High-dose methotrexate therapy of childhood acute lymphoblastic leukemia: lack of relation between serum methotrexate concentration and creatinine clearance.
BACKGROUND
The objectives of this study were: (1) to analyze the relation of serum methotrexate (MTX) concentration with creatinine clearance, (2) to compare the leucovorin rescue dose administered to the patients based on creatinine clearance, with the one calculated according to serum MTX levels, and (3) to determine MTX-related toxicity.


METHODS
Thirty children with high-risk non-B acute lymphoblastic leukemia (ALL) treated according to the national protocol (PINDA 92) based on ALL BFM 90, were randomized to receive consolidation with four doses of either 1 or 2 g/m(2) MTX as a 24-hr infusion, at 2-week intervals (group M1 and M2, respectively). Serum MTX concentrations were measured at 24, 42, and 48 hr after beginning the infusion and were analyzed retrospectively. The creatinine clearance was calculated after 12-hr intravenous hydration prior to each MTX dose. Leucovorin dosage was adjusted according to creatinine clearance.


RESULTS
Serum MTX concentrations at 24, 42, and 48 hr after starting the infusion were not related to creatinine clearance in both treatment groups. Leucovorin rescue administered according to creatinine clearance was excessive in 43% in group M1 and in 51% in group M2, as compared to the dose calculated according to serum MTX levels. No serious clinical complications were observed.


CONCLUSIONS
These results suggest that creatinine clearance is not a good parameter to calculate leucovorin rescue. MTX-related toxicity in this group of patients receiving a dose of 1 or 2 g/m(2) and rescued with leucovorin without monitoring serum MTX levels was acceptable.
Joannon
Pilar
P
Division of Pediatric Hematology-Oncology, Hospital Roberto del Río, University of Chile, Santiago, Chile. pilarjoannon@yahoo.com
Oviedo
Iris
I
Campbell
Myriam
M
Tordecilla
Juan
J
D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D002677:Chile / Q000453:epidemiology; D003401:Creatine / Q000097:blood*; D018572:Disease-Free Survival; D016903:Drug Monitoring; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control; D006801:Humans; D007223:Infant; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008657:Metabolic Clearance Rate; D008727:Methotrexate / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D009061:Mouth Mucosa; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D013280:Stomatitis / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control
D000964:Antimetabolites, Antineoplastic; D003401:Creatine; D002955:Leucovorin; D008727:Methotrexate