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| Name | Class |
|---|---|
| Ontario Molecular Pathology Research Network | UNKNOWN |
| Queen's University | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MDS patients | Other | All Canadian MDS patients on the MDS-database to be included. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Genetic Mutations | Genetic | DNA sequencing for mutations to be obtained by bloodwork within 6 months of diagnosis, or by accessing diagnostic bone marrow aspirate slides. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Measure the allelic frequency and type of myeloid cancer-associated mutations in MDS patients diagnostic bone marrow aspirates or slides | 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. | 2 years |
| Screen for occult and potentially clinically significant CAD in MDS patients by means of coronary CT | 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:
| 2 years |
| Identify any correlation between selected myeloid mutations and/or their VAF with the presence of pre-existing incident or occult CAD | 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. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Track how often newly discovered CAD from coronary CT leads to further intervention or changes in monitoring | 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:
|
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rena Buckstein, MD | Contact | 416-480-5847 | rena.buckstein@sunnybrook.ca |
| Name | Affiliation | Role |
|---|---|---|
| Rashmi S Goswani, MD | Sunnybrook Health Sciences Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sunnybrook Health Sciences Centre | Toronto | Ontario | M4N 3M5 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28277851 | Background | Stahl M, Zeidan AM. Management of lower-risk myelodysplastic syndromes without del5q: current approach and future trends. Expert Rev Hematol. 2017 Apr;10(4):345-364. doi: 10.1080/17474086.2017.1297704. Epub 2017 Mar 9. | |
| 29296849 | Background | Brunner AM, Blonquist TM, Hobbs GS, Amrein PC, Neuberg DS, Steensma DP, Abel GA, Fathi AT. Risk and timing of cardiovascular death among patients with myelodysplastic syndromes. Blood Adv. 2017 Oct 18;1(23):2032-2040. doi: 10.1182/bloodadvances.2017010165. eCollection 2017 Oct 24. |
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| Inflammatory and lipid markers | Other | Bloodwork to be done for lipid profile, c-reactive protein (CRP), and multiplex chemokine/cytokine analysis. |
|
| Computed Tomography (CT) of the heart | Other | Sunnybrook Patients with no history of cardiovascular disease [ex: past/present coronary artery disease (CAD), peripheral vascular disease (PVD), angina, myocardial infarction (MI), stroke, transient ischemic attack (TIA), or stents], not pregnant, and able to undergo CT will receive a CT of the heart to look for and quantify any occult coronary artery disease. |
|
| 2 years |
| Screen for serum inflammatory cytokines in the blood of patients with incident or occult CAD | Measure TNFa, IL-1beta, IL-6 and an array of other inflammatory cytokines (to be determined) in the peripheral blood upon enrollment | 2 years |
| 24030381 | Background | Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P, Yoon CJ, Ellis P, Wedge DC, Pellagatti A, Shlien A, Groves MJ, Forbes SA, Raine K, Hinton J, Mudie LJ, McLaren S, Hardy C, Latimer C, Della Porta MG, O'Meara S, Ambaglio I, Galli A, Butler AP, Walldin G, Teague JW, Quek L, Sternberg A, Gambacorti-Passerini C, Cross NC, Green AR, Boultwood J, Vyas P, Hellstrom-Lindberg E, Bowen D, Cazzola M, Stratton MR, Campbell PJ; Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013 Nov 21;122(22):3616-27; quiz 3699. doi: 10.1182/blood-2013-08-518886. Epub 2013 Sep 12. |
| 30182347 | Background | Elbaek MV, Sorensen AL, Hasselbalch HC. Cardiovascular disease in chronic myelomonocytic leukemia: do monocytosis and chronic inflammation predispose to accelerated atherosclerosis? Ann Hematol. 2019 Jan;98(1):101-109. doi: 10.1007/s00277-018-3489-0. Epub 2018 Sep 4. |
| 28636844 | Background | Jaiswal S, Natarajan P, Silver AJ, Gibson CJ, Bick AG, Shvartz E, McConkey M, Gupta N, Gabriel S, Ardissino D, Baber U, Mehran R, Fuster V, Danesh J, Frossard P, Saleheen D, Melander O, Sukhova GK, Neuberg D, Libby P, Kathiresan S, Ebert BL. Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease. N Engl J Med. 2017 Jul 13;377(2):111-121. doi: 10.1056/NEJMoa1701719. Epub 2017 Jun 21. |
| 21527159 | Background | Okwuosa TM, Greenland P, Ning H, Liu K, Bild DE, Burke GL, Eng J, Lloyd-Jones DM. Distribution of coronary artery calcium scores by Framingham 10-year risk strata in the MESA (Multi-Ethnic Study of Atherosclerosis) potential implications for coronary risk assessment. J Am Coll Cardiol. 2011 May 3;57(18):1838-45. doi: 10.1016/j.jacc.2010.11.053. |
| ID | Term |
|---|---|
| D002318 | Cardiovascular Diseases |
| D007249 | Inflammation |
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D009154 | Mutation |
| ID | Term |
|---|---|
| D014644 | Genetic Variation |
| D055614 | Genetic Phenomena |
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