Abstract
Waldenström’s Macroglobulinemia (WM) and IgM-related disorders are rare B-cell malignancies that have unique clinical features, pathophysiology and reactions to therapeutic agents. The research described in this thesis was conducted to gain insight into various disease manifestations of WM and IgM-related disorders, aiming to help improve diagnosis, therapy, and patient outcomes. Chapter 2 describes the efficacy of rituximab-fludarabin in the treatment of central nervous system involvement of WM (Bing Neel Syndrome). Chapter 3 contains a study on the clinicopathological aspects and outcomes of renal disease related to WM. This study revealed a large variance in renal pathology including the first description of Thrombotic Microangiopathy in this setting, and demonstrated a shorter overall survival for patients with WM related renal disease. Chapter 4 contains an international consensus guideline on the diagnosis and management of IgM related neuropathies. Chapter 5 comprises a study that identified the presence of the MYD88 L265P mutation in the majority of patients with IgM paraprotein related anti-MAG peripheral neuropathy, suggesting a biological link to WM. Finally, chapter 6 contains a study on the effect of a novel oral BTK inhibitor (ibrutinib), on serum chemokines, cytokines, hepcidin and iron metabolism, identifying the pretreatment level of the chemokine CXCL13 as a predictor for the response to ibrutinib.
Original language | English |
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Qualification | Doctor of Philosophy |
Awarding Institution |
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Supervisors/Advisors |
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Award date | 8 Feb 2019 |
Print ISBNs | 9789463612111 |
Publication status | Published - 2019 |