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Pharmacokinetics of high-dose methotrexate in infants treated for acute lymphoblastic leukemia
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. (Barnonkologisk forskning/Pfeifer)
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2009 (English)In: Pediatric Blood & Cancer, ISSN 1545-5009, Vol. 52, no 5, 596-601 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Interfant-99 was an international collaborative treatment protocol for infants with acute lymphoblastic leukemia (ALL). PROCEDURE: We collected data on 103 infants at the time of their first treatment with high-dose methotrexate (HD MTX), 5 g/m(2). Children <6 months of age received two-third of the calculated dose based on body surface area (BSA), children 6-12 months three-fourth of the calculated dose, and children >12 months full dose. RESULTS: The median steady-state MTX concentration at the end of the 24-hr infusion was 57.8 microM (range 9.5-313). The median systemic clearance was 6.22 L/hr/m(2) BSA, and tended to increase with age (P = 0.099). Boys had higher clearance than girls, 6.77 and 5.28 L/hr/m(2) (P = 0.030), and tended to have lower median MTX concentration at 24 hr. Eight infants had MTX levels below 20 microM, a level judged to be sufficient in B-lineage ALL in children >1 year of age. All infants tolerated the dose well enough to receive a second dose of HD MTX without dose reduction. We found no significant effect on disease-free survival for MTX steady-state concentration, MTX clearance, or time to MTX below 0.2 microM. CONCLUSIONS: Our data provide no support for a change in the dosing rules for MTX used in Interfant-99. However, in view of the poor treatment results for infants, one might consider increase in the dose for patients who reach plasma levels below median after the first MTX dose.

Place, publisher, year, edition, pages
2009. Vol. 52, no 5, 596-601 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-103268DOI: 10.1002/pbc.21925ISI: 000264168800010PubMedID: 19132729OAI: oai:DiVA.org:uu-103268DiVA: diva2:217902
Available from: 2009-05-18 Created: 2009-05-18 Last updated: 2009-07-22Bibliographically approved

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