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.