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

Gudmar Lönnerholm, Maria Grazia Valsecchi, Paola De Lorenzo, Martin Schrappe, Liisa Hovi, Myriam Campbell, Georg Mann, Gritta Janka-Schaub, Chi Kong Li, Jan Stary, Ian Hann, Rob Pieters

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

18 Citaten (Scopus)


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/m2. 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 mM (range 9.5-313). The median systemic clearance was 6.22 L/hr/m2 BSA, and tended to increase with age (P = 0.099). Boys had higher clearance than girls, 6.77 and 5.28 L/hr/ m2 (P = 0.030), and tended to have lower median MTX concen-tration at 24 hr. Eight infants had MTX levels below 20 mM, 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 mM. 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.

Originele taal-2Engels
Pagina's (van-tot)596-601
Aantal pagina's6
TijdschriftPediatric Blood and Cancer
Nummer van het tijdschrift5
StatusGepubliceerd - mei 2009
Extern gepubliceerdJa


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