Discussion

We describe the clinical safety of HD-MTX in a cohort of children and adolescents with NHL treated with routine clinical care at a large tertiary center. We found that about a quarter of HD-MTX doses resulted in delayed clearance, though overall more than half of all patients experienced this during treatment. Similarly, about a quarter of all doses were associated with methotrexate-related serum creatinine elevations, again impacting more than half of all patients. Although 18% of doses were complicated by grade ≥3 mucositis, this impacted nearly 40% of patients in our cohort. Importantly, creatinine elevations and delayed clearance were independently associated with subsequent grade ≥3 mucositis, signifying the importance of early recognition and intervention in patients receiving HD-MTX. Our data are limited by the retrospective, single-center study design and relatively small sample size. In our practice, we can rapidly respond to methotrexate levels and serum creatinine elevations by adjusting intravenous fluids and/or modifying leucovorin rescue, potentially preventing therapeutic morbidity and mortality, though this takes considerable resources (staffing, laboratory capability, and clinical expertise). We strongly advocate for expanded access to methotrexate therapeutic monitoring globally, such that children in limited resource settings, who are most prominently impacted by NHL are given equitable access to this essential modality.