Projectdetails

of


Clonal hematopoiesis and cardiovascular disease after autologous hematopoietic cell transplantation

Keywords:
cardiovascular hematopoiesis mutations

Researchers:
prof.dr. E. Vellenga
dr. G.A. Huls
I.A. van Zeventer

Nature of the research:
Translational research focusing on clonal hematopoiesis in autologous hematopoietic cell transplantation. This subproject involves collecting and analyzing patient data in a retrospective setting.

Fields of study:
haematology genetics cardiology

Background / introduction
Autologous hematopoietic cell transplantation (AHCT) is a widely used treatment option for patients with lymphoma and multiple myeloma. Late effects after AHCT contribute to significant morbidity and mortality and include cardiovascular events as well as metabolic disturbances (dyslipidemia, diabetes) (1,2). There is now increasing evidence that clonal hematopoiesis, defined as the presence of somatic mutations in peripheral blood, is detected in healthy individuals upon ageing (3). Interestingly, clonal hematopoiesis inferred an increased risk for cardiovascular disease in ageing individuals (4). We hypothesize that clonal hematopoiesis may explain the accelerated cardiovascular ageing phenotype in long-term AHCT survivors.
Research question / problem definition
We therefore aim to study the relation between clonal hematopoiesis and cardiovascular morbidity and mortality after AHCT. This project will focus on describing the incidence of cardiovascular events in patients who survive >2 years after AHCT, together with known cardiovascular risk factors (dyslipidemia, diabetes and hypertension). Occurrence of events will be related to AHCT-specific characteristics. Ultimately, we aim to use targeted next-generation sequencing techniques to determine the presence of clonal hematopoiesis and relate this to cardiovascular outcome.
Workplan
A comprehensive database of consecutive AHCT patients with basic clinical variables is already available. The student will contribute to collection of data regarding cardiovascular events and traditional risk factors. Data will be gathered from electronic patient records and by contacting (shared care) hospitals or general practitioners. For data analysis, various statistical techniques will be used.

This subproject is part of an ongoing project. The student will learn how to perform a retrospective clinical research project and various statistical techniques. Participation in the analyses of subsequent next-generation sequencing experiments is optional.
References
1. Cupit-Link MC et al (2018). Relationship between Aging and Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant, 2(5), e000250.
2. Armenian SH et al (2017). National Institutes of Health Hematopoietic Cell Transplantation Late Effects Initiative: The Cardiovascular Disease and Associated Risk Factors Working Group Report. Biol Blood Marrow Transplant, 23, 201-210.
3. Jaiswal, S et al (2014). Age-related clonal hematopoiesis associated with adverse outcomes. New England Journal of Medicine, 371(26), 2488-2498.
4. Jaiswal, S et al (2017). Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease. New England Journal of Medicine, 377(2), 111-121.
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Laatst gewijzigd: 23 februari 2012