CAR T in Childhood Acute Lymphoblastic Leukemia

Chimeric antigen receptor (CAR) T-cell therapy directed against CD19 shows durable responses in children, adolescents and young adults (CAYA) with B-cell precursor acute lymphoblastic leukemia. The results of the multicenter international ELIANA trial, led to the FDA and EMA registration of tisagenlecleucel. The FDA approved CAR T cell therapy. Cellular therapy has been introduced internationally for CAYA with relapsed or refractory disease. CAR T cell therapy has a different toxicity profile compared to conventional strategies. Cytokine release syndrome and immune cell associated neurotoxicity syndrome are specific side effects caused by activation and expansion of the engineered effector cells. International collaboration has led to standardized toxicity management guidelines. This contributed to the effective implementation of CAR T cell therapy in pediatric oncology. The complete response rate to CAR T cell therapy is over 80%; nevertheless, relapses occur in approximately 50% of the patients due either antigen loss or loss of functional CAR T cells. In addition, numerous clinical trials have been initiated to improve currently available therapies. These novel strategies include targeting T-cell ALL.