The potential of precision medicine for childhood acute lymphoblastic leukemia: opportunities and challenges

ABSTRACT

Introduction: Although overall survival rates for children with acute lymphoblastic leukemia (ALL) are excellent, the prognosis for certain patients remains suboptimal. Risk-stratification has improved outcomes but 50% of relapses occur in children defined as ‘good risk’ at diagnosis. Precision medicine has the potential to employ novel treatments that will replace more toxic conventional therapy as well as improve outcomes, especially in cancers where response rates remain poor.

Areas covered: A literature search was performed on PubMed using the keywords below. This review describes the history of pediatric ALL treatment from broad risk-based strategies to recent discoveries of targetable lesions that define biological subgroups. This article also describes potentially targetable lesions and pathways associated with drug-resistant relapsed ALL and summarize early results of treatment studies. Finally, targeted immunotherapeutic approaches are discussed.

Expert commentary: The precision medicine approach shows promise for treatment of certain types of de novo and drug-resistant ALL. However, genomic heterogeneity requires each case to have an individualized approach. There are a number of novel agents in the pipeline for lesions previously considered ‘undruggable’ and further refinement and incorporation of targeted treatment into front-line therapy to prevent relapse is an important strategy to improve outcomes for pediatric ALL and will likely become standard of care.

KEYWORDS:

• Acute lymphoblastic leukemia
• precision medicine
• targeted therapy
• relapse
• drug resistance
• epigenetics
• immunotherapy

Declaration of interest

W Carroll has received grants from the National Cancer Institute of Health (R01 CA140729-05), The Leukemia and Lymphoma Society Specialized Center for Research and the Perlmutter Cancer Center (P30 CA016087). J Pierro reports receiving the St. Baldrick’s Foundation Fellowship Award and the Alex’s Lemonade Stand Young Investigator Grant. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.