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Title

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

Authors
Ben Abdelali, Raouf
Asnafi, Vahid
Leguay, Thibaut
Boissel, Nicolas
Buzyn, Agnès
Chevallier, Patrice
Thomas, Xavier
Lepretre, Stephane
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Published in Blood. 2011, vol. 118, no. 19, p. 5099-107
Abstract 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.
Keywords AdolescentAdultCell Cycle Proteins/geneticsChildClinical ProtocolsDisease-Free SurvivalF-Box Proteins/geneticsFemaleGene ExpressionHumansKaplan-Meier EstimateLeukemia-Lymphoma, Adult T-Cell/classification/drug therapy/geneticsMaleMiddle AgedMutationNeoplasm Proteins/geneticsPredictive Value of TestsPrognosisProspective StudiesReceptor, Notch1/geneticsTrans-Activators/geneticsTreatment OutcomeUbiquitin-Protein Ligases/geneticsYoung Adult
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PMID: 21835957
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BEN ABDELALI, Raouf 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. In: Blood, 2011, vol. 118, n° 19, p. 5099-107. doi: 10.1182/blood-2011-02-334219 https://archive-ouverte.unige.ch/unige:25852

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Deposited on : 2013-01-22

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