Improved survival for children and young adults with t-lineage acute lymphoblastic leukemia: Results from the children's oncology Group AALL0434 methotrexate randomization

Stuart S. Winter, Kimberly P. Dunsmore, Meenakshi Devidas, Brent L. Wood, Natia Esiashvili, Zhiguo Chen, Nancy Eisenberg, Nikki Briegel, Robert J. Hayashi, Julie M. Gastier-Foster, Andrew J. Carroll, Nyla A. Heerema, Barbara L. Asselin, Paul S. Gaynon, Michael J. Borowitz, Mignon L. Loh, Karen R. Rabin, Elizabeth A. Raetz, Patrick A. Zweidler-Mckay, Naomi J. WinickWilliam L. Carroll, Stephen P. Hunger

Research output: Contribution to journalArticlepeer-review

Abstract

Early intensification with methotrexate (MTX) is a key component of acute lymphoblastic leukemia (ALL) therapy. Two different approaches to MTX intensification exist but had not been compared in T-cell ALL (T-ALL): The Children's Oncology Group (COG) escalating dose intravenous MTX without leucovorin rescue plus pegaspargase escalating dose, Capizzi-style, intravenous MTX (C-MTX) regimen and the Berlin-Frankfurt-Muenster (BFM) high-dose intravenous MTX (HDMTX) plus leucovorin rescue regimen. Patients and Methods COG AALL0434 included a 2 3 2 randomization that compared the COG-augmented BFM (ABFM) regimen with either C-MTX or HDMTX during the 8-week interim maintenance phase. All patients with T-ALL, except for those with low-risk features, received prophylactic (12 Gy) or therapeutic (18 Gy for CNS3) cranial irradiation during either the consolidation (C-MTX; second month of therapy) or delayed intensification (HDMTX; seventh month of therapy) phase. Results AALL0434 accrued 1,895 patients from 2007 to 2014. The 5-year event-free survival and overall survival rates for all eligible, evaluable patients with T-ALL were 83.8% (95% CI, 81.2% to 86.4%) and 89.5% (95% CI, 87.4% to 91.7%), respectively. The 1,031 patients with T-ALL but without CNS3 disease or testicular leukemia were randomly assigned to receive ABFM with C-MTX (n = 519) or HDMTX (n = 512). The estimated 5-year disease-free survival (P = .005) and overall survival (P = .04) rates were 91.5% (95% CI, 88.1% to 94.8%) and 93.7% (95% CI, 90.8% to 96.6%) for C-MTX and 85.3% (95% CI, 81.0%-89.5%) and 89.4% (95% CI, 85.7%-93.2%) for HDMTX. Patients assigned to C-MTX had 32 relapses, six with CNS involvement, whereas those assigned to HDMTX had 59 relapses, 23 with CNS involvement. Conclusion AALL0434 established that ABFM with C-MTX was superior to ABFM plus HDMTX for T-ALL in approximately 90% of patients who received CRT, with later timing for those receiving HDMTX.

Original languageEnglish (US)
Pages (from-to)2926-2934
Number of pages9
JournalJournal of Clinical Oncology
Volume36
Issue number29
DOIs
StatePublished - Oct 10 2018
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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