Predictive biomarkers for acute graft-versus-host-disease after allogeneic hematopoietic stem cell transplantation: a sixteen patient-donor couple in vitro study
Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesisAlternative title
Predikterande biomarkörer för akut transplantat-mot-värdsjukdom efter allogen hematopoietisk stamcellstransplantation: en in vitro studie med sexton patientdonatorpar (Swedish)
Allogeneic hematopoietic stem cell transplantation (HSCT) is a widely used medical procedure for treatment of various malignant and non-malignant diseases. However, there are still great risks associated with this treatment. A major complication of allogeneic HSCT is acute graft-versus-host disease (aGvHD). Due to difficulty in treating severe forms of acute GvHD it is desirable to identify predictive markers to assess the risk of patients developing aGvHD. Unfortunately, good biomarkers indicative of acute GvHD remain few. Therefore, the aim of this project is to shed further light on the topic by studying the graft in vitro in hope of finding correlations between expression or secretion of biomarkers and disease progression.
This study was conducted on sixteen patient-donor couples for allo-HSCT. Post HSCT, the patients were graded with no acute GvHD, grade I or grade II acute GvHD. We looked at markers for T lymphocytes using a mixed lymphocyte reaction (MLR) to analyze how graft cells responded to irradiated cells from the graft recipient. To this end, we used flow cytometry and Luminex to analyze the reactivity of the donor cells and the correlation of biomarkers with later in vivo development of grade 0 to II of acute GVHD. Ou main finding was a significant decrease (p=0.004) in the cell viability (7-AAD cells) of graft cells for patiens who later developed grade II acute GvHD, compared to patients with no acute GvHD. Overall there were indications of higher frquencies of donor effector T cells for grafts given to patiens who later developed grade II aGvHD. To better assess the correlation between dvelopment of higher stages of acute GvHD and the frequency of different biomarkers more in depth analysis and larger patient groups are needed.
Place, publisher, year, edition, pages
biomarkers, transplantation, leukemia, stem cell, in vitro
Engineering and Technology
IdentifiersURN: urn:nbn:se:kth:diva-173244OAI: oai:DiVA.org:kth-173244DiVA: diva2:852274