Management of relapsed acute lymphoblastic leukemia in childhood with conventional and innovative approaches

To review and summarize the available evidence on factors predicting prognosis of children with relapsed acute lymphoblastic leukemia (ALL) and on the currently used treatment strategies, as well as on the most promising and innovative molecular or cellular therapies.

Relapse still represents the most common cause of treatment failure, occurring in approximately 15-20% of childhood ALL. Risk-oriented standard salvage regimens are mostly based on combinations of the same agents incorporated in frontline therapies. Allogeneic hematopoietic stem cell transplantation (HSCT) is largely employed as postremission therapy, being superior to chemotherapy in high-risk patients. With conventional therapies including HSCT, 40-50% of children with relapsed ALL can be rescued. Thus, innovative approaches are needed to further improve the outcome of patients, especially when carrying poor prognostic factors. The last decade has witnessed the development of novel agents, including nucleoside analogues, anti-CD22 monoclonal antibodies and bi-specific, anti-CD3/CD19 antibodies, together with new formulations of existing chemotherapeutic agents and targeted molecules, such as tyrosine kinase inhibitors and FLT3 inhibitors.

A significant proportion of children with relapsed ALL are salvaged by risk-oriented therapies. Novel agents should be integrated into combination regimens with the aim of further improving outcome of patients.