Comparison of Methotrexate Intensification Regimens in Children and Young Adults With T-Cell ALL
As reported by Winter et al in the Journal of Clinical Oncology, findings in the Children’s Oncology Group (COG) AALL0434 trial indicate improved outcomes with a COG methotrexate intensification regimen vs a high-dose methotrexate intensification regimen in children and young adults with T-cell acute lymphoblastic leukemia (T-ALL).
Study Details
The trial had a 2 x 2 factorial design, with results of only the methotrexate randomization component reported (nelarabine component omitted). In the methotrexate randomization, patients enrolled between 2007 and 2014 received a COG-augmented Berlin-Frankfurt-Muenster (ABFM) regimen to compare the efficacies of escalating dose intravenous (IV) methotrexate without leucovorin rescue plus pegaspargase escalating dose, Capizzi-style, IV methotrexate regimen (C-MTX) vs a BFM high-dose IV methotrexate (HDMTX) plus leucovorin rescue regimen. Approximately 90% of patients, excluding 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.
Survival Outcomes
Among 1,844 eligible and evaluable patients with T-ALL, 5-year event-free survival was 83.8% and 5-year overall survival was 89.5%. Among 1,031 patients with T-ALL but without CNS3 disease or testicular leukemia, 5-year disease-free survival was 91.5% vs 85.3% for 519 receiving ABFM with C-MTX vs 512 receiving ABFM with HDMTX (P = .005). The 5-year overall survival rates were 93.7% vs 89.4% (P = .04). Patients in the C-MTX group had 32 relapses, including 6 with central nervous system (CNS) involvement; patients in the HDMTX group had 59 relapses, including 23 with CNS involvement.
The investigators concluded, “AALL0434 established that ABFM with C-MTX was superior to ABFM plus HDMTX for T-ALL in approximately 90% of patients who received [cranial radiation therapy], with later timing for those receiving HDMTX.” They noted, “The differential timing of [cranial radiation therapy] between the study arms of AALL0434 possibly affected the observed differences in [outcomes].”
The study was supported by the National Institutes of Health and by St Baldrick’s Foundation.
Stuart S. Winter, MD, of the Children’s Minnesota Cancer and Blood Disorders Program, is the corresponding author for the Journal of Clinical Oncology article.
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