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Title: Flow cytometry for monitoring the response to chemotherapy in low grade B-cell disorders
Author: Thaci, Louise Ann
Awarding Body: Ulster University
Current Institution: Ulster University
Date of Award: 2013
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Low Grade B-cell Disorders (LO-BCDs) have been found to be formed from B cells with clonal proliferations arising as B cells differentiate. There are 5 main groups of particular interest in this research project: Chronic Lymphocytic Leukaemia (CLL), Follicular Cell Lymphoma (FCL), Low Grade Lymphoma - unspecified (LOL) Mantle Cell Lymphoma (MCL) and Multiple Myeloma (MM). Currently, bone marrow analysis provides clear indication of relapse, though the procedure is invasive. Immunophenotyping of peripheral blood can identify minute numbers of T cells involved in the pathogenesis of relapse and is non-invasive. This study aimed to investigate which T cells were present and whether the methods employed could be used to replace the need for bone marrow analysis to confirm infection and relapse. The literature review provides an overview of normal cell development and the production of neoplastic cells that develop into LG-BCDs. A brief review of the chemotherapy treatments available is discussed and the methods of diagnosis, and confirmation of the disorders, including an introduction to flow cytometry is given. The preparation of controls, antibodies and reagents used in the study were validated according to good scientific practice and a reliable standard operating procedure for analysis was generated. The optimum method of sample storage using a preservative was investigated and implemented. Patients were recruited at any stage or grade of disease including those not on any treatment (watch and wait), those on treatment and/or post autologous stem cell transplants with maintenance chemotherapy. Patients were identified by LG-BCD type, treatment, and current status (stable, relapsed, partial or complete remission and minimal residual disease). The study presented in this thesis found that irrespective of LG-BCD type both naive and memory cells were detectable at increased levels in patients with relapse and that during infection cytotoxic T cells were raised, regardless of chemotherapy treatment. These cells could be used to discern between infection and relapse which would therefore influence the management of the patient. A population of naive cells (IFNy+) were found to function as memory cells which could have the potential to influence neoplastic B cells to proliferate and differentiate increasing the possibility of disease progression and relapse. Natural killer cells were also identified as present during infection though this could not be confirmed upon further investigation. Further study of a larger number of LG-BCD patients is crucial for confirming the involvement of these T cells which may be used to influence the management of treatment to improve patient's quality of life and prevent hospitalisation due to infection or relapse. Keywords: Thalidomide, lenalidomide, rituximab, chemotherapy, low grade B-cell disorder, flow cytometry, immunophenotyping, infection, relapse.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available