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Pharmacokinetics of high‐dose methotrexate in infants treated for acute lymphoblastic leukemia
Author(s) -
Lönnerholm Gudmar,
Valsecchi Maria Grazia,
De Lorenzo Paola,
Schrappe Martin,
Hovi Liisa,
Campbell Myriam,
Mann Georg,
JankaSchaub Gritta,
Li ChiKong,
Stary Jan,
Hann Ian,
Pieters Rob
Publication year - 2009
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.21925
Subject(s) - medicine , methotrexate , dosing , body surface area , pharmacokinetics , lymphoblastic leukemia , acute lymphocytic leukemia , gastroenterology , pediatrics , leukemia
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 µM (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 µM, 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 µM. 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. Pediatr Blood Cancer 2009;52:596–601. © 2009 Wiley‐Liss, Inc.