Eight-year national multicenter experience on the use of glucarpidase as effective rescue therapy for delayed methotrexate elimination after high-dose methotrexate cycles administered in children with hemato-oncological diseases

Abstract

Background

High-dose methotrexate (HDMTX) for cancer treatment can be complicated by delayed methotrexate elimination (DME) and associated acute kidney injury (AKI). This study evaluated glucarpidase for the treatment of DME and HDMTX-AKI in pediatric hemato-oncology patients.

Methods

This multicenter, retrospective study reviewed the medical records of pediatric patients (1–18 years) with ALL or NHL who were given glucarpidase as rescue therapy for DME or HDMTX-AKI at 13 Italian AIEOP centers between January 1, 2015, and June 30, 2023. Patients also received uniform supportive therapy, per study protocols and guidelines, to prevent and treat AKI.

Results

Data were available for 42/44 patients given glucarpidase, following i.v. HDMTX as monotherapy (non-high risk ALL [non-HR ALL], n=24), or within combined intensive chemotherapy blocks (HR-ALL, n=13; NHL, n=5). Median time to glucarpidase infusion was 53 hours (range 32–72). Most patients required glucarpidase during the first cycle of HDMTX. Glucarpidase led to a rapid decrease in plasma MTX levels (median 72.53 %; range 12.62–94.57 %). Median time for complete elimination of MTX and its metabolites was 216 hours (range 120–672). Recovery of renal function (return of serum creatinine to ≤1.5 times baseline value) took a median 18 days (range 4–72). Of the 22/42 patients (52 %) re-challenged with HDMTX (at 40–100 % of recommended dose), none experienced DME and all completed per-protocol number of HDMTX cycles.

Conclusions

Our experience shows that glucarpidase is effective and well tolerated for the treatment of DME and HDMTX-AKI in pediatric patients with hemato-oncologic diseases.