Postinduction minimal residual disease predicts outcome and benefit from allogeneic stem cell transplantation in acute myeloid leukemia with NPM1 mutation: A study by the acute leukemia French association group

Marie Balsat, Aline Renneville, Xavier Thomas, Stéphane De Botton, Denis Caillot, Alice Marceau, Emilie Lemasle, Jean Pierre Marolleau, Olivier Nibourel, Céline Berthon, Emmanuel Raffoux, Arnaud Pigneux, Céline Rodriguez, Norbert Vey, Jean Michel Cayuela, Sandrine Hayette, Thorsten Braun, Marie Magdeleine Coudé, Christine Terre, Karine Celli-LebrasHervé Dombret, Claude Preudhomme, Nicolas Boissel

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

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    Résumé

    Purpose This study assessed the prognostic impact of postinduction NPM1-mutated (NPM1m) minimal residual disease (MRD) in young adult patients (age, 18 to 60 years) with acute myeloid leukemia, and addressed the question of whether NPM1m MRD may be used as a predictive factor of allogeneic stem cell transplantation (ASCT) benefit. Patients and Methods Among 229 patients with NPM1m who were treated in the Acute Leukemia French Association 0702 (ALFA-0702) trial, MRD evaluation was available in 152 patients in first remission. Patients with nonfavorable AML according to the European LeukemiaNet (ELN) classification were eligible for ASCT in first remission. Results After induction therapy, patients who did not achieve a 4-log reduction in NPM1m peripheral blood-MRD (PB-MRD) had a higher cumulative incidence of relapse (subhazard ratio [SHR], 5.83; P <.001) and a shorter overall survival (OS; hazard ratio [HR], 10.99; P <.001). In multivariable analysis, an abnormal karyotype, the presence of FLT3-internal tandem duplication (ITD), and a < 4-log reduction in PB-MRD were significantly associated with a higher relapse incidence and shorter OS. In the subset of patients with FLT3-ITD, only age, white blood cell count, and < 4-log reduction in PB-MRD, but not FLT3-ITD allelic ratio, remained of significant prognostic value. In these patients with nonfavorable AML according to European LeukemiaNet, disease-free survival and OS were significantly improved by ASCT in those with a <4-log reduction in PB-MRD. This benefit was not observed in those with a < 4-log reduction in PB-MRD, with a significant interaction between ASCT effect and PB-MRD response (P = .024 and .027 for disease-free survival and OS, respectively). Conclusion Our study supports the strong prognostic significance of early NPM1mPB-MRD, independent of the cytogenetic and molecular context. Moreover, NPM1m PB-MRD may be used as a predictive factor for ASCT indication.

    langue originaleAnglais
    Pages (de - à)185-193
    Nombre de pages9
    journalJournal of Clinical Oncology
    Volume35
    Numéro de publication2
    Les DOIs
    étatPublié - 10 janv. 2017

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