Pharmacokinetics of high-dose methotrexate in infants treated for acute lymphoblastic leukemia.
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Pharmacokinetics of high-dose methotrexate in infants treated for acute lymphoblastic leukemia. / Lönnerholm, Gudmar; Valsecchi, Maria Grazia; Paola, De Lorenzo; Schrappe, Martin; Hovi, Liisa; Campbell, Myriam; Mann, Georg; Janka-Schaub, Gritta; Li, Chi-Kong; Stary, Jan; Hann, Ian; Pieters, Rob.
In: PEDIATR BLOOD CANCER, Vol. 52, No. 5, 5, 2009, p. 596-601.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Pharmacokinetics of high-dose methotrexate in infants treated for acute lymphoblastic leukemia.
AU - Lönnerholm, Gudmar
AU - Valsecchi, Maria Grazia
AU - Paola, De Lorenzo
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
Y1 - 2009
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/m(2). 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.
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/m(2). 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 52
SP - 596
EP - 601
JO - PEDIATR BLOOD CANCER
JF - PEDIATR BLOOD CANCER
SN - 1545-5009
IS - 5
M1 - 5
ER -
