Effectiveness of high-dose methotrexate in T-cell lymphoblastic leukemia and advanced-stage lymphoblastic lymphoma: a randomized study by the Children's Oncology Group (POG 9404)

The Pediatric Oncology Group (POG) phase 3 trial 9404 was designed to determine the effectiveness of high-dose methotrexate (HDM) when added to multi-agent chemotherapy based on the Dana-Farber backbone. Children with T-cell acute lymphoblastic leukemia (T-ALL) or advanced lymphoblastic lymphoma (T-NHL) were randomized at diagnosis to receive/not receive HDM (5 g/m(2) as a 24-hour infusion) at weeks 4, 7, 10, and 13. Between 1996 and 2000, 436 patients were enrolled in the methotrexate randomization. Five-year and 10-year event-free survival (EFS) was 80.2% +/- 2.8% and 78.1% +/- 4.3% for HDM (n = 219) versus 73.6% +/- 3.1% and 72.6% +/- 5.0% for no HDM (n = 217; P = .17). For T-ALL, 5-year and 10-year EFS was significantly better with HDM(n = 148, 5 years: 79.5% +/- 3.4%, 10 years: 77.3% +/- 5.3%) versus no HDM (n = 151, 5 years: 67.5% +/- 3.9%, 10 years: 66.0% +/- 6.6%; P = .047). The difference in EFS between HDM and no HDM was not significant for T-NHL patients (n = 71, 5 years: 81.7% +/- 4.9%, 10 years: 79.9% +/- 7.5% vs n = 66, 5 years: 87.8% +/- 4.2%, 10 years: 87.8% +/- 6.4%; P = .38). The frequency of mucositis was significantly higher in patients treated with HDM (P = .003). The results support adding HDM to the treatment of children with T-ALL, but not with NHL, despite the increased risk of mucositis. (Blood. 2011;118(4):874-883)