Pretransplantation EASIX predicts intensive care unit admission in allogeneic hematopoietic cell transplantation

Abstract

The Endothelial Activation and Stress Index (EASIX) is a laboratory-based prognosis index defined as creatinine × lactate dehydrogenase/platelets. When measured at pretransplantation evaluation (EASIX-PRE), it predicts allogeneic hematopoietic cell transplantation (alloHCT) mortality. This study explores its ability to predict intensive care unit (ICU) admission and validates EASIX-PRE predictive power for overall survival (OS) and nonrelapse mortality (NRM) in 167 consecutive patients undergoing alloHCT. EASIX-PRE was calculated retrospectively in all patients and transformed into log2 values (log2-EASIX-PRE). Log2-EASIX-PRE predicted ICU admission (hazard ratio [HR], 1.41; P < .001), OS (HR, 1.19; P = .011), and NRM (HR, 1.28; P = .004). The most discriminating EASIX-PRE cutoff value for risk of ICU admission was the 75th percentile (2.795); for OS and NRM, it was the median value (1.703). Patients with EASIX-PRE >2.795 had higher incidence of ICU admission in comparison with patients with lower EASIX-PRE values (day +180, 35.8% vs 12.8%; HR, 2.28; P = .010). Additionally, patients with EASIX-PRE >1.073 had lower OS (2 years, 57.7% vs 68.7%; HR, 1.98; P = .006) and higher NRM (2 years, 38.7% vs 18.5%; HR, 2.92; P = .001) than patients with lower EASIX-PRE results. Log2-EASIX-PRE was not associated with incidence of transplantation-associated microangiopathy, sinusoidal obstruction syndrome, or acute graft-versus-host disease. This study proposes EASIX-PRE as a prognostic tool to identify patients undergoing alloHCT at increased risk of severe organ dysfunction and who would therefore require ICU admission. Early identification of patients at high risk of severe events could contribute to personalized intervention design. Additionally, it validates the association between EASIX-PRE and OS and NRM in those undergoing alloHCT.

Early vascular endothelial complications after hematopoietic cell transplantation: Role of the endotheliopathy in biomarkers and target therapies development

“…Lastly, the Endothelial Activation and Stress Index (EASIX) was developed as a biomarker-based laboratory formula defined as creatinine (mg/dL) x lactate dehydrogenase (LDH; U/L)/platelets (x 109/L) to predict mortality in patients with aGVHD ( 149 ). EASIX, when measured at different time points before and after the stem cell infusion, has additionally been shown to be useful for the prediction of mortality after allo-HCT ( 150 ), TA-TMA ( 150 ), ICU admission ( 151 ), and SOS ( 123 ). Moreover, a modified version of EASIX, which substitutes creatinine for C reactive protein, demonstrated predictive utility for CRS and ICANs in CAR-T cell patients ( 152 , 153 ).…”

Von Willebrand factor as a potential predictive biomarker of early complications of endothelial origin after allogeneic hematopoietic stem cell transplantation

“…Sepsis, VOD and acute GVHD have also physiological roots in endothelial activation 6,33 . Although the EASIX score is nowadays validated both in the pre-alloHCT evaluation and at the onset of acute complications of cellular therapies 13,14,27,34 , there is still a lack of speci c biomarkers for endothelial dysfunction 19 . Serum markers of endothelial cell distress such as nitrates, angiopoietin-2, interleukin-18, asymmetric dimethyl arginine or neutrophil extracellular traps are sometimes proposed 2,19,35,36 , but are not available in routine practice.…”

“…Regarding endothelial dysfunction after alloHCT, the EASIX score has been developed to re ect a certain degree of endothelial vulnerability. It incorporates routine and easily available biological markers and has been shown to be prognostic for acute GVHD, sepsis and death after alloHCT [12][13][14] .…”

Diagnosis and management of endothelial disorders following haematopoietic stem cell transplantation

“…Later iterations of the EASIX score included measurement at pretransplant evaluation (EASIX-PRE), which resulted in the prediction of allo-HSCT OS, nonrelapse mortality, TA-TMA and intensive care unit admission. 12 However, the utility of EASIX in the EIS setting, beyond a predicted risk for TA-TMA, has not been established. Hence, there is limited value in the addition of this prognostic score in the context of already well-established alternatives such as the European Group for Blood and Marrow Transplantation (EBMT) score and Haematopoietic Cell Transplantation -Comorbidity Index (HCT-CI) for OS in allo-HSCT.…”

“…Later iterations of the EASIX score included measurement at pretransplant evaluation (EASIX‐PRE), which resulted in the prediction of allo‐HSCT OS, nonrelapse mortality, TA‐TMA and intensive care unit admission 12 . However, the utility of EASIX in the EIS setting, beyond a predicted risk for TA‐TMA, has not been established.…”