Pediatric-inspired intensified therapy of adult T-ALL reveals the favorable outcome of NOTCH1/FBXW7 mutations, but not of low ERG/BAALC expression: a GRAALL study. - Université Sorbonne Paris Nord Accéder directement au contenu
Article Dans Une Revue Blood Année : 2011

Pediatric-inspired intensified therapy of adult T-ALL reveals the favorable outcome of NOTCH1/FBXW7 mutations, but not of low ERG/BAALC expression: a GRAALL study.

Thibaut Leguay
  • Fonction : Auteur
Nicolas Boissel
  • Fonction : Auteur
Agnès Buzyn
  • Fonction : Auteur
Patrice Chevallier
Norbert Vey
Emmanuelle Tavernier
  • Fonction : Auteur
Oumedaly Reman
  • Fonction : Auteur
Philippe Rousselot
Jean-Yves Cahn
  • Fonction : Auteur
Veronique Lheritier
  • Fonction : Auteur
Yves Chalandon
Hervé Dombret
Non Renseigné
  • Fonction : Auteur

Résumé

Despite recent progress in the understanding of acute lymphoblastic leukemia (T-ALL) oncogenesis, few markers are sufficiently frequent in large subgroups to allow their use in therapeutic stratification. Low ERG and BAALC expression (E/B(low)) and NOTCH1/FBXW7 (N/F) mutations have been proposed as powerful prognostic markers in large cohorts of adult T-ALL. We therefore compared the predictive prognostic value of N/F mutations versus E/B(low) in 232 adult T-ALLs enrolled in the LALA-94 and Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocols. The outcome of T-ALLs treated in the pediatric-inspired GRAALL trials was significantly superior to the LALA-94 trial. Overall, 43% and 69% of adult T-ALL patients were classified as E/B(low) and N/F mutated, respectively. Strikingly, the good prognosis of N/F mutated patients was stronger in more intensively treated, pediatric-inspired GRAALL patients. The E/B expression level did not influence the prognosis in any subgroup. N/F mutation status and the GRAALL trial were the only 2 independent factors that correlated with longer overall survival by multivariate analysis. This study demonstrates that the N/F mutational status and treatment protocol are major outcome determinants for adults with T-ALL, the benefit of pediatric inspired protocols being essentially restricted to the N/F mutated subgroup.

Domaines

Cancer

Dates et versions

hal-00777203 , version 1 (17-01-2013)

Identifiants

Citer

Raouf Ben Abdelali, Vahid Asnafi, Thibaut Leguay, Nicolas Boissel, Agnès Buzyn, et al.. Pediatric-inspired intensified therapy of adult T-ALL reveals the favorable outcome of NOTCH1/FBXW7 mutations, but not of low ERG/BAALC expression: a GRAALL study.. Blood, 2011, 118 (19), pp.5099-107. ⟨10.1182/blood-2011-02-334219⟩. ⟨hal-00777203⟩
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