8A. Developing new therapies for acute lymphoblastic leukaemia based upon molecular genetic abnormalities and immunotherapeutic targets

Focus of this project is to improve outcome of children with acute lymphoblastic leukemia (ALL) by the development of better targeted and personalized therapies. Many data are available from thousands of children with ALL from national and international studies regarding: (1) molecular genetic and epigenetic abnormalities, (2) therapy response measurements by minimal residual disease (MRD) monitoring and (3) toxicity reporting during therapy, (4) long-term outcome data on leukemia-free survival and on long-term side effects and quality of survival and on (5) administyered therapy components including chemotherapy, stem cell transplantation, antibody based immunotherapy and cellular therapy. In close collaboration with our trial and data center, our molecular diagnostic lab and our preclinical research groups on molecular genetics and immunotherapy we will study the clinical relevance of all these data and use these to develop more precise therapies for specific genetic and immunophenotypic risk groups of childhood ALL. chemotherapeutic developments and from therapeutic drug monitoring are studied and implemented in national and international clinical study protocols. Specific goals are:

– implementation of immunotherapies including antibody based strategies and cellular therapies in treatment protocols for frontline and relapsed ALL

– reduction of therapy and thereby improving quality of life for specific patient groups selected by genetic features and MRD

– improving cure rate by development of more effective and more specific therapies for molecular genetic and immunophenotypic subclasses of ALL

– more rational and specific use of chemotherapeutic agents