Dose adjustment strategy for high-dose methotrexate-induced toxicities in pediatric acute lymphoblastic leukemia: based on population PK analysis and exposure-toxicity relationship.

• Tác giả: Ailing Cao, Jianpei Fang, Yanping Guan, Min Huang, Xinyu Li, Shu Liu, Kunyin Qiu, Jian Wang, Xueding Wang, Lvhong Xu, Qiaolan Xuan, Yating Zhang, Dunhua Zhou, Zhong Zuo
• Ngôn ngữ: eng
• Ký hiệu phân loại: 302.545 Isolation
• Thông tin xuất bản: Germany : Cancer chemotherapy and pharmacology , 2025
• Bộ sưu tập: NCBI
• ID: 113138

Tóm tắt

PURPOSE: High-dose methotrexate (HD-MTX) is the cornerstone of the therapy for acute lymphoblastic leukemia (ALL). However, severe adverse events are frequently reported despite standard supportive cares. Therefore, we aim to develop a new strategy to individualize HD-MTX and improve patient safety. METHODS: A retrospective study was conducted in which toxicity were evaluated in 134 patients with 461 HD-MTX treatment courses. All of the patients experienced standard supportive cares. Exposure-toxicity analysis was conducted to obtain the target concentration and area under the curve (AUC) of MTX. Population PK model was established for dose simulations. RESULTS: A high rate of severe toxicities (78.1%) was observed. Patients with C CONCLUSION: MTX C