Search Results (12)

Chimeric antigen receptor-T (CAR-T) cell immunotherapy constitutes a cornerstone in the management of patients with relapsed/refractory B-cell lineage lymphoid malignancies. Toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematotoxicity (ICAHT) have been recognized in the post-infusion period. The initial interplay between CAR-T cells and tumor cells, followed by cytokine release and the bystander activation of the innate immunity cells, result in endothelial cell injury. In the current review, the ongoing research regarding endothelial injury in CAR-T cell recipients is summarized. Various markers of endothelial injury have been investigated in CAR-T cell recipients, including markers of complement activation, such as soluble C5b-9, endothelial dysfunction (angiopoietin-2, VCAM1, ICAM-1), inflammation, and thrombosis (von Willebrand antigen, ADAMTS13, thrombomodulin). The expression level of these endothelial injury markers has been identified as impaired in CAR-T cell recipients, not only when compared with healthy controls but also among patients with severe CRS/ICANS and those with mild toxicities or without toxicities. Furthermore, the Endothelial Activation and Stress Index (EASIX) and modified versions of this score, calculated in the pre- and early post-infusion period, seem to predict development of severe toxicities, ICAHT, and, thus, poor overall survival in CAR-T cell patients. More data concerning the role of these endothelial injury markers and clinical outcomes in CAR-T cell settings are essential. Full article

Objectives: Evaluation of the predictive potential of pre-CAR-T [¹⁸F]FDG PET/CT in Diffuse Large B-Cell Lymphoma (DLBCL) patients concerning Cytokine Release Syndrome (CRS) and Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS). Methods: Eighteen DLBCL patients (mean age: 60 ± 12 years) who underwent pre-therapeutic [¹⁸F]FDG-PET/CT and CAR-T cell therapy were retrospectively included. Median follow-up time was ten months (IQR6-16) after CAR-T cell infusion. Age, sex, serum lactate dehydrogenase (LDH), interleukin-6 (IL-6), C-reactive protein (CRP), and modified Endothelial Activation and Stress Index (mEASIX) were obtained. Potential occurrence of CRS/ICANS and the SUV_max were evaluated. Pearson and Spearman correlations, group comparisons (Mann–Whitney U-test) and the odds ratio (OR) were calculated. P values below 0.05 were defined as statistically significant and 95%-confidence intervals (CI) were calculated. Results: Pre-therapeutic SUV_max correlated positively with LDH (r = 0.5; p = 0.02), with the grade of CRS (r = 0.5; p = 0.03) and with the grade of ICANS (r = 0.6; p = 0.01). Appearance of ICANS was significantly correlated with pre-therapeutic SUV_max (p = 0.03; U = 7.0; Z = −2.2). Using ROC analysis and Youden’s index, an SUV_max threshold of 17 (AUC: 0.865; p < 0.01) was defined. Patients exceeding a pre-therapeutic SUV_max of 17 had a significantly higher risk of CRS grade > 1 (OR = 22; CI 2, 314; p = 0.03) and ICANS grade > 1 (OR = 18; CI 1, 271; p = 0.04). Conclusions: Pre-therapeutic SUV_max may be a useful marker for identifying DLBCL patients at risk for CRS and ICANS. Full article

Background/Objectives: Pancreatic cancer (PC) is an aggressive malignancy with a poor prognosis, frequently diagnosed at a metastatic stage. The identification of accessible, cost-effective prognostic biomarkers is critical for optimizing treatment strategies. The Endothelial Activation and Stress Index (EASIX), calculated using lactate dehydrogenase (LDH), creatinine, and platelet count, reflects endothelial dysfunction and has shown prognostic value in hematological cancers. However, its utility in metastatic PC remains unexplored. This study is the first to evaluate the prognostic significance of the EASIX in patients with metastatic PC receiving first-line FOLFIRINOX chemotherapy. Methods: This retrospective cohort study analyzed 204 patients diagnosed with metastatic pancreatic adenocarcinoma at Istanbul Training and Research Hospital between 2020 and 2025. All patients received FOLFIRINOX as first-line therapy. EASIX was calculated as LDH (U/L) × creatinine (mg/dL)/platelet count (10⁹/L). A cut-off value of 1.33 was used to stratify patients into low and high EASIX groups. Overall survival (OS) was assessed using Kaplan–Meier analysis and compared with the log-rank test. Results: The mean patient age was 63.0 ± 9.4 years; 61.8% were male. There were no significant differences in baseline characteristics between groups. Patients with EASIX ≥ 1.33 had significantly lower platelet counts and higher LDH and creatinine levels. Median OS was 14 months for EASIX < 1.33 and 8 months for EASIX ≥ 1.33 (p < 0.001). Conclusions: EASIX is a simple, inexpensive prognostic marker associated with overall survival in metastatic PC. Its integration into clinical practice may facilitate early risk stratification. Further prospective studies are needed to confirm its prognostic utility. Full article

