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T cell subsets and the outcome of haematopoietic stem cell transplantation

Prieto Hinojosa, AI; (2012) T cell subsets and the outcome of haematopoietic stem cell transplantation. Doctoral thesis , UCL (University College London). Green open access

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Abstract

Haematopoietic stem cell transplantation (HSCT) is an effective therapy for many malignant and non‐malignant diseases. However, adverse events such as infections, Graft‐versus‐Host Disease (GvHD) and relapse limit the wider use of HSCT. The identification of factors that predict the outcome of the transplant can be a vital tool to offer patients better options for treatment. Since there is a significant immunological contribution to the outcome of the transplant, it is of interest to ask to what extent the immune status of the patient prior to transplant might influence their subsequent recovery. After transplantation, the reconstitution of the T cell compartment in the patient relies on both expansion of existing T cells and the production of new ones via the thymus; in older patients this latter process is compromised by age‐dependent thymic involution. Improvements in thymus function leading to improvement in immune reconstitution after an HSCT may provide significant benefits, potentially reducing mortality from both infections and GvHD. In one study described in this thesis, an improvement in T cell reconstitution, in particular of the CD4 compartment, could be demonstrated after the administration of an LHRH agonist before transplantation from an allogeneic donor. Such an effect could not be demonstrated in an autologous setting. This may reflect a differential requirement for thymus function in the two transplant settings. In additional studies, various immune parameters including T cell subsets and cytokine profiles from the patient, that could affect the transplant outcome were analysed. The findings indicate that high levels of regulatory T cells (Tregs) as well as high levels of regulatory cytokines in patients pretransplant are factors that predict relapse after transplantation. It is likely that these act by suppressing anti‐tumour responses in the patient. These findings may provide a useful tool to stratify the patients into high and low risk categories prior to transplantation.

Type: Thesis (Doctoral)
Title: T cell subsets and the outcome of haematopoietic stem cell transplantation
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
URI: http://discovery.ucl.ac.uk/id/eprint/1355324
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