During recent decades, the prognosis of childhood acute lymphoblastic leukemia (ALL) has improved dramatically, nowadays, reaching a cure rate of almost 90%. These results are due to a better management and combination of old therapies, refined risk-group stratification and emergence of minimal residual disease (MRD) combined with treatment's intensification for high-risk subgroups. However, the subgroup of patients with refractory/relapsed ALL still presents a dismal prognosis indicating necessity for innovative therapeutic approaches. Areas covered: We performed an exhaustive review of current first-line therapies for childhood ALL in the worldwide main consortia, summarized the major advances for front-line and relapse treatment and highlighted recent and promising innovative therapies with an overview of the most promising ongoing clinical trials. Expert opinion: Two major avenues marked the beginning of 21st century. First, is the introduction of tyrosine-kinase inhibitor coupled to chemotherapy for treatment of Philadelphia positive ALL opening new treatment possibilities for the recently identified subgroup of Ph-like ALL. Second, is the breakthrough of immunotherapy, notably CAR T-cell and specific antibody-based therapy, with remarkable success observed in initial studies. This review gives an insight on current knowledge in these innovative therapeutic directions, summarizes currently ongoing clinical trials and addresses challenges these approaches are faced with.
Keywords: Acute lymphoblastic leukemia; Ph-like ALL; childhood; chimeric antigen receptor (CAR) T-cells; immunotherapy; risk stratification; tyrosine-kinase inhibitor.