Endotheliopathy plays an essential role in the pathophysiology of COVID-19. The endothelial activation and stress index (EASIX) indicates endothelial dysfunction. We aimed to investigate the relationship between a high EASIX score and mortality in patients with COVID-19. We retrospectively reviewed COVID-19 patients admitted to the ICU (intensive care unit) of the Ankara Bilkent City Hospital. We recorded hematological and biochemical parameters at the ICU admission and further calculated EASIX with the following equation: EASIX = Lactate dehydrogenase (U/L) × creatinine (mg/dL)/platelet count (10⁹/L). Statistical comparisons were made between the surviving and non-surviving groups in terms of EASIX. The median EASIX score was 1.2 (0.7–2.0) in the survivor group and a median of 2.5 (1.6–4.2) in the non-survivor group (p < 0.001). The mean log2-EASIX was 0.2 ± 0.9 in the survivor group and 1.3 ± 1.2 in the non-survivor group (p < 0.001). Lactate dehydrogenase, creatinine, Troponin I, D-dimer, procalcitonin, ferritin, and IL-6 were statistically significantly higher in the non-survivor group compared to the survivor group. The receiver operating characteristic (ROC) curve analysis showed that the cut-off value of the EASIX score was 2.05 (The area under the curve [AUC] = 0.764, p = 0.001, 95% CI: 0.662–0.847). Our study showed an association between high EASIX scores and poor prognosis in COVID-19 patients. Lactate dehydrogenase, creatinine, Troponin I, D-dimer, procalcitonin, ferritin, IL-6, EASIX, and log2-EASIX were statistically significantly higher in the non-survivor group compared to the survivor group. Being old and having chronic kidney disease increases the risk of death. Eventually, EASIX can be used to predict mortality in COVID-19 patients. Full article

Objectives: Risk stratification in coronary artery bypass grafting (CABG) remains challenging despite existing models. The Endothelial Activation and Stress Index (EASIX), originally developed for hematological conditions, has shown promise in various medical fields as a predictor of adverse outcomes. EASIX, calculated from lactate dehydrogenase, creatinine, and platelet count, reflects endothelial dysfunction and systemic inflammation. This study investigates EASIX’s potential in predicting mortality and morbidity in patients undergoing CABG. Methods: A total of 475 patients undergoing isolated CABG between January 2017 and June 2020 were retrospectively analyzed. EASIX scores were calculated from pre-operative blood samples. Patients were stratified based on an EASIX cut-off value of 1.16. Results: Patients with EASIX ≥ 1.16 were older and had more comorbidities. They experienced higher 30-day mortality (5.0% vs. 0.8%, p = 0.004), increased wound infections (6.7% vs. 2.5%, p = 0.035), and more frequent prolonged ventilation (9.2% vs. 4.2%, p = 0.040). The long-term survival analysis showed significant differences at 3 years (p = 0.030) and 5 years (p < 0.001). EASIX demonstrated moderate discriminatory power for long-term survival (AUROC 0.669, 95% CI: 0.598–0.740, p < 0.001). Importantly, the multivariable analysis revealed EASIX as an independent risk factor for long-term mortality, even after adjusting for traditional risk factors and comorbidities (HR: 2.65, 95% CI: 1.59–4.42, p < 0.001). Conclusions: EASIX ≥ 1.16 was associated with postoperative morbidity and poorer long-term survival in patients undergoing CABG. This easily calculable score could enhance risk stratification and guide personalized postoperative management. Full article

Introduction: Cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) are both serious complications of CAR-T therapy associated with endothelial dysfunction, prompting prior use of a modified version of the endothelial activation and stress index (m-EASIX) to predict the occurrence of severe ICANS and CRS. Previous studies have linked both hypophosphatemia and elevated IL6 levels to CRS and ICANS. Our study aimed to enhance the early prediction of both syndromes by integrating phosphorous and IL-6 both together and separately into the m-EASIX score. Methods: Forty-two patients with non-Hodgkin’s lymphoma presenting for CAR-T treatment were used to generate three variations in the m-EASIX score, assessing performance for the clinically actionable time points of day +0 through day +3. Results: The addition of phosphorous through the P-m-EASIX improved the predictive capabilities for the occurrence of ICANS, most notably on day +1 (AUC 89.6%; p = 0.0090, OR of 2.23; p = 0.0096) compared to the m-EASIX (AUC 80.8%; p = 0.0047, OR 1.72; p = 0.0046). The P-m-EASIX also showed enhanced predictive capabilities for the occurrence of CRS, with peak discriminatory function on day +3 (AUC 92.0%; p = <0.0001, OR 2.21; p = 0.0014). The addition of IL6 in the IL6-m-EASIX showed the highest discriminatory capacity for the prediction of CRS progression to grade ≥ 2 with peak function on day +3 (AUC 89.7%; p = 0.0040, OR 1.57; p = 0.031). Conclusions: Incorporating phosphorus levels into the m-EASIX score offered a cost-effective and straightforward method to improve the prediction of CAR-T toxicities. Larger-scale studies assessing the effectiveness of including phosphorus and IL-6 in the m-EASIX score to mitigate complications associated with CAR-T therapy are warranted. Full article

