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Immune reconstitution in cord blood transplantation

Devlia, Vikesh; (2018) Immune reconstitution in cord blood transplantation. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Umbilical cord blood (UCB) is a readily available option as a stem cell source for those requiring an allogeneic transplant as part of curative therapy for malignant or non-malignant haematological disorders. Immune reconstitution is essential in cord blood transplant (CBT) patients to reduce the development of post-transplant complications. The kinetics and diversity of reconstituting immune cells has not been comprehensively investigated in CBT patients within the UK. Thus, in this study the kinetics and diversity of reconstituting immune cell subsets within CBT patients in the UK has been analysed. CBT patients provided whole blood samples at 28, 60, 100, 180, 365 and 720 days post-CBT. Flow cytometry was used to determine the kinetics and diversity of reconstituting immune cells. T-cell receptor excision circles (TRECs) and kappa deleting recombination excision circles (KRECs) were quantified using Real Time PCR (RT-PCR) to measure thymic and bone marrow output. NK cell function was determined through immunophenotyping of stimulatory and activating markers and cytotoxicity directed to K562 cells. CD45+ cells and CD14+ monocytes reconstitute by 60 days post-CBT. CD19+ B cells reconstitute by 100 days and a higher absolute count of CD19+ B cells at 28 days post-CBT correlates with improved overall survival. T cell reconstitution is delayed for up to 720 days for CD3+/CD4+ T cells and 365 days for CD8+ T cells. Thymic output is delayed for up to 720 days with low absolute levels of naïve T cells and low TREC copy numbers. However, increased numbers of effector memory T cells demonstrate thymic independent expansion of T cells. NK cells are activated, producing IFN- and mount a cytotoxic response towards K562 cells. Therefore, this project provides an insight into the kinetics and diversity of reconstituting immune cell subsets in CBT patients, serving as a timeline that can be used clinically.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Immune reconstitution in cord blood transplantation
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2018. Original content in this thesis is licensed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) Licence (https://creativecommons.org/licenses/by/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL > Provost and Vice Provost Offices
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: https://discovery.ucl.ac.uk/id/eprint/10062364
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