New developments in ALL in AYA.

The outcome for adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) has improved, mostly based on the use of pediatric-inspired intensive protocols. Due to increasing disease resistance and treatment-related toxicity with age, further improvements are now expected from the expanding knowledge of ALL biology, more accurate risk stratification, and the early introduction of targeted small molecules and immunotherapy. In the last decade, the rate of AYA with B-cell precursor ALL with undetermined genetic drivers ("B-other") has shrunk from 40% to fewer than 10%. The high-risk subgroup of Philadelphia-like ALL is the most frequent entity diagnosed in this age range, offering a multitude of potentially actionable targets. The timely and accurate identification of these targets remains challenging, however. Early minimal residual disease (MRD) monitoring has become a standard of care for the risk stratification and identification of patients likely to benefit from an allogeneic hematopoietic stem cell transplantation. Recently approved immunotherapies are moving frontline to eradicate MRD, to improve the outcome of high-risk patients, and, eventually, to reduce treatment burden. Comprehensive care programs dedicated to AYA with cancer aim at improving inclusion in specific clinical trials and at giving access to appropriate psychosocial support, fertility preservation, and survivorship programs.