New Agents

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Despite the improvements in survival, still a significant proportion of patients will die or suffer from deleterious side effects from current treatments. Therefore, new therapies are needed to overcome these limitations. Current developments in research and in diagnostic measures exponentially increased molecularly and functionally defined leukemia subgroups as well as treatment options in pediatric patients. These developments, which are to date mostly applied in heavily pretreated pediatric patients, demonstrated in some cases promising efficacy and safety profiles. Mechanisms that are in depth exploited include inhibition of various tyrosine kinases, epigenetic modification, cell cycle inhibition and enhancement of apoptotic processes via interference with BH-3 family of protein members. Early clinical trials in the pediatric population are currently being developed, ongoing, or finalized. Provided they fulfill the efficacy and safety requirements in larger pediatric patient populations in first and second-line trials, these drugs might be at the forefront to be incorporated into standard of care to prevent relapse and improve outcome. This chapter aims to provide an overview and a perspective over current preclinical rationales to apply targeted and untargeted non-immunotherapeutic compounds in leukemia treatment (immunotherapy is discussed elsewhere in this book), and provides an overview on clinical trials evaluating these drugs in the pediatric population.