Mutational Analysis as a Prognostic and Predictive Marker of Cardiovascular Disease in Patients With Myelodysplasia
试验速览
- 阶段
- 不适用
- 入组人数
- 400
- 试验地点
- 2
- 主要终点
- Measure the allelic frequency and type of myeloid cancer-associated mutations in MDS patients diagnostic bone marrow aspirates or slides
研究概览
简要总结
This study evaluates the relationship between myelodysplastic syndromes (MDS) and cardiovascular disease. MDS patients will be evaluated for the presence of mutations and whether they are associated with an increased risk of heart disease (CVD) and inflammation compared to healthy adults. Patients without symptoms of CVD will receive CT scans to assess for hidden disease and if that is related to their mutations.
详细描述
Myelodysplastic syndromes (MDS) are a type of blood cancer that can cause infection or bleeding because they prevent the formation of blood components and may lead to leukemia and death. MDS can arise from changes (or mutations) to a patient's DNA. MDS patients have increased risk of heart disease compared to healthy adults. The investigators will look for links between mutations in MDS patients and increased risk of heart disease. They will also use "CT imaging" to see if MDS patients have asymptomatic artery disease but may lead to heart disease in the future and if that is related to their mutations. The researcher will try to link mutations in MDS patients to markers of inflammation and to the amount of artery disease on CT imaging to look for patterns. The goal is to find certain mutations that are associated with inflammation and heart disease. This may ultimately allow hematologists to test MDS patients with these mutations for heart disease and/or treat them early so they have a better and longer life.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Screening
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of: myelodysplastic syndrome (MDS), myeloproliferative neoplasm (MPN), Chronic myelomonocytic leukemia leukemia (CMML), or low-blast acute myeloid leukemia (AML, blasts 20-29%) less than 24 months ago
- •Alive and registered in the MDS-Canada (MDS-CAN) database
- •Known comorbidity history and known history of cardiovascular disease
- •Able to provide peripheral blood sample for cytokine analysis
- •Able top provide samples for next generation sequencing (NGS) - if diagnosis 0-6 months ago: peripheral blood; if diagnosis 6-24 months ago: diagnostic bone marrow aspirate slides or peripheral blood
排除标准
- •MDS/MPN patients other than CMML due to higher prevalence of Janus Kinase 2 (JAK2) mutation (a known risk factor for CVD)
- •Disease progression without available diagnostic bone marrow slides for NGS
研究组 & 干预措施
MDS patients
All Canadian MDS patients on the MDS-database to be included.
干预措施: Genetic Mutations (Genetic)
MDS patients
All Canadian MDS patients on the MDS-database to be included.
干预措施: Inflammatory and lipid markers (Other)
MDS patients
All Canadian MDS patients on the MDS-database to be included.
干预措施: Computed Tomography (CT) of the heart (Other)
结局指标
主要结局
Measure the allelic frequency and type of myeloid cancer-associated mutations in MDS patients diagnostic bone marrow aspirates or slides
时间窗: 2 years
Screen for Presence of myeloid-cancer associated mutations and their variant allele frequencies (VAF) at diagnosis of MDS as measured through next generation sequencing of 40 myeloid genes.
Identify any correlation between selected myeloid mutations and/or their VAF with the presence of pre-existing incident or occult CAD
时间窗: 2 years
Comparing the presence of myeloid-cancer associated mutations and their variant allele frequencies (VAF) at diagnosis of MDS as measured through next generation sequencing of 40 myeloid genes between patients with pre-existing/occult CAD and those without.
Screen for occult and potentially clinically significant CAD in MDS patients by means of coronary CT
时间窗: 2 years
Patients at Sunnybrook hospital with no pre-existing history of CAD who receive CT of the heart and found to harbour occult CAD by means of coronary calcium scoring: 1. zero calcium (No CAD) 2. 1-400: mild-moderate calcification 3. \>400: severe calcification
次要结局
- Track how often newly discovered CAD from coronary CT leads to further intervention or changes in monitoring(2 years)
- Screen for serum inflammatory cytokines in the blood of patients with incident or occult CAD(2 years)