KMT2A-rearranged acute lymphoblastic leukemia in infants: current progress and challenges

Chromosomal translocation of the KMT2A gene represents the cytogenetic hallmark of acute lymphoblastic leukemia diagnosed in infants (<1 year of age), driving a highly aggressive malignancy. For decades the event-free survival rates for these very young patients were at best ~40%. However, recent advances adding immunotherapy in the form of the bi-specific T-cell engager blinatumomab to the treatment led to encouraging results. In the present review we describe the current progress made, as well as the challenges that still lie ahead in terms of drug-related toxicity, the implementation of less toxic agents, acquired drug resistance, central nervous system involvement, and lineage switches. In addition, we touch on the benefit of preclinical models that can assist in guiding new treatment strategies.