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Comprehensive Evaluation of the Effectiveness and Safety of Placenta-Targeted Drug Delivery Using Three Complementary Methods
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Published on: September 10, 2018

Pharmacokinetics of high-dose methotrexate in infants treated for acute lymphoblastic leukemia

Gudmar Lönnerholm1, Maria Grazia Valsecchi, Paola De Lorenzo

  • 1Department of Women's and Children's Health, University Hospital, Uppsala, Sweden. gudmar.lonnerholm@kbh.uu.se

Pediatric Blood & Cancer
|January 10, 2009
PubMed

Insights

The Interfant-99 study found that current high-dose methotrexate (HD MTX) dosing rules for infants with acute lymphoblastic leukemia (ALL) are adequate. No significant impact on survival was observed with varying MTX levels or clearance rates.

Area of Science:

  • Pediatric Oncology
  • Pharmacokinetics
  • Hematology

Background:

  • The Interfant-99 protocol investigated treatment for infants with acute lymphoblastic leukemia (ALL).
  • High-dose methotrexate (HD MTX) is a key component in ALL treatment regimens.

Purpose of the Study:

  • To evaluate the pharmacokinetic variability of HD MTX in infants undergoing ALL treatment.
  • To determine the relationship between MTX levels, clearance, and treatment outcomes in this population.

Main Methods:

  • Data from 103 infants treated with HD MTX (5 g/m²) were analyzed.
  • Dosing was adjusted based on age (<6 months, 6-12 months, >12 months) and body surface area (BSA).
  • Steady-state MTX concentrations and systemic clearance were measured.

Main Results:

  • Median MTX concentration was 57.8 microM; clearance varied with age and sex (boys > girls).
  • Eight infants had MTX levels below the target of 20 microM.
  • All infants tolerated the HD MTX dose, with no significant effect on disease-free survival observed based on MTX concentration or clearance.

Conclusions:

  • Current MTX dosing rules within the Interfant-99 protocol appear appropriate.
  • Consideration may be given to increasing MTX doses for infants with sub-median plasma levels after the first dose, given suboptimal infant ALL outcomes.
Abstract

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