Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: A report from the Children's Oncology Group

Yousif Matloub, Bruce C. Bostrom, Stephen P. Hunger, Linda C. Stork, Anne Angiolillo, Harland Sather, Mei La, Julie M. Gastier-Foster, Nyla A. Heerema, Scott Sailer, Patrick J. Buckley, Blythe Thomson, Catherine Cole, James B. Nachman, Gregory Reaman, Naomi Winick, William L. Carroll, Meenakshi Devidas, Paul S. Gaynon

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83 Scopus citations

Abstract

Children's Cancer Group-1991 selected 2 components from the Children's Cancer Group studies shown to be effective in high-risk acute lymphoblastic leukemia and examined them in children with National Cancer Institute standard-risk acute B-precursor lymphoblastic leukemia. These were (1) vincristine and escalating IV methotrexate (MTX) without leucovorin rescue during the interim maintenance (IM) phases and (2) addition of a second delayed intensification (DI) phase. Eligible patients (n = 2078) were randomly assigned to regimens containing either oral (PO) MTX, PO mercaptopurine, dexamethasone, and vincristine or IV MTX during IM phases, and regimens with either single DI or double DI. Five-year event-free survival (EFS) and overall survival for patients on the PO MTX arms were 88.7% ± 1.4% and 96% ± 0.9% versus 92.6% ± 1.2% and 96.5% ± 0.8% for those on the IV MTX arms (P = .009, P = .66). Five-year EFS and overall survival for patients who received single DI were 90.9% ± 1.3% and 97.1% ± 0.8% versus 90.5% ± 1.3% and 95.4% ± 3.8% for those who received double DI (P = .71, P = .12). No advantage was found for a second DI; however, replacement of PO MTX, PO mercaptopurine, vincristine, and dexamethasone during IM with vincristine and escalating IV MTX improved EFS.

Original languageEnglish (US)
Pages (from-to)243-251
Number of pages9
JournalBlood
Volume118
Issue number2
DOIs
StatePublished - Jul 14 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Matloub, Y., Bostrom, B. C., Hunger, S. P., Stork, L. C., Angiolillo, A., Sather, H., La, M., Gastier-Foster, J. M., Heerema, N. A., Sailer, S., Buckley, P. J., Thomson, B., Cole, C., Nachman, J. B., Reaman, G., Winick, N., Carroll, W. L., Devidas, M., & Gaynon, P. S. (2011). Escalating intravenous methotrexate improves event-free survival in children with standard-risk acute lymphoblastic leukemia: A report from the Children's Oncology Group. Blood, 118(2), 243-251. https://doi.org/10.1182/blood-2010-12-322909