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Format:
Online
Author:
Adrianzen Herrera, Diego Andres
Dept./Program:
Center for Clinical and Translational Science
Year:
2023
Degree:
M.S.
Abstract:
Myelodysplastic syndromes (MDS) are a group of heterogeneous hematologic malignancies characterized by ineffective hematopoiesis and risk of progression to acute myeloid leukemia. MDS has been linked with immune dysregulation, as overly active immunity promotes inflammation and oncogenesis within the hematopoietic system. In recent years, autoimmunity has been defined as an important pathogenic pathway in patients with MDS and numerous studies have demonstrated high prevalence of autoimmune diseases among these patients. Despite this association, the clinical and prognostic implications of preexisting autoimmune disease for patients with MDS remains to be elucidated. An important gap in knowledge is defining the effect of preexisting autoimmunity on the survival of patients with MDS, as previous studies on small cohorts have reported contradictory results. I hypothesized that the prognostic effect of preexisting autoimmunity in MDS can be defined using a large, population-based, epidemiologically representative database of patients with MDS. In this thesis, I used the largest tumor registry in the United States (Surveillance, Epidemiology, and End Results) and Medicare administrative claim data to study how preexisting autoimmunity impacted the survival of patients with MDS. A retrospective, longitudinal, cohort study was conducted among MDS patients between 2007 and 2017, using Cox regression models to estimate the impact of autoimmunity on survival and competing-risk regression to estimate the impact on transformation to leukemia in the largest clinical study on the topic to date. I demonstrated that preexisting autoimmune disease before MDS diagnosis was associated with 11% decreased risk of death from any cause after accounting for clinical and MDS-specific confounders. In addition, I found that the effect of autoimmunity on leukemia transformation differs between MDS risk groups, with autoimmunity linked to higher leukemia transformation in low-risk MDS patients. These findings are clinically important and settle the previously conflicting results on this topic. They also constitute the basis for further research focusing on what are the molecular mechanisms behind our population findings.
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Access to this item embargoed until 03/25/2024.