The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
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Due to copyright reasons, an electronic copy of the thesis must be ordered from the faculty. In order for the faculty to have time to process the order, it must be received by the faculty no later than 2 days prior to the public defence. Orders received later than 2 days before the defence will not be processed. Inquiries regarding the thesis after the public defence must be addressed to the candidate.
Digital Trial Lecture – time and place
Adjudication committee
- First opponent: Associate Professor C. Heleen van Ommen, Sophia Children's Hospital Erasmus MC, The Netherlands
- Second opponent: Professor John-Bjarne Hansen, UiT- The Arctic University of Norway
- Third member and chair of the evaluation committee: Professor II Pål Andre Holme, University of Oslo
Chair of the Defence
Professor II Henrik Holmstrøm, Faculty of Medicine, University of Oslo
Principal Supervisor
Professor II Ellen Ruud, Faculty of Medicine, University of Oslo
Summary
Thromboembolism (TE) is an important toxicity of acute lymphoblastic leukemia (ALL) treatment, affecting about 5-7% of patients. However, the role of genetic risk factors is unclear. The aim of this thesis was to investigate whether common genetic variation, known to affect risk of TE in the general population, was associated with TE in patients with ALL. Secondly, to investigate the prevalence of asymptomatic central venous line (CVL)-related TE in children with ALL.
We collected constitutional DNA and prospectively registered TE in children and adults with ALL included in the Nordic Society of Pediatric Hematology and Oncology ALL2008 study from 2008 to 2016. We analyzed candidate genetic variants known to be associated with TE in the general adult population, and we investigated the common genetic etiology between TE in the general population and TE in patients with ALL. The prevalence of asymptomatic CVL-related TE was investigated in a single center prospective study using repeated ultrasonography examinations, and in a retrospective review of end-of-treatment echocardiography reports.
Two genetic variants, F11 rs2036914 and FGG rs2066865, were associated with TE in patients with ALL, with strongest association in adolescents. We confirmed that risk of TE increases with age, and we also found common genetic etiology between TE in the general adult population and TE in adolescents with ALL, but not children and adults, indicating that genetic risk of TE in ALL is also age dependent. This is an important basis for future thromboprophylaxis studies in patients with ALL.
We found that asymptomatic CVL-related TE is common during ALL treatment, but not associated with symptomatic TE, indicating that they are of little clinical importance and that screening is not warranted. We also found that right atrial thrombosis after end of ALL treatment was rare, and can be safely observed without treatment in the absence of risk factors.
Additional information
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