Pharmacogenomics of treatment toxicities in pediatric B-Cell ALL: toward safer precision therapy

Review of treatment-induced toxicity mechanisms in ALL (thiopurines, fluoropyrimidines, asparaginase, steroids) and CPIC levels A/B actionable pharmacogenomic variants (TPMT, NUDT15, DPYD, CYP3A5)

This review synthesizes pharmacogenomic mechanisms of major treatment-induced toxicities in pediatric B-ALL: myelosuppression by thiopurines (TPMT, NUDT15), fluoropyrimidine toxicity (DPYD), metabolic variability of steroids and vincristine (CYP3A5, CYP3A4). It positions pharmacogenomics as a toxicity-reduction tool in the current context of treatment de-escalation for low-risk ALL, and proposes an integrated multi-gene preemptive testing framework in pediatric oncology.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The treatment de-escalation context in low-risk pediatric ALL makes pharmacogenomics particularly relevant: avoidable toxicities can limit dose reduction. This review provides a practical framework for pediatric oncology teams wishing to integrate a preemptive TPMT/NUDT15/DPYD PGx panel into their ALL treatment protocols.

Clinical impact: 3/3 · Evidence strength: 3/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 9/10