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Strategies to Improve Haematological Reconstitution Post-Allogeneic Haematopoietic Stem Cell Transplantation

Cuadrado Collados, Maria Del Mar; (2023) Strategies to Improve Haematological Reconstitution Post-Allogeneic Haematopoietic Stem Cell Transplantation. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

A correct immune reconstitution is crucial for a successful allogeneic haematopoietic stem cell transplantation (allo-HCT). This thesis explores different ways of improving immune reconstitution focusing on three major complications: Graft failure (GF); Poor graft function (PGF); and Relapse. GF is an infrequent but devastating complication after allo-HCT. With the introduction of haploidentical and umbilical cord blood (UCB) transplants, the study of donorspecific HLA allo-antibodies (DSAs) has acquired more prominence as a potential cause, and clinical guidelines about how to manage patients in this setting have been developed. However, not many studies have been performed in the unrelated donor setting and no consensus has been established on how to act when DSAs are present. To address this question, one of the chapters in this thesis studies the impact of DSAs on GF through a retrospective study with cases collected from the Anthony Nolan Research Institute Database. PGF is also an infrequent but life threatening complication after allo-HCT. CD34+ selected stem cells has been established as a treatment for PGF; but the studies published on it have featured low numbers of patients and heterogeneity in the definitions of PGF or response criteria. The second chapter in this thesis looks to rectify these deficiencies by analysing the efficacy and predictors of response of this approach through a retrospective study that included the data of 62 patients. The final chapter focuses on disease relapse and explores a new way of delivering donor lymphocytes infusion (DLI) prophylactically, through a clinical trial. This clinical trial, studies the effect of manipulated CD8+ T depleted DLI in the related donor transplant setting and its impact on progression free survival. It also studies other factors such as the rates of conversion to full donor chimerism and the effects of immune reconstitution in non-relapse mortality (NRM) and overall survival (OS).

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Strategies to Improve Haematological Reconstitution Post-Allogeneic Haematopoietic Stem Cell Transplantation
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/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 > 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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10184438
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