Stratification and Treatment of Infants

Acute lymphoblastic leukemia (ALL) in infants accounts for less than 5% of childhood ALL. Approximately 70–80% of the patients present with a very aggressive form of ALL with KMT2A gene rearrangement (KMT2A-r) and most of the published outcomes are dismal with <40% event-free survival rate even with intensive chemotherapy with or without hematopoietic stem cell transplantation. Refinement in risk stratification based on leukemia biology and minimal residual disease, as well as an introduction of emerging novel immunotherapies and molecular-targeted drugs to contemporary therapy through international collaboration would be a key solution for further improvement in outcome. In contrast, infants with germline KMT2A gene (KMT2A-g) present as less aggressive leukemia, and 70–90% of the patients are cured with conventional chemotherapy. However, recent genomics has uncovered genetic heterogeneity of KMT2A-g ALL in infants, which may lead to a better risk-stratified therapy in the future. Considering the vulnerability of infants, risks on both acute and late toxicities are of great issue, which should be taken into account for future therapy development.