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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.

Ben Abdelali, Raouf; Asnafi, Vahid; Leguay, Thibaut; Boissel, Nicolas; Buzyn, Agnès; Chevallier, Patrice; Thomas, Xavier; Lepretre, Stephane; Huguet, Françoise; Vey, Norbert; Escoffre-Barbe, Martine; Tavernier, Emmanuelle; Reman, Oumedaly; Fegueux, Nathalie; Turlure, Pascal; Rousselot, Philippe; Cahn, Jean-Yves; Lheritier, Veronique; Chalandon, Yves; Béné, Marie-Christine; Macintyre, Elizabeth; Dombret, Hervé; Ifrah, Norbert.
Blood; 118(19): 5099-107, 2011 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-21835957
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.
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