Nikolajeva, O; (2017) Factors Influencing The Provision And Clinical Usage Of Umbilical Cord Blood Units As A Graft Source In Unrelated Haematopoietic Stem Cell Transplantation. Doctoral thesis , UCL (University College London).

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Abstract

Hematopoietic stem cell transplantation (HSCT) is currently used as a potential curative therapy for several malignant and non-malignant disorders. In recent years our understanding of complexity of immunogenetics of HSCT has led to new indications for the procedure. Therefore the demand for unrelated hematopoietic stem cell (HSC) donors keeps rising. HLA matching remains the main determining factor when searching for an HSC donor. An HLA-identical sibling still remains the most suitable donor, but only around 30% of patients (requiring HSCT) have this option. Others require a search for an alternative donor. Because the HLA system is highly polymorphic, the chance of finding a suitable matched unrelated donor is limited. When bone marrow or peripheral blood are used as source of HSC, stringent HLA-matching is required to lower the risk of transplant-related complications. The donor pool is especially limited for patients with diverse racial and ethnic backgrounds because such ethnicities are underrepresented on current worldwide donor registries (Barker, Byam, et al., 2010). To overcome this problem, unrelated umbilical cord blood units (UCB) can be selected as readily available alternatives for patients who lack both HLA-matched siblings and suitable unrelated donors. This thesis provides an insight into the contemporary factors influencing selection of unrelated umbilical cord blood (UCB) for transplantation. Studies in this thesis provide a detailed analysis of current UCB selection practice and explore new factors that can help to develop a patient tailored approach to the UCB selection process. Work is based on the understanding of a tri-dimensional donor-recipient interaction process in the context of UCBT, which involves not only direct donor-recipient interaction, but also involves foeto-maternal exchange of information. My key finding was that maternal characteristics (i.e. previous pregnancy and exposure to infections) influence quality characteristics of UCB and potentially have an impact on transplant outcomes. Based on my study findings, a new project has been initiated. It will study a larger cohort of patients and investigate the impact of birth order and previous child’s sex on UCBT outcome.

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