Prognostic significance of NOTCH1/FBXW7 mutations in pediatric T cell acute lymphoblastic leukemia: a study of minimal residual disease risk-directed CCLG-ALL 2008 treatment protocol.

NOTCH1 / FBXW7 mutation is common in T-cell acute lymphoblastic leukemia (T-ALL), but controversy looms on its prognostic significance. We screened 98 pediatric T-ALL patients treated on minimal residual disease (MRD) risk-directed CCLG-ALL 2008 protocol. NOTCH1 / FBXW7 mutations were analyzed by Sanger sequencing, and MRD was evaluated by flow cytometry. In overall, 51.02 and 8.75% of patients harbored NOTCH1 and FBXW7 mutations respectively. More favorable 10-year overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were seen in NOTCH1 ^mut patients ( NOTCH1 ^mut vs. NOTCH1 ^wt , OS, 82.7 ± 5.6% vs. 62.4 ± 7.4%, p  = .020; EFS, 80.9 ± 5.8 vs. 48.4 ± 7.8%, p  = .001; DFS, 82.9 ± 5.6 vs. 52.9 ± 7.7%, p  = .001). NOTCH1 gene status and MRD post-induction were identified as independent prognostic factors. A combination of NOTCH1 gene status and MRD could distinguish patients with NOTCH1 mutations and MRD < 1 × 10 ^-4 with 100% OS, EFS, and DFS. These results indicated NOTCH1 mutation predicted a favorable outcome in pediatric T-ALL and may be considered a risk stratification factor.