How I treat infant acute lymphoblastic leukemia

Infant acute lymphoblastic leukemia (ALL) is an aggressive malignancy that has historically been associated with a very poor prognosis. Despite large cooperative international trials and incremental increases in intensity of therapy, there has been no significant improvement in outcome over the last 3 decades. Using representative cases, we highlight the key differences between KMT2A-rearranged and KMT2A–germ line infant ALL, and how advances in molecular diagnostics are unpicking KMT2A–germ line genetics and guiding treatment reduction. We focus on KM2TA-rearranged infant B-cell ALL for which the last few years have seen the emergence of novel therapies that both are more effective and less toxic than conventional chemotherapy. Of these, there is promising early data on the efficacy and tolerability of the bispecific T-cell engager monoclonal antibody, blinatumomab, as well as the use of autologous and allogeneic chimeric antigen receptor T-cell therapy. We discuss how we can improve risk stratification and incorporate these new agents to replace the most toxic elements of currently deployed intensive chemotherapy schedules with their associated unacceptable toxicity.