title: Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts and treatment outcome in children with B-progenitor-cell acute lymphoblastic leukemia: a Pediatric Oncology Group study.
abstract: We reported that children with B-progenitor-cell acute lymphoblastic leukemia (BpALL) treated in the early 1980s whose lymphoblasts accumulated high levels of methotrexate (MTX) and of methotrexate polyglutamates (MTXPGs) in vitro had an improved 5-year event-free survival (EFS) (65% (standard error (s.e.) 12%) vs 22% (s.e. 9%)). We repeated this study in children with BpALL treated in the early 1990s. The major change in treatment was the addition of 12 24-h infusions of 1 g/M2 MTX with leucovorin rescue (IDMTX). In 87 children treated on Pediatric Oncology Group (POG) study 9005 and POG 9006, the 5-year EFS for those whose lymphoblasts accumulated high levels of MTX and MTXPGs (79.2%, s.e. 8.3%) was not significantly different from that of patients with lesser accumulation of MTX and MTXPGs (77.7%, s.e. 5.4%). These findings support the notion that higher dose MTX therapy has contributed to increased cure, particularly for patients whose lymphoblasts accumulate the drug less well.
authors.affiliation: The Penny Cole Hematology Research Laboratory, McGill University - Montreal Children's Hospital Research Institute, Montreal, Quebec, Canada. vmwhitehead@citenet.net
authors.forename: V M
authors.initials: VM
authors.lastname: Whitehead
authors.forename: J J
authors.initials: JJ
authors.lastname: Shuster
authors.forename: M J
authors.initials: MJ
authors.lastname: Vuchich
authors.forename: D H
authors.initials: DH
authors.lastname: Mahoney
authors.forename: S J
authors.initials: SJ
authors.lastname: Lauer
authors.forename: C
authors.initials: C
authors.lastname: Payment
authors.forename: P A
authors.initials: PA
authors.lastname: Koch
authors.forename: L D
authors.initials: LD
authors.lastname: Cooley
authors.forename: A T
authors.initials: AT
authors.lastname: Look
authors.forename: D J
authors.initials: DJ
authors.lastname: Pullen
authors.forename: B
authors.initials: B
authors.lastname: Camitta
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D011099:Polyglutamic Acid; C014085:methotrexate polyglutamate; D008727:Methotrexate