The Impact of Treosulfan -based Conditioning for Inborn Errors of Immunity: Is Dose Monitoring Crucial?

Abstract In children with inborn errors of immunity (IEI) who receive a hematopoietic stem cell transplant (HSCT), treosulfan-based conditioning is currently preferred. This study aimed to investigate early and late outcomes and examine the effect of treosulfan dose monitoring on outcomes. Seventy-three pediatric patients receiving this management between 2015 and 2022 were included. Overall survival rate was 80%, and event-free survival was 67.8%. A larger treosulfan dose AUC increased the rate of early toxicity (p=0.034) and slowed lymphocyte engraftment (r=0.290; p=0.030). Underlying disease, treosulfan AUC, donor type, stem cell type, number of immunosuppressive agents, the dose of anti-thymocyte globulin, and post-transplantation cyclophosphamide did not increase acute graft-versus-host disease. The risk of mixed chimerism (MC) in patients with autoimmune lymphoproliferative syndrome and leukocyte adhesion deficiency was higher than those with severe combined immunodeficiency (p=0.021 and p=0.014, respectively). The risk of MC was lower in those receiving peripheral blood stem cells (SC) compared with bone marrow-derived SC (OR=0.204, p=0.022). The AUC of treosulfan dose was not associated with poorer late outcomes. Treosulfan is an agent that can be used safely in the IEI patient group; level measurement appears essential to identify early toxicities. Prospective studies with more extended follow-up periods are needed.