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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.
AuthorsV M Whitehead, J J Shuster, M J Vuchich, D H Mahoney Jr, S J Lauer, C Payment, P A Koch, L D Cooley, A T Look, D J Pullen, B Camitta
JournalLeukemia (Leukemia) Vol. 19 Issue 4 Pg. 533-6 (Apr 2005) ISSN: 0887-6924 [Print] England
PMID15716987 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antimetabolites, Antineoplastic
  • Polyglutamic Acid
  • methotrexate polyglutamate
  • Methotrexate
Topics
  • Antimetabolites, Antineoplastic (administration & dosage, pharmacokinetics, therapeutic use)
  • B-Lymphocytes (pathology)
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cells (pathology)
  • Humans
  • Male
  • Methotrexate (administration & dosage, analogs & derivatives, pharmacokinetics, therapeutic use)
  • Polyglutamic Acid (administration & dosage, analogs & derivatives, pharmacokinetics)
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, mortality)
  • Survival Rate
  • Treatment Outcome

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