AUTHOR=Dai Chuanqiang , Zhang Youshu , Zhang Yao , Dong Yao TITLE=Case Report: Life-threatening cisplatin-induced myelosuppression in pediatric osteosarcoma: molecular mechanisms, pharmacogenomic profiling, and targeted clinical management JOURNAL=Frontiers in Pharmacology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1668180 DOI=10.3389/fphar.2025.1668180 ISSN=1663-9812 ABSTRACT=A 10-year-old female with osteoblastic osteosarcoma developed life-threatening cisplatin-induced myelosuppression (grade IV neutropenia/thrombocytopenia) following the eighth cycle of MAP chemotherapy. Critical pharmacological findings include a cumulative cisplatin dose of 720 mg/m2exceeding the pediatric safety threshold of 400 mg/m2. The CYP3A5*1/*1 genotype prolonged the half-life of cisplatin to 8.2 h. Cisplatin-specific biomarkers included serum magnesium 1.2 mg/dL and urinary N-acetyl-β-D-glucosaminidase 48 U/L. Targeted interventions (G-CSF, romiplostim, meropenem) led to hematological recovery within 14 days. This case implicates cisplatin overdose with impaired metabolic clearance as the primary toxicity mechanism.