Standard Versus Reduced Hydration to Improve Elimination of High-Dose Methotrexate in Pediatric Patients: A Controlled Crossover Trial.

Background: Hydration and urine alkalinization are the mainstays for the prevention of methotrexate-induced nephrotoxicity. Current oncology protocols recommend pediatric patients who are administered high-dose methotrexate (HDMTX) to be aggressively hydrated with an alkaline solution, which may lead to overhydration. This pilot study sought to determine whether reduced posthydration results in a shorter time to methotrexate elimination without increasing adverse effects.
Methods: A prospective randomized controlled crossover study design of pediatric patients with acute lymphoblastic leukemia was performed. Patients were randomized to begin with standard or reduced volume intravenous fluids. Over the course of four cycles of HDMTX, patients alternated between the standard rate of 125 mL/m ² /h and a reduced volume rate of 62.5 mL/m ² /h. The primary endpoint was the time from the start of HDMTX to a serum methotrexate concentration less than 0.1 µmol/L.
Results: Data from 37 HDMTX courses were analyzed in 10 patients aged 1-17 years. The median time to methotrexate elimination was similar between the standard and reduced hydration regimens at 71.7 h (60.8-115.6 h) versus 72.9 h (59.9-132 h, p value = 0.6539). There was no difference in the change from baseline to maximum creatinine (10% vs. 18.9%, p value = 0.6566), maximum weight gain (0.7 kg vs. 0.4 kg, p value = 0.0967), or rates of severe mucositis between hydration regimens.
Conclusion: Reduced posthydration appeared to be safe and provided similar time to HDMTX elimination. A multicenter study is indicated to confirm the use of reduced hydration to optimize supportive care in pediatric patients administered HDMTX.
Trial Registration: NCT03964259.
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