Impact of Preexisting Autoimmune Disease on Myelodysplastic Syndromes Outcomes

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

Synchronous Bone Metastasis From Multiple Myeloma and Prostate Adenocarcinoma as Initial Presentation of Coexistent Malignancies

The radiographic appearance of bone metastases is usually determined by tumor histology and can be osteolytic, osteoblastic, or mixed. We present a patient with coexistent bone metastasis from multiple myeloma and prostate adenocarcinoma who exhibited synchronous bone involvement of both histologies within the same bone lesion, a rare phenomenon that has not been previously reported and led to atypical radiographic findings. The radiograph of a 71-year-old man with thigh swelling and pain demonstrated a lytic femoral lesion. Magnetic resonance imaging (MRI) confirmed a destructive process, but showed coexistent metaphyseal sclerosis. Multiple myeloma was suspected by demonstration of monoclonal gammopathy and confirmed by computed tomography (CT)-guided biopsy. Incidentally, CT demonstrated areas of sclerosis corresponding to T2 hypointensity on MRI. Further studies revealed osteoblastic spinal metastasis, prostate enhancement on CT and prostate-specific antigen (PSA) level of 90 ng/mL, concerning for concomitant prostate neoplasm. After endoprosthetic reconstruction, pathology of the femur identified both plasma cell neoplasm and metastatic prostate adenocarcinoma. An association between prostate cancer and multiple myeloma is hypothesized due to tumor microenvironment similarities and possible common genetic variations, however, coexisting bone metastases have never been reported. This unusual finding explains the discrepant imaging features in our patient and is evidenced that certain clinical situations merit contemplation of atypical presentations of common malignancies even if this leads to additional testing