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Intrainfusion Drug Monitoring and Algorithm-Based Dose Adjustments for Children With ALL Receiving High-Dose
Karol Acevedo1, Gabriela Soto1, Mary C Shapiro2,3
1Hematology Department, Hospital Nacional de Niños, Dr Carlos Sáenz Herrera, Caja Costarricense de Seguro Social, San José, Costa Rica.
Insights
High-dose methotrexate (HDMTX) infusions for pediatric precursor B-cell ALL are now safely administered in low-resource settings. An algorithm-based protocol individualizes HDMTX, preventing toxicity and improving patient outcomes.
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.
Purpose:
Infusions of high-dose methotrexate at 5 g/m2 over 24 (HDMTX) as a single infusion for pediatric patients with high-risk precursor B-cell ALL are known to lead to superior outcomes. The Hospital Nacional de Niños Dr Carlos Sáenz Herrera, part of the public system Caja Costarricense de Seguro Social in Costa Rica (HNN), has been historically unable to provide this therapy secondary to the required intensive monitoring and cost-prohibitive toxicity support.
Methods:
We report our experience providing HDMTX at HNN, to our knowledge, for the first time using an algorithm-based individualized HDMTX protocol designed to prevent toxic levels of methotrexate. The protocol checks intrainfusion methotrexate levels at hours 2 and 6 or 8, with adjustments in the infusion downward if levels predict a high/toxic end infusion concentration.
Results:
Fifty-two patients (who received 196 total evaluable infusions between 2017 and 2019) were included. Rate adjustments were required during 51 infusions (24.6%). Significant methotrexate-related toxicities were rare and included acute kidney injury (≥grade 3, 0.5%, n = 1), neurotoxicity (≥grade 3, 1%, n = 2), mucositis (≥grade 3, 4.8%, n = 10), and neutropenia (≥grade 3, 24.6%, n = 51). No ≥grade 4 toxicities occurred.
Conclusion:
A real-time, algorithm-based individualized HDMTX infusion is a practical and safe way to administer HDMTX in a low- and middle-income country.
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