Thesis defense Linde Dekker

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Immunotherapy has significantly improved overall survival of pediatric patients with acute leukemia. Nevertheless, procedure-related life-threatening complications, together with relapsed disease, hamper the life-saving effect of immunotherapy and highlight the need for improvement. The goal of this thesis was to investigate potential enhancements for two currently applied immunotherapies in clinical care, thereby aiming to improve clinical outcome in pediatric patients with acute leukemia. These two therapies include allogeneic hematopoietic cell transplantation and chimeric antigen receptor T cell therapy. This thesis shows that immunosuppressive therapies influence the recovery of the immune system and that individualized dosing strategies can be crucial for improving clinical outcome. Furthermore, the identification of risk factors for therapy failure or for the onset of life-threatening complications are essential for the development and implementation of preventative measures and adjusted or alternative treatment options. The data presented in this thesis thereby contribute to further optimization of cellular therapies to eventually improve clinical outcome of pediatric patients with acute leukemia.