New insights into the antileukaemic immune response after stem cell transplantation
Stem cell transplantation from a foreign or family donor is a vital form of treatment, especially for patients with leukaemia. Approximately 3,000 transplants are carried out in Germany every year.. In a project supported by the German Research Foundation (DFG) over several years, the research group of Prof. Dr. med. Universitätsklinik für Hämatologie und Onkologie Magdeburg, together with researchers from Erlangen, Regensburg and Würzburg show that DNA damage in the T lymphocytes is associated with higher relapse rates of the underlying disease, especially in the first six weeks after transplantation. Their modulation could prevent disease relapses in the future. The work has been published in the renowned journal of the American Society of Haematology "Blood Journal".
At Magdeburg University Hospital, a special inpatient unit is available for stem cell transplantation in the University Department of Haematology and Oncology, which bears the internationally recognised JACIE (Joint Accreditation Committee International Society for Cellular Therapy and the European Group for Blood and Marrow Transplantation) seal of quality. In such a transplant, the patient's blood cells are first killed by chemotherapy and/or radiation and then replaced by the healthy donor stem cells.
Portrait Prof. Dr. med. Dimitrios Mougiakakos, Director of the University Clinic for Haematology and Oncology Magdeburg. Photographer: Sarah Kossmann/UMMD
Prof. Mougiakakos emphasises that the principle of action here is primarily immunological: "Donor immune cells, especially T lymphocytes, recognise retained leukaemia cells and destroy them. We call this process the 'Graft versus Leukemia (GvL)' effect and it is supposed to prevent the relapse of the disease. The better the T lymphocytes function, the stronger the GvL effect." For this reason, Prof. Mougiakakos says it is important to decipher the mechanisms that prevent T lymphocytes from functioning adequately after stem cell transplantation.
The research group was able to show that damage in the DNA of T lymphocytes in the first six weeks after transplantation is associated with functional deficits, an increased risk of relapse and a poorer overall survival rate. „In extensive cell and molecular biological investigations, we have been able to work out well that oxidative stress is responsible for this damage. The damaged T lymphocytes appear 'pre-aged' and are no longer able to fight leukaemia cells effectively," explains the oncologist. The team is now working on improving the DNA repair of T lymphocytes and thus their effectiveness in the fight against leukaemia, with the aim of translating these results into a clinical application.
Prof. Dr. med. Dimitrios Mougiakakos, Director of the University Clinic for Haematology and Oncology Magdeburg,