Background: Although the cure rates of classical Hodgkin Lymphoma (cHL) are as high as 90% using the current treatment protocols, the prognosis is poor for primary refractory patients. Thus, a biomarker that can predict patients with early progression at the time of diagnosis is an unmet clinical need. Endothelial activation and stress index (EASIX) and its variant modified EASIX (mEASIX) is a scoring system currently used for the prediction of prognosis in hematologic malignancies. This study aimed to investigate the prognostic value of the mEASIX score in newly diagnosed cHL patients. Methods: Data from 206 patients who underwent positron emission tomography (PET)-guided doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy for cHL between January 2007 and November 2023 were retrospectively analyzed. The prognostic value of the mEASIX score was evaluated using the receiver operating characteristic (ROC) analysis, Cox regression analysis, and the Kaplan–Meier method, and then compared with standard risk assessment methods. Results: The median age at diagnosis was 33 years, and the rate of patients in the advanced stage was 67%. ROC analysis determined an optimal mEASIX score cut-off of 17.28, categorizing patients into mEASIX^high (47%) and mEASIX^low (53%) groups. The 5-year progression-free survival (PFS) (60% vs. 84.3%) and overall survival (OS) (79.6% vs. 95.8%) were significantly lower in the mEASIX^high group (p < 0.001). Additionally, multivariate analysis showed that the independent variables affecting PFS included the nodular sclerosing subtype (HR: 0.4), bone marrow involvement (HR: 2.6), and elevated mEASIX (HR: 3.1). Independent variables, which had an effect on OS included elevated mEASIX (HR:3.8) and higher IPS-3 scores (HR:1.9). Furthermore, a higher mEASIX score (≥17.28) was identified as an independent variable indicating primary refractory disease (OR: 6.5). Conclusions: mEASIX is a powerful and easy-to-access marker for the detection of primary refractory disease and prognosis in newly diagnosed cHL cases. Full article

Endothelial injury indices, such as Endothelial Activation and Stress Index (EASIX), modified EASIX (m-EASIX), and simplified EASIX (s-EASIX) scores, have been previously associated with chimeric antigen receptor-T (CAR-T) cell immunotherapy complications. Soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor-15 (GDF-15), and soluble C5b-9 (sC5b-9) have been described as markers of endothelial injury post-hematopoietic stem cell transplantation. In the current study, we examined whether suPAR, GDF-15, and sC5b-9 levels were associated with endothelial injury indices in adult CAR-T cell recipients. The levels of these markers were measured in patients before CAR-T cell infusion and in healthy individuals with immunoenzymatic methods. We studied 45 CAR-T cell recipients and 20 healthy individuals as the control group. SuPAR, GDF-15, and sC5b-9 levels were significantly higher in the patients’ group compared to the healthy control group (p < 0.001, in all comparisons). SuPAR levels at baseline were associated with the m-EASIX scores calculated at the same time point (p = 0.020), while suPAR and GDF-15 concentrations were correlated with EASIX scores at day 14 post-infusion (p < 0.001 in both comparisons). Moreover, sC5b-9 levels were correlated with the s-EASIX scores at infusion (p = 0.008) and the EASIX scores at day 14 (p = 0.005). In our study, sC5b9, suPAR, and GDF-15 levels were found to reflect endothelial injury in CAR-T cell recipients. Full article

