Elevated high-density lipoprotein levels following acute graft-versus-host disease onset: a potential link to T-cell dysfunction and increased relapse risk.

Objectives: Allogeneic stem cell transplantation (allo-SCT) is the only curative treatment option for several haematologic malignancies. Its therapeutic principle is based on the donor T cells' ability to eliminate any residual malignant cells. Despite its success, challenges such as graft-versus-host disease (GvHD) and disease relapse persist. Recent studies emphasise the role of the metabolic environment in shaping T-cell responses. This study investigates the impact of serum metabolites on T-cell responses following allo-SCT. Methods: Metabolite levels in serum samples from 55 allo-SCT patients transplanted between November 2015 and October 2018 were analysed by nuclear magnetic resonance (NMR) spectroscopy for six time points after transplantation. These metabolite profiles were correlated with clinical data and T-cell characteristics obtained by flow cytometry-based immunomonitoring. High-density lipoprotein (HDL) emerged as a key factor of interest. To explore the potential relationship between T-cell-related differences and HDL levels, healthy donor T-cell cultures supplemented with HDL were performed. Results: Elevated HDL levels were associated with acute GvHD (aGvHD) and relapse. Patients with high HDL serum levels exhibited a delayed normalisation of T-cell frequencies and increased effector-memory CD8 Conclusions: AGvHD was linked to elevated HDL levels, potentially affecting T-cell-mediated graft-versus-leukaemia (GvL) activity and promoting relapse. HDL could therefore be a potential biomarker for the success of allo-SCT and a lever for improving patients' outcomes.