Development and Validation of a Concise Objectifiable Risk Evaluation Score for Non-Relapse Mortality after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

We aimed to develop a concise objectifiable risk evaluation (CORE) tool for predicting non-relapse mortality (NRM) and overall survival (OS) after allogeneic hematopoietic stem cell transplantation (allo-HCT). A total of 1120 adult patients who had undergone allo-HCT at our center between 2013 and 2020 were divided into training, first, and second validation cohorts. Objectifiable, patient-related factors impacting NRM in univariate and multivariate analyses were: serum albumin, serum creatinine, serum C-reactive protein (CRP), heart function (LVEF), lung function (VC, FEV1), and patient age. Hazard ratios were assigned points (0–3) based on their impact on NRM and summed to the individual CORE HCT score. The CORE HCT score stratified patients into three distinct low-, intermediate-, and high-risk groups with two-year NRM rates of 9%, 22%, and 46%, respectively, and OS rates of 73%, 55%, and 35%, respectively (p < 0.001). These findings were confirmed in a first and a second recently treated validation cohort. Importantly, the CORE HCT score remained informative across various conditioning intensities, disease-specific subgroups, and donor types, but did not impact relapse incidence. A comparison of CORE HCT vs. HCT Comorbidity Index (HCT-CI) in the second validation cohort revealed better performance of the CORE HCT score with c-statistics for NRM and OS of 0.666 (SE 0.05, p = 0.001) and 0.675 (SE 0.039, p < 0.001) vs. 0.431 (SE 0.057, p = 0.223) and 0.535 (SE 0.042, p = 0.411), respectively. The CORE HCT score is a concise and objectifiable risk evaluation tool for adult patients undergoing allo-HCT for malignant disease. External multicenter validation is underway.