Abstract：
:Risk-adjusted treatment stratification in T-cell acute lymphoblastic leukemias (T-ALLs) is currently based only on early response to chemotherapy. We investigated the prognostic implication of hyperactivation of NOTCH pathway resulting from mutations of NOTCH1 or FBXW7 in children with T-ALL enrolled in EORTC-CLG trials. Overall, 80 out of 134 (60%) patients were NOTCH+ (NOTCH1 and/or FBXW7 mutated). Although clinical presentations were not significantly associated with NOTCH status, NOTCH+ patients showed a better early response to chemotherapy as compared with NOTCH- patients, according to the rate of poor pre-phase 'responders' (25% versus 44%; P=0.02) and the incidence of high minimal residual disease (MRD) levels (11% (7/62) versus 32% (10/31); P=0.01) at completion of induction. However, the outcome of NOTCH+ patients was similar to that of NOTCH- patients, with a 5-year event-free survival (EFS) of 73% and 70% (P=0.82), and 5-year overall survival of 82% and 79% (P=0.62), respectively. In patients with high MRD levels, the 5-year EFS rate was 0% (NOTCH+) versus 42% (NOTCH-), whereas in those with low MRD levels, the outcome was similar: 76% (NOTCH+) versus 78% (NOTCH-). The incidence of isolated central nervous system (CNS) relapses was relatively high in NOTCH1+ patients (8.3%), which could be related to a higher propensity of NOTCH+ leukemic blasts to target the CNS.
journal_name
Leukemiajournal_title
Leukemiaauthors
Clappier E,Collette S,Grardel N,Girard S,Suarez L,Brunie G,Kaltenbach S,Yakouben K,Mazingue F,Robert A,Boutard P,Plantaz D,Rohrlich P,van Vlierberghe P,Preudhomme C,Otten J,Speleman F,Dastugue N,Suciu S,Benoit Y,Bdoi
10.1038/leu.2010.205subject
Has Abstractpub_date
2010-12-01 00:00:00pages
2023-31issue
12eissn
0887-6924issn
1476-5551pii
leu2010205journal_volume
24pub_type
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