Therapeutic drug monitoring in the treatment of childhood acute lymphoblastic leukemia – A practical guideline

Treatment regimens for childhood acute lymphoblastic leukemia have developed steadily over the last decades, significantly improving patient outcomes.This has been achieved mainly by intensifying therapy, which also increased the risk of associated toxicity.To address this issue, therapeutic drug monitoring (TDM) has been introduced in clinical research and, for certain chemotherapeutic agents, as standard of care in protocols like the ALLTogether1.The goal of TDM is to optimize delivery of a given cytotoxic drug, while minimizing the risk of toxicity.Notwithstanding, only a subset of drugs included in the backbone of ALL treatment will be eligible for TDM, since specific pharmacokinetic and pharmacodynamic properties need to apply.Despite the recent rise of innovative therapies like immunotherapy, cytotoxic drugs remain a core component of ALL treatment, making the application of TDM crucial for improving patient outcomes.Among these chemotherapeutic agents, we focus on the monitoring of asparaginase, high-dose methotrexate, 6-mercaptopurine and low dose methotrexate in maintenance therapy, tyrosine kinase inhibitors and busulfan, in order to enhance clinical effectiveness.This narrative review further explains how TDM for these drugs should be conducted and offers practical recommendations for managing them in childhood ALL treatment.Moreover, ongoing research in TDM will allow for more personalized therapy delivery in frontline strategies, while optimizing care with lesser toxicity burden for patients.