Intrainfusion Drug Monitoring and Algorithm-Based Dose Adjustments for Children With ALL Receiving High-Dose...

Area of Science:

• Pediatric Oncology
• Pharmacokinetics
• Clinical Pharmacology

Background:

• High-dose methotrexate (HDMTX) at 5 g/m² is crucial for treating pediatric high-risk precursor B-cell acute lymphoblastic leukemia (ALL).
• Limited resources in low- and middle-income countries (LMICs) often prevent the administration of HDMTX due to intensive monitoring and toxicity support costs.

Purpose of the Study:

• To report the first experience of implementing an algorithm-based individualized HDMTX protocol in a public hospital in Costa Rica (HNN).
• To assess the feasibility and safety of providing HDMTX in an LMIC setting.

Main Methods:

• An algorithm-based protocol was developed to individualize HDMTX infusions by monitoring methotrexate levels at 2 and 6-8 hours.
• Infusion rates were adjusted downward based on predicted end-infusion concentrations to prevent toxicity.

Main Results:

• 196 infusions were administered to 52 pediatric patients between 2017 and 2019.
• Rate adjustments were needed in 24.6% of infusions.
• Significant toxicities (≥grade 3) were rare: 0.5% acute kidney injury, 1% neurotoxicity, 4.8% mucositis, and 24.6% neutropenia. No grade ≥4 toxicities occurred.

Conclusions:

• Real-time, algorithm-based individualized HDMTX infusion is a practical and safe method for LMICs.
• This approach enables the delivery of essential, high-dose chemotherapy in resource-limited environments.