Pre-transplant inflammation and its associations with acute GvHD and mortality in pediatric allogeneic hematopoietic stem cell transplantation patients

Abstract

In this explorative study we aimed to identify inflammatory serum proteins measured before allogeneic hematopoietic stem cell transplantation (HSCT) that are associated with acute Graft-versus-Host Disease (aGvHD) and mortality in pediatric HSCT recipients. We measured 28 inflammatory serum proteins in 384 pediatric patients (2010-2022) with malignant (30%) and non-malignant (70%) indications for allogeneic HSCT. A sample before the start of the conditioning (T1) was included, as well as a sample on the day of HSCT (T2). For patients who developed aGvHD we also included a sample at the time of diagnosis, before initiation of systemic treatment (TP-GvHD). Associations with aGvHD, steroid-refractory aGvHD, non-relapse mortality (NRM) and overall survival (OS) were analyzed using robust (cause-specific) Cox models. At T1, TNFR1, sIL-2Rα and TNFR2 were among the most strongly associated proteins for the development of aGvHD. Multiple inflammatory proteins, such as CXCL16, TNFR1 and SCF at T1 were highly associated with NRM and OS. At TP-GvHD, ST2 levels were significantly associated with the development of steroid-refractory aGvHD and NRM. This study shows that inflammatory serum protein levels before HSCT are associated with aGvHD and mortality and lays the groundwork for further validation and use in risk-adapted therapy for pediatric HSCT recipients.