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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  NOTCH1mut  patients ( NOTCH1mutvs. NOTCH1wt , 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 &lt; 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.

leukemia and lymphoma

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