The role of tolerogenic cells in allogeneic haematopoietic stem cell transplantation

PAWSON, David Anthony (2021). The role of tolerogenic cells in allogeneic haematopoietic stem cell transplantation. Doctoral, Sheffield Hallam University.

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Abstract

Graft versus host disease (GvHD) is a complication of allogeneic haematopoietic stem cell transplantation (HSCT) which can result in significant patient morbidity and mortality. Recent advances in the understanding of the different types of immune cells, especially those that play a role in tolerance and immune regulation, has led to investigation of their role in transplant tolerance. These include: plasmacytoid dendritic cells (pDC), DC-10 cells and Type 1 regulatory T cells (Tr1). This study aims to determine any associations between tolerogenic cell populations including pDCs, DC-10 cells and Tr1 cells, along with other T cells, with the development of GvHD, and to analyse other allogeneic transplant outcomes including engraftment. It was postulated that there would be an inverse relationship between the number of tolerogenic cells and GvHD. In doing so, the study will determine if any or all of the analysed tolerogenic cells have the potential to be used as a biomarker for GvHD. 24 patients receiving transplants and five donors were consented and recruited onto the study between November 2018 and November 2019. The donors had their peripheral blood stem cell collection(s) and the recipients had their peripheral blood tested for: pDC, mDC1, DC-10, Tr1 and T cells at 2, 4, 8 weeks and 3 and 6 months post-transplant. Six patients were diagnosed with acute GvHD (aGvHD) and one patient was diagnosed with chronic GvHD within the 6-month follow up time period. There was no statistically significant difference between the patients diagnosed with GvHD versus those that were not with regards to graft CD34+ dose received (P = 0.68). There was no statistically significant difference between the patients who received a ‘high’ graft CD34+ dose versus those that received a ‘low’ CD34+ graft dose with respect to neutrophil (P = 0.7938) or platelet (P = 0.4197) engraftment. Chi-square analysis found no connection between GvHD diagnosis and the known risk factors for GvHD (P values ranging between 0.404 - >0.999). Patients diagnosed with GvHD had a similar mean age to those that were not, 54.83 years and 54.71 years respectively. Peripheral blood cell count data at the five post-transplant time points was split into GvHD and no GvHD groups and analysed using the Mann-Whitney test. No statistically significant difference was found between these groups, and the pDC, mDC1, DC-10, Tr1 and T cell counts at any time point (P values ranging between 0.077 - >0.999). The sample size in this study was small, and if the study was performed with a larger sample size then statistical significance may have been achieved. However, there was an overlap in cell counts between patients diagnosed with GvHD and those that were not, and without a separation of the cell counts between the GvHD and no GvHD groups, it would be difficult to determine a cut off value. An observation from the study was unusually high DC-10 cell counts prior to the diagnosis of GvHD in the one patient who died of GvHD. Further work is required to see if this finding is repeated.

Item Type:	Thesis (Doctoral)
Contributors:	Thesis advisor - Leyland, Rebecca
Additional Information:	Director of studies: Dr. Rebecca Leyland "No PQ harvesting"
Research Institute, Centre or Group - Does NOT include content added after October 2018:	Sheffield Hallam Doctoral Theses
Identification Number:	https://doi.org/10.7190/shu-thesis-00499
Depositing User:	Colin Knott
Date Deposited:	31 Jan 2023 15:26
Last Modified:	11 Oct 2023 12:32
URI:	https://shura.shu.ac.uk/id/eprint/31355

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