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Introduction <p>Methotrexate (MTX) is a pivotal therapeutic agent in the treatment of various cancers, including pediatric acute lymphoblastic leukemia (ALL). High-dose MTX (HD-MTX) therapy remains a key component of contemporary ALL treatment protocol. However, little is known about the effect of add-on therapy with acetazolamide (ACZ) on facilitating MTX clearance in pediatric patients with ALL.</p> Materials and methods <p>We retrospectively included cases of newly diagnosed pediatric high-risk ALL between December 2022 and July 2025 at Chang Gung Memorial Hospital. Medical records during the HD-MTX consolidation phase were reviewed, with a focus on instances where the first serum MTX level exceeded 1.0 µmol/L. Patients were categorized into ACZ-added and ACZ-free subgroups to evaluate the impact of ACZ on MTX clearance. Outcomes of interest included time to MTX normalization, incidence of delayed MTX clearance, 24-hour MTX decrement rate, and average daily urine output.</p> Results <p>A total of 29 patients were enrolled. Of these, 18 were allocated to the ACZ-free subgroup and 11 to the ACZ-added subgroup. Baseline characteristics, including age at enrollment, leukemic subtype, HD-MTX cycle at enrollment, and anthropometric parameters, were comparable between the subgroups. The ACZ-added subgroup demonstrated a significantly higher 24-hour MTX decrement rate (79.2% vs. 74.2%; <i>P</i> = 0.0129), lower incidence of delayed MTX clearance (63.6% vs. 100%; <i>P</i> = 0.0139), and faster time to MTX normalization (3.0 vs. 5.0 days; <i>P</i> = 0.0047).</p> Conclusions <p>Adjunctive ACZ may facilitate MTX clearance during HD-MTX therapy. The observed improvement in MTX clearance may be attributable to the urine alkalinization effect of ACZ, although the underlying mechanism was not directly investigated in this study. Adjunctive ACZ appears to be an effective and well-tolerated strategy for pediatric patients with ALL receiving HD-MTX. Nevertheless, larger prospective studies are warranted to validate these preliminary findings.</p>

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The introduction of acetazolamide lowers the risk of delayed methotrexate clearance in pediatric leukemia patients treated with high-dose methotrexate therapy

  • 期刊论文

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  • 发表日期：

    2026年8月3日

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  • Yi-Lun Wang,
  • Tsung-Yen Chang,
  • Shih-Hsiang Chen,
  • Yi-Wen Hsiao,
  • Yu-Chuan Wen,
  • Tang-Her Jaing

摘要

Introduction

Methotrexate (MTX) is a pivotal therapeutic agent in the treatment of various cancers, including pediatric acute lymphoblastic leukemia (ALL). High-dose MTX (HD-MTX) therapy remains a key component of contemporary ALL treatment protocol. However, little is known about the effect of add-on therapy with acetazolamide (ACZ) on facilitating MTX clearance in pediatric patients with ALL.

Materials and methods

We retrospectively included cases of newly diagnosed pediatric high-risk ALL between December 2022 and July 2025 at Chang Gung Memorial Hospital. Medical records during the HD-MTX consolidation phase were reviewed, with a focus on instances where the first serum MTX level exceeded 1.0 µmol/L. Patients were categorized into ACZ-added and ACZ-free subgroups to evaluate the impact of ACZ on MTX clearance. Outcomes of interest included time to MTX normalization, incidence of delayed MTX clearance, 24-hour MTX decrement rate, and average daily urine output.

Results

A total of 29 patients were enrolled. Of these, 18 were allocated to the ACZ-free subgroup and 11 to the ACZ-added subgroup. Baseline characteristics, including age at enrollment, leukemic subtype, HD-MTX cycle at enrollment, and anthropometric parameters, were comparable between the subgroups. The ACZ-added subgroup demonstrated a significantly higher 24-hour MTX decrement rate (79.2% vs. 74.2%; P = 0.0129), lower incidence of delayed MTX clearance (63.6% vs. 100%; P = 0.0139), and faster time to MTX normalization (3.0 vs. 5.0 days; P = 0.0047).

Conclusions

Adjunctive ACZ may facilitate MTX clearance during HD-MTX therapy. The observed improvement in MTX clearance may be attributable to the urine alkalinization effect of ACZ, although the underlying mechanism was not directly investigated in this study. Adjunctive ACZ appears to be an effective and well-tolerated strategy for pediatric patients with ALL receiving HD-MTX. Nevertheless, larger prospective studies are warranted to validate these preliminary findings.