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can hamper the clinical benefit of CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (r/r LBCL). To assess the risk of CRS and ICANS, the endothelial activation and stress index (EASIX), the modified EASIX (m-EASIX), simplified EASIX (s-EASIX), and EASIX with CRP/ferritin (EASIX-F(C)) were proposed. This study validates these scores in a consecutive population-based cohort. Patients with r/r LBCL treated with axicabtagene ciloleucel were included (n = 154). EASIX scores were calculated at baseline, before lymphodepletion (pre-LD) and at CAR T-cell infusion. The EASIX and the s-EASIX at pre-LD were significantly associated with ICANS grade ≥ 2 (both p = 0.04), and the EASIX approached statistical significance at infusion (p = 0.05). However, the predictive performance was moderate, with area under the curves of 0.61–0.62. Validation of the EASIX-FC revealed that patients in the intermediate risk group had an increased risk of ICANS grade ≥ 2 compared to low-risk patients. No significant associations between EASIX scores and CRS/ICANS grade ≥ 3 were found. The (m-/s-) EASIX can be used to assess the risk of ICANS grade ≥ 2 in patients treated with CAR T-cell therapy. However, due to the moderate performance of the scores, further optimization needs to be performed before broad implementation as a clinical tool, directing early intervention and guiding outpatient CAR T-cell treatment. Full article

Acute-on-chronic liver failure (ACLF) is associated with high mortality. Objective prognostic scores are important for treatment decisions. EASIX (Endothelial Activation and Stress Index) is a simple biomarker consisting of LDH, platelets, and creatinine, reflecting endothelial dysfunction after allogeneic stem cell transplantation. Considering endothelial dysfunction in the pathogenesis of ACLF, this study aimed to test the discriminative ability of EASIX in advanced liver disease. We retrospectively analysed the prognostic potential of EASIX to predict 28-day and 3-month mortality in a total of 188 liver cirrhotic patients requiring treatment at the intensive care unit. We evaluated the ability of EASIX to rule out early infections and predict the need for hemodialysis. EASIX performed moderately better than established scores in predicting 28-day mortality (AUC = 0.771) and was nearly equivalent (AUC = 0.791) to SOFA and APACHE-II in the prediction of 3-month mortality. Importantly, EASIX showed better diagnostic potential in ruling out clinically apparent infections than common proinflammatory markers (AUC = 0.861, p < 0.001) and showed suitable accuracy in predicting the need for hemodialysis (AUC = 0.833). EASIX is an accurate, objective and easily assessable biomarker for predicting mortality and complications in patients with advanced liver disease. Full article

COVID-19 receives a lot of attention due to its threat to global public health. Research is ongoing to find universal methods to assess the baseline health status of a patient to determine prognosis and management strategies. This study aims to assess the predictive potential of the EASIX (Endothelial Activation and Stress Index) and two of its modifications (mEASIX and sEASIX) in terms of the need for admission to the ICU (intensive care unit), the use of IMV (invasive mechanical ventilation) and death due to COVID-19. The medical data of 370 severely ill patients hospitalised in the COVID-19 departments of the Regional Specialist Hospital in Wroclaw (Poland), including the ICU, were analysed retrospectively. The mortality rate in the group studied was 65.7% (243 cases). In the case of all three indices, EASIX, mEASIX and sEASIX, there was a statistically significant correlation between the need for admission to the ICU (p = 0.026, p = 0.019, p = 0.001, respectively) and the risk of death (p < 0.001). In terms of the risk of death, the high values of the assessed indices (EASIX ≥ 2.36, mEASIX ≥ 704.03, sEASIX ≥ 3.81) were characterised by low sensitivity (≤40%), high specificity (approximately 90%) and low NPV (negative predictive value) (approximately 40%) with high PPV (positive predictive value) (approximately 80%). Due to the ease of implementation and the low cost of performing basic laboratory tests, the above-mentioned indices can be used as an additional, but not universal tool for the initial assessment of the health condition of patients admitted to the hospital. Full article

COVID-19, as a disease involving the endothelium of multiple organs, is characterized by high mortality rates among hospitalized patients. Patients with hematological malignancies are particularly at risk of an unfavorable course of COVID-19. The endothelial activation and stress index (EASIX) score has been used as a simple predictor of overall survival (OS) in specific groups of hematological cancer patients. EASIX, as a biomarker of endothelial dysfunction, might play a prognostic role in patients with COVID-19. Here, we performed a comprehensive retrospective analysis of the EASIX score in 523 hospitalized COVID-19 patients with or without coexisting hematological cancer. Hematological cancer COVID-19 patients had higher EASIX scores compared to the overall population with COVID-19. In hematological patients, EASIX was a strong predictor of the occurrence of sepsis during COVID-19. Our findings demonstrated EASIX as a strong predictor of intensive care unit admission, in-hospital mortality, the occurrence of acute renal failure and the need for hemodialysis, both in hematological and non-hematological COVID-19 patients. Patients with a high EASIX score on COVID-19 diagnosis had significantly inferior OS compared to patients with low EASIX. We showed for the first time that EASIX might serve as a simple, universal prognostic tool of OS in both hematological and non-hematological COVID-19 patients. Full article