Dynamic-EASIX DRI Model: A Novel Tool for Predicting Outcomes After Allogeneic Hematopoietic Cell Transplantation.

Post-transplant cyclophosphamide (PTCy) has emerged as the standard graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic stem cell transplantation (alloHCT). The Endothelial Activation and Stress Index (EASIX) has been shown to be a key determinant of post-transplant outcomes, yet the dynamic trends of post-transplant EASIX scores across GVHD prophylaxis platforms and its prognostic utility remain incompletely defined. We evaluated longitudinal post-transplant EASIX score trajectories in patients receiving PTCy versus calcineurin inhibitor/methotrexate (CNI/MTX)-based prophylaxis and developed an individualized dynamic risk model for post-transplant survival. Log2-EASIX scores from day +20 to day +120 were evaluated using dynamic landmark analysis and combined with the pre-transplant disease risk index (DRI) to develop a dynamic-EASIX DRI risk prediction model which could predict post-transplant mortality. Patients were randomly segregated in a 2:1 ratio into training and validation cohorts to develop and validate the model, respectively. A total of 534 alloHCT recipients were evaluated, of whom 150 (28.1%) received PTCy. In the training cohort, an increasing log2-EASIX score (HR 1.44, P = 0.001) and an increasing log2-EASIX trend/slope (HR 2.81, P = 0.002), both were associated with an inferior 1-year overall survival (OS). The dynamic-EASIX DRI model had a C-index of 0.82 for 1-year and 0.84 for 2-year survival. In the validation cohort, the area under curve for the dynamic-EASIX DRI model was 70.2% and 75.4% for 1 and 2-yr OS, respectively. The dynamic-EASIX DRI model is a novel tool that can be used to risk stratify patients in the post-transplant follow-up period and can be applied irrespective of GVHD prophylaxis.