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Bouvier, Anne;
Hamel, Jean‐François;
Delaunay, Jacques;
Delabesse, Eric;
Dumas, Pierre‐Yves;
Ledoux, Marie‐Pierre;
Peterlin, Pierre;
Luquet, Isabelle;
Roth Guepin, Gabrielle;
Bulabois, Claude Eric;
Gallego Hernanz, Maria Pilar;
Guillerm, Gaëlle;
Guieze, Romain;
Hicheri, Yosr;
Simand, Célestine;
Himberlin, Chantal;
Hunault‐Berger, Mathilde;
Bernard, Marc;
Jourdan, Eric;
Caillot, Denis;
Dorvaux, Véronique;
Tavernier, Emmanuelle;
Daguindau, Etienne;
Banos, Anne;
[...]
Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate‐risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006‐intermediate‐risk trial
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- Medientyp: E-Artikel
- Titel: Molecular classification and prognosis in younger adults with acute myeloid leukemia and intermediate‐risk cytogenetics treated or not by gemtuzumab ozogamycin: Final results of the GOELAMS/FILO acute myeloid leukemia 2006‐intermediate‐risk trial
- Beteiligte: Bouvier, Anne; Hamel, Jean‐François; Delaunay, Jacques; Delabesse, Eric; Dumas, Pierre‐Yves; Ledoux, Marie‐Pierre; Peterlin, Pierre; Luquet, Isabelle; Roth Guepin, Gabrielle; Bulabois, Claude Eric; Gallego Hernanz, Maria Pilar; Guillerm, Gaëlle; Guieze, Romain; Hicheri, Yosr; Simand, Célestine; Himberlin, Chantal; Hunault‐Berger, Mathilde; Bernard, Marc; Jourdan, Eric; Caillot, Denis; Dorvaux, Véronique; Tavernier, Emmanuelle; Daguindau, Etienne; Banos, Anne; [...]
- Erschienen: Wiley, 2021
- Erschienen in: European Journal of Haematology
- Umfang: 111-121
- Sprache: Englisch
- DOI: 10.1111/ejh.13626
- ISSN: 0902-4441; 1600-0609
- Schlagwörter: Hematology ; General Medicine
- Zusammenfassung: <jats:title>Abstract</jats:title><jats:p>In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m<jats:sup>2</jats:sup> of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with <jats:italic>de novo</jats:italic> acute myeloid leukemia (AML) and intermediate‐risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event‐free survival nor overall survival were improved by GO in younger AML patients (<60 years) ineligible for allogeneic stem‐cell transplantation. (<jats:italic>P</jats:italic> = .086; <jats:italic>P</jats:italic> = .149, respectively). Using unsupervised hierarchical clustering based on mutational analysis of seven genes (<jats:italic>NPM1</jats:italic>, <jats:italic>FLT3</jats:italic>‐ITD, <jats:italic>CEBPA</jats:italic>, <jats:italic>DNMT3A</jats:italic>, <jats:italic>IDH1</jats:italic>, <jats:italic>IDH2</jats:italic>, and <jats:italic>ASXL1</jats:italic>), six clusters of patients with significant different outcome were identified. Five clusters were based on <jats:italic>FLT3</jats:italic>‐ITD, <jats:italic>NPM1</jats:italic>, and <jats:italic>CEBPA</jats:italic> mutations as well as epigenetic modifiers (<jats:italic>DNMT3A</jats:italic>, <jats:italic>IDH1/2</jats:italic>, <jats:italic>ASXL1</jats:italic>), whereas the last cluster, representing 25% of patients, had no mutation and intermediate risk. One cluster isolated <jats:italic>FLT3</jats:italic>‐ITD mutations with higher allelic ratio and a very poor outcome. The addition of GO had no impact in these molecular clusters. Although not conclusive for GO impact in AML patients <60 years, this study provides a molecular classification that distinguishes six AML clusters influencing prognosis in younger AML patients with intermediate‐risk cytogenetic.</jats:p>
- Beschreibung: <jats:title>Abstract</jats:title><jats:p>In this randomized phase 3 study, the FILO group tested whether the addition of 6 mg/m<jats:sup>2</jats:sup> of gemtuzumab ozogamycin (GO) to standard chemotherapy could improve outcome of younger patients with <jats:italic>de novo</jats:italic> acute myeloid leukemia (AML) and intermediate‐risk cytogenetics. GO arm was prematurely closed after 254 inclusions because of toxicity. A similar complete remission rate was observed in both arms. Neither event‐free survival nor overall survival were improved by GO in younger AML patients (<60 years) ineligible for allogeneic stem‐cell transplantation. (<jats:italic>P</jats:italic> = .086; <jats:italic>P</jats:italic> = .149, respectively). Using unsupervised hierarchical clustering based on mutational analysis of seven genes (<jats:italic>NPM1</jats:italic>, <jats:italic>FLT3</jats:italic>‐ITD, <jats:italic>CEBPA</jats:italic>, <jats:italic>DNMT3A</jats:italic>, <jats:italic>IDH1</jats:italic>, <jats:italic>IDH2</jats:italic>, and <jats:italic>ASXL1</jats:italic>), six clusters of patients with significant different outcome were identified. Five clusters were based on <jats:italic>FLT3</jats:italic>‐ITD, <jats:italic>NPM1</jats:italic>, and <jats:italic>CEBPA</jats:italic> mutations as well as epigenetic modifiers (<jats:italic>DNMT3A</jats:italic>, <jats:italic>IDH1/2</jats:italic>, <jats:italic>ASXL1</jats:italic>), whereas the last cluster, representing 25% of patients, had no mutation and intermediate risk. One cluster isolated <jats:italic>FLT3</jats:italic>‐ITD mutations with higher allelic ratio and a very poor outcome. The addition of GO had no impact in these molecular clusters. Although not conclusive for GO impact in AML patients <60 years, this study provides a molecular classification that distinguishes six AML clusters influencing prognosis in younger AML patients with intermediate‐risk cytogenetic.</jats:p>
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