Implementation Science Methodology for the Successful Introduction of High-Dose Methotrexate for the Treatment of...

Despite the excellent outcomes achieved for pediatric mature B-cell non-Hodgkin lymphoma (MB-NHL) in high-income countries, outcomes remain very poor in low- and middle-income countries. High-dose methotrexate (HD-MTX), which is highly efficacious for the disease, is still not commonly used in low-resource settings due to the potential for treatment-associated toxicity. Though there have been more recent reports of successful use of HD-MTX in resource-limited settings, there are no reports to date regarding the methodology used to safely introduce HD-MTX in these environments. Subsequently, at our treatment center in northern Tanzania, we endeavored to utilize implementation science methodology to elucidate generalizable methods to allow for a safe introduction of HD-MTX in a resource-limited setting.

The Active Implementation Frameworks were utilized as a starting point to generate an initial implementation plan. Intervention fit was assessed, and resource mapping and cost analysis were completed. Key stakeholders were identified and engaged. Novel educational strategies, decision support tools, and protocol fidelity monitoring systems were developed.

Following completion of all planning and education activities, use of a new HD-MTX containing MB-NHL protocol began in October of 2024. As of June 2025, 27 cycles of HD-MTX have been given to a cumulative total of 10 patients. Few protocol deviations have occurred, and only one Grade III non-hematologic adverse event has been reported.

The use of implementation science methodology allowed a careful introduction of the use of HD-MTX for the treatment of pediatric MB-NHL in a resource-limited setting.