Cohen, Oliver Charles;
(2024)
Prognostic Markers and Management Strategies in Systemic Amyloidosis.
Doctoral thesis (M.D(Res)), UCL (University College London).
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Abstract
BACKGROUND: Systemic amyloidosis is increasing in prevalence but remains a rare, potentially fatal disorder characterised by the misfolding of autologous proteins into an abnormal fibrillar form. Outcomes are dependent on amyloid subtype. AIMS: To improve diagnosis, management and understanding of prognosis of patients with amyloidosis. In terms of diagnosis, I will evaluate the diagnostic sensitivity of screening biopsies in AL and ATTR amyloidosis. I will also assess prognostic markers at baseline, and following treatment, in a large UK cohort of uniformly treated patients with a view to developing a new staging system for AL amyloidosis incorporating novel prognostic markers. I will focus on functional markers of prognosis such as longitudinal strain on echocardiogram and the 6-minute walk test. I shall also explore treatment outcomes with novel therapies (ixazomib-lenalidomidedexamethasone and daratumumab) in AL amyloidosis and the impact of chemotherapy on quality of life in patients with AL amyloidosis at a variety of timepoints. Finally, I will assess the value and outcomes of organ transplantation in patients with AL amyloidosis and apolipoprotein A-I amyloidosis. RESULTS AND CONCLUSION: Screening biopsies are valuable, particularly in AL amyloidosis, to avoid higher-risk target organ biopsies. Longitudinal strain, measured via echocardiogram, is prognostic at baseline and following chemotherapy in AL amyloidosis. It is independent of Mayo criteria and can be incorporated into a new prognostic staging system alongside cardiac biomarkers both at baseline and in evaluating response to treatment. The 6-minute walk test distance is also prognostic at baseline, whilst improvement in walk test at 12 months predicts survival. Health-related quality of life improves in patients achieving a complete haematological response or cardiac organ response and is an important marker in the holistic characterisation of treatment response. Ixazomib-lenalidomide-dexamethasone and Daratumumab monotherapy are both effective treatment options in AL amyloidosis. Renal transplantation is associated with very encouraging outcomes in carefully selected patients with AL amyloidosis. In Apolipoprotein A-I amyloidosis, renal, hepatic and cardiac transplantations all have a role and are associated with good long term outcomes.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | M.D(Res) |
| Title: | Prognostic Markers and Management Strategies in Systemic Amyloidosis |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10189810 |
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