Mutational Analysis as a Prognostic and Predictive Marker of Cardiovascular (CVD) Disease in Patients With Myelodysplasia

Not Applicable

• Conditions: Inflammation; Cardiovascular Diseases; MDS
• Interventions: Genetic: Genetic Mutations; Other: Inflammatory and lipid markers; Other: Computed Tomography (CT) of the heart

• Registration Number: NCT04110925
• Lead Sponsor: Sunnybrook Health Sciences Centre

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2019-08-23
• Status Verified: 2019-09
• Study Start: 2019-09
• Study First Submitted QC: 2019-09-30
• Last Update Submitted: 2019-09-30
• Study First Posted: 2019-10-01
• Last Update Posted: 2019-10-01
• Primary Completion: 2021-09
• Study Completion: 2021-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

• 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

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MDS patients	Computed Tomography (CT) of the heart	All Canadian MDS patients on the MDS-database to be included.
MDS patients	Genetic Mutations	All Canadian MDS patients on the MDS-database to be included.
MDS patients	Inflammatory and lipid markers	All Canadian MDS patients on the MDS-database to be included.

Primary Outcome Measures

Name	Time	Method
Measure the allelic frequency and type of myeloid cancer-associated mutations in MDS patients diagnostic bone marrow aspirates or slides	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	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	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

Secondary Outcome Measures

Name	Time	Method
Track how often newly discovered CAD from coronary CT leads to further intervention or changes in monitoring	2 years	The investigators will track any interventions in patients without a prior history of CAD who who are discovered to have occult CAD by coronary CT. This includes number of patients who were recommended: 1. medical management of CAD; 2. Referral to clinical cardiologist; 3. Invasive angiography
Screen for serum inflammatory cytokines in the blood of patients with incident or occult CAD	2 years	Measure TNFa, IL-1beta, IL-6 and an array of other inflammatory cytokines (to be determined) in the peripheral blood upon enrollment

Trial Locations

Locations (1)

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada