.86 to 8.79,p＜0.001).Furthermore, EASIX-PRE≥4.25 was related to an increased risk of death from infection (HR=2.34, 95%CI 1.09 to 5.03,p=0.029). The occurrence of cGVHD was found to be associated with log2-EASIX-d0([HR], 0.82; P=0.039), log2-EASIX-d21([HR], 0.78; P=0.003) and log2-EASIX-d28([HR], 0.76; P=0.004) .Nevertheless, no correlation was observed between log2-EASIX at any time point and the occurrence of aGVHD and TA-TMA. EASIX is a readily accessible dynamic prognostic score that accurately predicts OS and NRM in elderly patients undergoing haploidentical HSCT at various time points.Notably, the optimal pre-transplantation EASIX cut-off value can be employed as a pre-transplantation assessment in elderly patients undergoing haploidentical HSCT, irrespective of the existing scoring system.