Ros Soto, Jose; (2021) Vitamin D and Immune Responses in Haematopoietic Stem Cell Transplantation. Doctoral thesis (M.D(Res)), UCL (University College London).

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Abstract

Among its pleiotropic effects, vitamin D has immunoregulatory properties that help to maintain immune homeostasis. Multiple factors make haematopoietic stem cell transplant (HSCT) recipients at higher risk of vitamin D deficiency, and this (even prior to the stem cell infusion) can impact adversely over the course of HSCT. Owing to the lack of consensus, a cut-off to define vitamin D deficiency has not been established yet and clinical practice may vary across different HSCT units. To address this, one of the chapters of this thesis has examined the current management of vitamin D deficiency in the allogeneic HSCT setting, confirming the highly heterogeneous practice across the EBMT affiliate centres, including those from diverse geographical locations and dedicated to patients from different age. Graft-versus-host disease (GvHD) is a major cause of morbidity and mortality after allogeneic HSCT. To confirm or rule out this disease, a biopsy result from the affected tissue may be delayed for several days or even weeks. GvHD biomarkers are promising diagnostic tools that can speed up this process, predict outcomes in the early post-HSCT phase and monitor response to immunosuppression, minimising the detrimental effect of this therapy on HSCT recipients. Due to this, an observational study will explore the role of three of these biomarkers (elafin, REG3α and ST2), alongside vitamin D, in the context of patients with acute and chronic GvHD on immunosuppressive therapy. The final study moves away from vitamin D and biomarkers although it is still linked to the graft-versus-host reaction. Infusion of donor lymphocytes (DLI) is an effective adoptive immunotherapy that approximately 25% of post-HSCT patients have received in the UK1. DLI enhances graft-versus-leukaemia effect but its main side effect is GvHD. This chapter describes a single-centre experience treating 100 patients with DLI after reduced intensity conditioning (RIC) HSCT for mixed chimerism (MC) or relapse of the primary disease. It aims to determine factors implicated in achieving full donor chimerism (FDC) or disease remission, as well as their impact on other outcomes post-DLI, such as survival, relapse post-DLI or GvHD, in order to improve survival and quality of life in these patients. We found that patients with younger donors were less likely to develop acute GvHD and subsequently it contributed to a greater survival, which has been previously reported in HSCT recipients but never in those receiving subsequent DLI.

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