Precision medicine in acute lymphoblastic leukemia.

Area of Science:

• Pediatric Oncology
• Hematology
• Molecular Therapeutics

Background:

• Childhood acute lymphoblastic leukemia (ALL) cure rates exceed 90% in clinical trials.
• Conventional chemotherapy dose intensity is nearing its limit.
• Improved outcomes require molecular, immuno-, and cellular therapies with risk stratification.

Purpose of the Study:

• To review current and emerging therapeutic strategies for childhood ALL.
• To highlight the role of molecular targets, risk stratification, and novel therapies.
• To discuss rational combinations of targeted therapies for improved outcomes.

Main Methods:

• Review of contemporary clinical trials and preclinical findings.
• Identification of genetic lesions and molecular targets in ALL subtypes.
• Analysis of efficacy for targeted agents, immunotherapies, and cellular therapies.

Main Results:

• ETV6-RUNX1 or hyperdiploid >50 ALL with MRD negativity can undergo treatment reduction.
• Philadelphia chromosome (Ph)-positive or Ph-like ALL with ABL-class fusion responds to dasatinib.
• High-risk ALL subtypes may respond to venetoclax; CAR-T cell therapy shows promise for B-ALL and T-ALL.

Conclusions:

• Precision medicine, including targeted therapies and immunotherapy, is crucial for advancing ALL treatment.
• Risk stratification identifies candidates for treatment de-escalation and escalation.
• Rational combination of therapies with non-overlapping toxicities is the future direction.