Winter SS, et al. - Researchers compared two different approaches to methotrexate (MTX) intensification in T-cell acute lymphoblastic leukemia (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 in COG AALL0434. Findings revealed that approximately 90% of patients who received CRT for T-ALL exhibited superiority of COG-augmented BFM (ABFM) with C-MTX over ABFM plus HDMTX, with later timing for those receiving HDMTX.

Methods

• Using a 2 × 2 randomization, the comparison between COG-augmented BFM (ABFM) regimen with either C-MTX or HDMTX was carried out during the 8-week interim maintenance phase in COG AALL0434.
• During either the consolidation (C-MTX; second month of therapy) or delayed intensification (HDMTX; seventh month of therapy) phase, prophylactic (12 Gy) or therapeutic (18 Gy for CNS3) cranial irradiation was given to all patients with T-ALL, except for those with low-risk features.

Results

• A total of 1,895 patients were collected from 2007 to 2014.
• For all eligible, evaluable patients with T-ALL, the estimated 5-year event-free survival and overall survival rates were 83.8% (95% CI, 81.2% to 86.4%) and 89.5% (95% CI, 87.4% to 91.7%), respectively.
• ABFM with C-MTX (n = 519) or HDMTX (n = 512) was randomly received by 1,031 patients with T-ALL but without CNS3 disease or testicular leukemia.
• Findings demonstrated that, 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.
• Data showed 32 relapses experienced by patients assigned to C-MTX, six with CNS involvement, whereas 59 relapses were reported in those assigned to HDMTX, 23 with CNS involvement.