Aim
Poor graft function (PGF), characterised by persistent multilineage cytopenias, is a life-threatening condition following allogeneic haematopoietic stem cell transplantation (alloHSCT). Whilst the role of bone marrow immunity in PGF has been previously described, little has been said about peripheral immunity. In this study, the role of the peripheral immunity in PGF was investigated, providing a deeper understanding of the immune system and its contributions to PGF. The secondary aim was to assess the efficacy of combined Atorvastatin (AT) and N-Acetyl-Cysteine (NAC) treatment in PGF patients.
Methods
Peripheral blood mononuclear cells (PBMCs) were collected from sex- and age-matched PGF patients, GGF patients, and healthy donors (HD) provided by The Australian Red Cross Blood Service (n=10/group). Using a 31-plex flow panel, immune cell subsets were identified and compared across the three groups. T cell function was assessed using combined degranulation and intracellular staining assay. Patients with PGF were treated with combined AT and NAC as part of the RESELECT trial (ACTRN12620001339943), and timepoints post-treatment were analysed. Samples were acquired using a Cytek Aurora flow cytometer. Analysis was performed using FlowJo and PRISM software.
Results
Preliminary findings show increased proportions and overactivation of CD8+ and CD4+ naive T cells with elevated levels of degranulation and tumour necrosis factor (TNF) production in patients with PGF compared to GGF and HD. Further, both CD8+ and CD4+ T effector memory and effector memory CD45RA+ T cells were impaired in patients with PGF. Treatment with AT and NAC shows some improvement in normalising CD8+ and CD4+ T cell subset degranulation levels.
Summary
The preliminary findings of this study provide valuable insight into patient peripheral immunity in PGF, and the immunological changes that occur with combined AT and NAC treatment.
Conflicts of Interest
No conflict of interest to disclose.