Therapies on the horizon for childhood acute lymphoblastic leukemia

The prognosis for children with the most common childhood malignancy, acute lymphoblastic leukemia (ALL), has improved dramatically. However, the burden of therapy can be substantial, with long-term side-effects, and certain subgroups continue to have a poor outcome.

The recent discovery of new genetic alterations in high-risk subsets provides targets for precision medicine-based interventions using existing Food and Drug Administration approved agents. Novel immunotherapeutic approaches are being deployed in relapsed ALL, one of the leading causes of cancer cell death in children. Moreover, genomic analysis has charted the evolution of tumor subclones, and relapse-specific alterations now provide a mechanistic explanation for drug resistance, setting the stage for targeted therapy. There is greater recognition that host factors - genetic polymorphisms - influence cancer risk, response to therapy, and toxicity. In the future, it is anticipated that they will be integrated into clinical decision making to maximize cure and minimize side-effects. Recent efforts to limit prophylactic central nervous system irradiation have been successful, thereby sparing many children late neurocognitive impairments.

Integration of advances in precision medicine approaches and novel agents will continue to increase the cure rate and decrease the burden of therapy for childhood ALL.