Arulogun, Suzanne O.; (2025) Analysis of clinical aspects of diagnosis, treatment outcomes and prognostication in Waldenstrom Macroglobulinaemia. Doctoral thesis (M.D(Res)), UCL (University College London).

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Abstract

Waldenström macroglobulinaemia accounts for approximately 1.9% of all non-Hodgkin lymphoma diagnoses. It is characterised by the presence of a serum monoclonal immunoglobulin M protein and the infiltration of the bone marrow with clonally derived lymphoplasmacytic cells. Compared with other non-Hodgkin lymphomas, it is relatively understudied. Through a series of retrospective subgroup-based statistical and descriptive analyses, this thesis aims to explore several clinical aspects of diagnosis, treatment outcomes and prognostication in Waldenström macroglobulinaemia. Chapter one contains a broad review of the currently available literature pertaining to the epidemiology, clinical presentation, diagnosis, treatment and complications of Waldenström macroglobulinaemia. An overview of the methodological approach to the research undertaken in this thesis is summarised in Chapter two. Any methodological considerations that are specific to the individual studies are included within the relevant chapter. Chapter three reports the largest series published to date of real-world experience of the therapeutic combination of bendamustine plus rituximab in the treatment of Waldenström macroglobulinaemia. It details patient outcomes in terms of depth of response, and overall and progression-free survival outcomes of patients following treatment with bendamustine plus rituximab in the frontline and relapsed settings. The study carefully delineates the impact of bendamustine dosing and other independent variables on outcome, and reports on surrogate markers of toxicity of treatment. In Chapter four, the 20-year experience of the treatment of Waldenström macroglobulinaemia with autologous stem cell transplantation in a specialist centre is described, with an analysis of response and survival outcomes. Chapter five comprises two projects in Bing Neel syndrome: an analysis of the long-term survival outcomes of a relatively large series of patients treated with methotrexate-based regimens in the frontline setting, and a description of the radiological features of Bing Neel syndrome before and after treatment using highly specialised combined metabolic- and magnetic resonance imaging-based techniques. Chapter six contains a clinicoradiopathological analysis of a series of patients with focal bone marrow lesions, a previously undescribed manifestation and complication of Waldenström macroglobulinaemia. The thesis concludes with a discussion the impact of the reported studies on the clinical management of Waldenström macroglobulinaemia, as well as the author’s perspective on some future directions. The impact and implications of the individual projects are also highlighted in the Discussion sections of the relevant research chapters. During the period of candidature, most of the original research work presented in this thesis has undergone a peer review process prior to acceptance for publication or presentation at international conferences, as listed in the UCL research paper declaration and detailed in the Author contribution statement.

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