TY - JOUR
T1 - Pharmacokinetics of high-dose methotrexate in infants treated for acute lymphoblastic leukemia
AU - Lönnerholm, Gudmar
AU - Valsecchi, Maria Grazia
AU - De Lorenzo, Paola
AU - Schrappe, Martin
AU - Hovi, Liisa
AU - Campbell, Myriam
AU - Mann, Georg
AU - Janka-Schaub, Gritta
AU - Li, Chi Kong
AU - Stary, Jan
AU - Hann, Ian
AU - Pieters, Rob
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
KW - ALL
KW - Infants
KW - Methotrexate
KW - Pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=63649141531&partnerID=8YFLogxK
U2 - 10.1002/pbc.21925
DO - 10.1002/pbc.21925
M3 - Article
C2 - 19132729
AN - SCOPUS:63649141531
SN - 1545-5009
VL - 52
SP - 596
EP - 601
JO - Pediatric Blood and Cancer
JF - Pediatric Blood and Cancer
IS - 5
ER -