Establishment of a predictive model for GVHD-free, relapse-free survival after allogeneic HSCT using ensemble learning

Graft-versus-host disease-free, relapse-free survival (GRFS) is a useful composite end point that measures survival without relapse or significant morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to develop a novel analytical method that appropriately handles right-censored data and competing risks to understand the risk for GRFS and each component of GRFS. This study was a retrospective data-mining study on a cohort of 2207 adult patients who underwent their first allo-HSCT within the Kyoto Stem Cell Transplantation Group, a multi-institutional joint research group of 17 transplantation centers in Japan. The primary end point was GRFS. A stacked ensemble of Cox Proportional Hazard (Cox-PH) regression and 7 machine-learning algorithms was applied to develop a prediction model. The median age for the patients was 48 years. For GRFS, the stacked ensemble model achieved better predictive accuracy evaluated by C-index than other state-of-the-art competing risk models (ensemble model: 0.670; Cox-PH: 0.668; Random Survival Forest: 0.660; Dynamic DeepHit: 0.646). The probability of GRFS after 2 years was 30.54% for the high-risk group and 40.69% for the low-risk group (hazard ratio compared with the low-risk group: 2.127; 95% CI, 1.19-3.80). We developed a novel predictive model for survival analysis that showed superior risk stratification to existing methods using a stacked ensemble of multiple machine-learning algorithms.