EASIXd0 Predicts Early Transplant-Related Mortality in Patients Undergoing Haploidentical Transplantation with Post-Transplant Cyclophosphamide-Mycophenolate Mofetil-Based GvHD Prophylaxis
Authors: Pai Aswin Anand , Parthiban Nieshanth , Bijukumar Nayanthara , Renji Rachel Mariam , A Manoj , Karumathil Sujith , Lakshmi Kavitha M , Selvarajan Sushil , Korula Anu , NA Fouzia , Abraham Aby , Srivastava Alok , Mathews Vikram , George Biju , Kulkarni Uday , Balasubramanian Poonkuzhali 
Published: December 2024

Haploidentical Stem Cell Transplantation (HaploHCT) with Post-transplant Cyclophosphamide (PTCy) based Graft versus Host disease (GvHD) prophylaxis has improved the success of treatment for several hematological disorders when a matched donor is not available. However, there is still a significant heterogeneity in clinical outcomes and high Transplant-related Mortality (TRM). Endothelial damage is an important factor in early complications following HaploHCT, contributing to increased TRM. The Endothelial Activation and Stress Index (EASIX) was developed to address the need for predictive tools in clinical practice, utilizing routine laboratory parameters such as creatinine, lactate dehydrogenase (LDH), and thrombocyte counts. We previously identified pre-HCT EASIX score as a prognostic biomarker for TRM in patients with class III thalassemia undergoing HCT (Kulkarni et al. Blood, 2021). The present study aimed to evaluate the EASIXd0 score in predicting early TRM in patients with different hematological disorders undergoing HaploHCT.

Eighty patients with various underlying diagnoses who underwent HaploHCT between October 2021 and March 2023 were enrolled. All patients received uniform GvHD prophylaxis comprising PTCy (I.V. 50 mg/kg/day x 2 days (day +3 to day +4) and i.v. Cyclosporine A (CsA) (2.5mg/kg, Q12H) with oral Mycophenolate Mofetil (MMF) (15 mg/kg/dose Q8H) from day +5 post-HCT. Baseline demographic information, clinical and laboratory data, and details of transplantation, including donor characteristics, were retrieved from the electronic medical records. The EASIXd0 score was calculated as (serum LDH (U/L) x serum creatinine (mg/dL))/platelet count (x 10^9 /L) using laboratory data recorded on the day of HCT (day 0). The calculated EASIXd0 scores were then tested to predict early TRM (Day+30), TRM (Day+100), and 1-year Overall Survival (OS).

The median patient age was 21 (1 to 59), and 53 (66.3%) were males. 53 (66.3%) patients were undergoing HaploHCT for hematological malignancies. All received peripheral blood stem cell grafts, of which 47 (58.8%) patients received myeloablative conditioning before HCT. The median EASIXd0 score was 1.14, ranging between 0.16 and 21.73. Thirteen (16.3%) patients had TRM+30, thirty-one (38.8%) patients had TRM+100 and the 1-year OS was 48.7%. The major causes of early deaths (day 30 and day 100) were Infections (61%), GvHD (13%), and regimen-related toxicities (16%). The median EASIXd0 score was significantly higher among patients with TRM+30 (4.95 vs. 0.97, p=0.01) and TRM+100 (3.12 vs. 0.93, p=0.03).

Further analysis revealed that the cumulative incidence of TRM at 30 days was 25% for the patients with above the median EASIX d0 (&gt;1.14) score compared with 7% for those with below the median EASIX d0 score (p=0.03). Similarly, the cumulative incidence of TRM at 100 days was 52% for the patients with above the median EASIX d0 (&gt;1.14) score compared with 25% for those with below the median EASIX d0 score (p=0.01).We then tested other risk factors, including post-HCT factors, that could impact TRM; only non-engraftment of neutrophils and platelets impacted TRM at both 30 and 100 days significantly (p&lt;0.001). Further, regression analysis revealed that a high EASIXd0 score &gt;1.14 was associated with high TRM+30 (HR=4.11; 95%CI=1.04-16.29; p=0.04).

Our study suggests that the EASIXd0 score can identify patients at greater risk for early TRM in patients undergoing haploHCT. Further studies are ongoing to validate our findings in a larger prospective cohort of patients undergoing HaploHCT with PTCy/CsA/MMF-based GvHD prophylaxis to test the clinical utility of EASIXd0 score as a prognostic biomarker for HaploHCT.