Pharmacokinetics of high-dose methotrexate in infants treated for acute lymphoblastic 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/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/m2BSA, 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.
|Keywords||ALL, Infants, Methotrexate, Pharmacokinetics|
|Persistent URL||dx.doi.org/10.1002/pbc.21925, hdl.handle.net/1765/24109|
|Journal||Pediatric Blood & Cancer|
Lönnerholm, G, Valsecchi, M.G, de Lorenzo, P, Schrappe, M, Hovi, L, Campbell, M, … Pieters, R. (2009). Pharmacokinetics of high-dose methotrexate in infants treated for acute lymphoblastic leukemia. Pediatric Blood & Cancer, 52(5), 596–601. doi:10.1002/pbc.21925