Dose-Capping Glucarpidase in Pediatric Patients for the Management of Delayed Clearance of High-Dose Methotrexate.

Authors

Christopher Phillips, Colleen Koehler, Gianna Galioto

Published in

Pediatric blood & cancer. Pages e70737. Oct 09, 2026. Epub Oct 09, 2026.

Abstract

High-dose methotrexate (HDMTX) can lead to toxicities including nephrotoxicity, myelosuppression, and mucositis. Glucarpidase is a recombinant bacterial enzyme that inactivates extracellular methotrexate (MTX). Prior studies suggest that glucarpidase doses <50 units/kg may effectively decrease serum MTX concentrations. The purpose of this study was to evaluate dose-capping glucarpidase at 1000 units in pediatric and young adults patients.
This retrospective, single-center study (2013-2024) included glucarpidase administrations of 1000 units after HDMTX administration (doses greater than 500 mg/m²). Glucarpidase doses ≥50 units/kg were excluded. The primary endpoint was the incidence of administrations achieving a clinically significant reduction (>95% reduction) in serum MTX concentrations following dose-capped glucarpidase, at first measurement by high-performance liquid chromatography (HPLC). MTX-related toxicities were reported.
Fourteen glucarpidase administrations were included. The median age was 14.3 years and the median glucarpidase dose was 19.2 units/kg. Twelve administrations (86%) had Grade 2-4 acute kidney injury (AKI) prior to glucarpidase. All 12 administrations with available HPLC data (100%) achieved a clinically significant reduction in serum MTX concentrations, with a median reduction of 99.5%. Among administrations with Grade 2-4 AKI, the median time to renal recovery was 6.9 days.
Glucarpidase doses capped at 1000 units (<50 units/kg) were associated with clinically significant reductions in serum MTX concentrations. Reduced-dose glucarpidase was generally well tolerated, with no unexpected safety concerns. While dose-capping may be considered in select patients, further prospective, dose-finding studies in humans are needed before employing this approach outside clinical trials.

PMID:
42851119
Bibliographic data and abstract were imported from PubMed on 09 Oct 2026.

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