Researchers at the Smilow Cancer Center at Yale New Haven in New Haven, Connecticut, assessed a high-dose methotrexate (HDMTX) management guideline established at their institution in 2017 and determined the guideline enabled a safe and standardized method for reducing length of hospital stay with this treatment. Findings were reported in the Journal of Hematology Oncology Pharmacy.

The use of high-dose methotrexate, which includes doses of ≥1000 mg/m2, requires monitoring and management in order to reduce treatment complications, such as nephrotoxicity, the researchers explained in their report. The guideline implemented at their institution in 2017 included several components, such as changes to urinary alkalization protocols, once-daily monitoring of serum methotrexate, and possible early discharge with oral leucovorin if serum methotrexate was <1×10-7 to 3×10-7 moles/L.

The study was a retrospective chart review that included baseline data from February 2012 through September 2015 for patients receiving high-dose methotrexate. These data were compared with data collected from January 2017 through February 2018, which was a period after implementation of the guideline.

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The baseline cohort included 55 patients (cohort A), and 48 patients were evaluated from the period following guideline implementation (cohort B). Patients in cohort A showed a higher mean methotrexate dose, at 3558 mg/m2, compared with 2802 mg/m2 in cohort B.

In this analysis, cohort B showed a significantly lower mean length of hospital stay (3.89 days) than did cohort A (6.16 days; P =.003651). Patients had a mean methotrexate level at discharge of 7.7×10-8 moles/L in cohort A and 1.2×10-7 moles/L in cohort B. The average time to urine alkalization was similar between groups, at 7.63 hours for cohort A and 6.77 hours for cohort B. Nephrotoxicity was reported in 1.82% of patients in cohort A and in 6.25% of patients in cohort B (P =.249757).

“The results of this study demonstrate that the implementation of an institutional high-dose methotrexate guideline is safe and can successfully reduce the length of admission for patients receiving high-dose methotrexate,” the researchers concluded in their report.


Kowalski A, Jaszczur SM, Nadeau-Nguyen M, Merl MY. Assessment of high-dose methotrexate management guideline in adults with cancer at an academic medical center. J Hematol Oncol Pharm. 2021;11(2):69-73.