P1369: PRETRANSPLANT MODIFIED ENDOTHELIAL ACTIVATION AND STRESS INDEX (M-EASIX-7): A PREDICTOR OF PROGNOSIS IN ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION

Abstract

Background: Endothelial damage is considered to be the major underlying mechanism in the physiopathogenesis of transplant related complications including graft versus host disease (GVHD), thrombotic microangiopathy (TMA), sinusoidal obstruction syndrome (SOS) and sepsis. A novel scoring index, Endothelial Activation and Stress Index (EASIX), is a simple method consisting of endothelial activation parameters, which was indicated to predict GVHD and posttransplant survival. Similarly, modified EASIX (mEASIX) is a marker of endothelial dysfunction and has been shown to be associated with the development of cytokine release syndrome after CAR-T cell therapy. Aims: In this study, we investigated the role of EASIX and mEASIX scores in the prediction of transplant related complications and survival in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHCT). Methods: A total of 398 alloHCT recipients [median age: 43(17-71) years; male/female: 243/155] were included in this retrospective study. EASIX [lactate dehydrogenase (U/L) x creatinine (mg/dl) / platelets (109/L)] and mEASIX [lactate dehydrogenase (U/L) x C reactive protein (CRP) (mg/dl) / platelets (109/L)] scores were calculated on days -7, 0, +3 and +7. Statistical analysis was performed based on log2 transformed values. Patient and transplant characteristics are summarized in Table 1. Results: Median follow-up time was 573.5 (4-3877) days. Probability of OS was estimated to be 35.1% (1343 ± 351.7; 95% CI: 653.6-2032.3), while the probabilities of day-30 mortality, day-100 mortality and NRM were 6%, 12.5% and 49% respectively. In multivariate analysis EBMT score (p=0.026, HR: 1.177; 95% CI: 1.019-1.359), CRP (p=0.033, HR: 1.004; 95% CI: 1.000-1.008), EASIX-7 (p=0.042, HR: 0.182; 95% CI: 0.035-0.941) and mEASIX-7 (p=0.016, HR: 2.668; 95% CI: 1.202-5.924) were found to have significant impact on OS. The predictive effect of mEASIX-7 was confirmed for day-30 mortality (p=0.038; HR: 1.7; 95% CI: 1.030-2.805). A positive correlation was demonstrated between mEASIX-7 and SOS (p=0.013; r=0.249). On the other hand, mEASIX+7 was found to have a significant impact on the development of engraftment syndrome (p=0.028; HR: 1.403; 95% CI: 1.038-1.896), EASIX+3 on TMA (p=0.027; HR: 2.361; 95% CI: 1.100-5.066) and mEASIX0 on TMA (p=0.011; HR: 2.209; 95% CI: 1.199-4.068). Based on the optimal cutoff value of mEASIX-7 for the prediction of day-30 mortality, which was determined to be 2.71 [AUC: 0.747 (0.599-0.896);p=0.021], the study group was divided into two subgroups as low-mEASIX-7 and high-mEASIX7 groups. Probability of OS was significantly higher in the low-mEASIX-7 group compared to high-mEASIX-7 group (37% vs 25.2%; p=0.008; HR: 2.057; 95% CI: 1.208-3.504). Day-30 mortality (2.9% vs 19.4%; p=0.017; HR: 7.028; 95% CI: 1.418-34.836) and day-100 mortality (9% vs 33%; p=0.004; HR: 4.469; 95% CI: 1.619-12.336) were significantly lower in the low-mEASIX-7 group. Furthermore, the probability of NRM was significantly lower in the low-mEASIX-7 group compared to high-mEASIX-7 group (44.8% vs 61.4%; p=0.005; HR: 2.551; 95% CI: 1.318-4.941). Image:Summary/Conclusion: Pretransplant risk assessment is essential to guide the mainstays of the transplant procedure and optimize supportive care measures. In consideration with the basic role of endothelial activation in the development of life threatening complications of alloHCT, mEASIX-7 is indicated to have a predictive prognostic impact on survival and transplant related complications.