BernheimV1, Main, Exploration, bibRecord, 000096

Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia.

Identifieur interne : 000096 ( Main/Exploration ); précédent : 000095; suivant : 000097

Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia.

Auteurs : Kheira Beldjord ; Sylvie Chevret [France] ; Vahid Asnafi [France] ; Françoise Huguet [France] ; Marie-Laure Boulland [France] ; Thibaut Leguay [France] ; Xavier Thomas [France] ; Jean-Michel Cayuela ; Nathalie Grardel [France] ; Yves Chalandon [Suisse] ; Nicolas Boissel ; Beat Schaefer [Suisse] ; Eric Delabesse [France] ; Hélène Cavé [France] ; Patrice Chevallier [France] ; Agnès Buzyn [France] ; Thierry Fest [France] ; Oumedaly Reman [France] ; Jean-Paul Vernant [France] ; Véronique Lhéritier [France] ; Marie C. Béné [France] ; Marina Lafage ; Elizabeth Macintyre [France] ; Norbert Ifrah [France] ; Hervé Dombret

Source :

Blood [ 1528-0020 ] ; 2014.

RBID : pubmed:24740809

Descripteurs français

English descriptors

KwdEn :
- Adolescent, Adult, Biomarkers, Tumor (genetics), DNA Mutational Analysis, Female, Humans, Male, Middle Aged, Multicenter Studies as Topic, Neoplasm, Residual, Precursor Cell Lymphoblastic Leukemia-Lymphoma (diagnosis), Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics), Precursor Cell Lymphoblastic Leukemia-Lymphoma (mortality), Precursor Cell Lymphoblastic Leukemia-Lymphoma (pathology), Prognosis, Recurrence, Retrospective Studies, Survival Analysis, Young Adult.
MESH :
- chemical , genetics : Biomarkers, Tumor.
- diagnosis : Precursor Cell Lymphoblastic Leukemia-Lymphoma.
- genetics : Precursor Cell Lymphoblastic Leukemia-Lymphoma.
- mortality : Precursor Cell Lymphoblastic Leukemia-Lymphoma.
- pathology : Precursor Cell Lymphoblastic Leukemia-Lymphoma.
- Adolescent, Adult, DNA Mutational Analysis, Female, Humans, Male, Middle Aged, Multicenter Studies as Topic, Neoplasm, Residual, Prognosis, Recurrence, Retrospective Studies, Survival Analysis, Young Adult.

Abstract

With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by immunoglobulin/T-cell receptor minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome-negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as the primary end point. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with postinduction MRD level ≥10(-4) and unfavorable genetic characteristics (ie, MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-cell ALL). These 2 factors allowed definition of a new risk classification that is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcome in adult ALL not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and GRAALL-2005 trials. Both trials were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively.

DOI: 10.1182/blood-2014-01-547695
PubMed: 24740809

Affiliations:

Le document en format XML

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<author><name sortKey="Thomas, Xavier" sort="Thomas, Xavier" uniqKey="Thomas X" first="Xavier" last="Thomas">Xavier Thomas</name>
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<author><name sortKey="Cayuela, Jean Michel" sort="Cayuela, Jean Michel" uniqKey="Cayuela J" first="Jean-Michel" last="Cayuela">Jean-Michel Cayuela</name>
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<author><name sortKey="Grardel, Nathalie" sort="Grardel, Nathalie" uniqKey="Grardel N" first="Nathalie" last="Grardel">Nathalie Grardel</name>
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<author><name sortKey="Chalandon, Yves" sort="Chalandon, Yves" uniqKey="Chalandon Y" first="Yves" last="Chalandon">Yves Chalandon</name>
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<author><name sortKey="Boissel, Nicolas" sort="Boissel, Nicolas" uniqKey="Boissel N" first="Nicolas" last="Boissel">Nicolas Boissel</name>
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</author>
<author><name sortKey="Schaefer, Beat" sort="Schaefer, Beat" uniqKey="Schaefer B" first="Beat" last="Schaefer">Beat Schaefer</name>
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</placeName>
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<author><name sortKey="Delabesse, Eric" sort="Delabesse, Eric" uniqKey="Delabesse E" first="Eric" last="Delabesse">Eric Delabesse</name>
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</author>
<author><name sortKey="Cave, Helene" sort="Cave, Helene" uniqKey="Cave H" first="Hélène" last="Cavé">Hélène Cavé</name>
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<author><name sortKey="Chevallier, Patrice" sort="Chevallier, Patrice" uniqKey="Chevallier P" first="Patrice" last="Chevallier">Patrice Chevallier</name>
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<country xml:lang="fr">France</country>
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<placeName><region type="region">Pays de la Loire</region>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Buzyn, Agnes" sort="Buzyn, Agnes" uniqKey="Buzyn A" first="Agnès" last="Buzyn">Agnès Buzyn</name>
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</placeName>
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</author>
<author><name sortKey="Fest, Thierry" sort="Fest, Thierry" uniqKey="Fest T" first="Thierry" last="Fest">Thierry Fest</name>
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<author><name sortKey="Reman, Oumedaly" sort="Reman, Oumedaly" uniqKey="Reman O" first="Oumedaly" last="Reman">Oumedaly Reman</name>
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<placeName><region type="region">Région Normandie</region>
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</author>
<author><name sortKey="Vernant, Jean Paul" sort="Vernant, Jean Paul" uniqKey="Vernant J" first="Jean-Paul" last="Vernant">Jean-Paul Vernant</name>
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<country xml:lang="fr">France</country>
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<author><name sortKey="Lheritier, Veronique" sort="Lheritier, Veronique" uniqKey="Lheritier V" first="Véronique" last="Lhéritier">Véronique Lhéritier</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>GRAALL Coordination Office, University Hospital Lyon Sud, Lyon</wicri:regionArea>
<placeName><region type="region">Auvergne-Rhône-Alpes</region>
<region type="old region">Rhône-Alpes</region>
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</placeName>
</affiliation>
</author>
<author><name sortKey="Bene, Marie C" sort="Bene, Marie C" uniqKey="Bene M" first="Marie C" last="Béné">Marie C. Béné</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, University Hospital, Nantes, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital, Nantes</wicri:regionArea>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lafage, Marina" sort="Lafage, Marina" uniqKey="Lafage M" first="Marina" last="Lafage">Marina Lafage</name>
<affiliation><nlm:affiliation>Department of Genetics, Aix-Marseille University, Marseille, France; and.</nlm:affiliation>
<wicri:noCountry code="subField">France; and</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Macintyre, Elizabeth" sort="Macintyre, Elizabeth" uniqKey="Macintyre E" first="Elizabeth" last="Macintyre">Elizabeth Macintyre</name>
<affiliation wicri:level="3"><nlm:affiliation>Laboratory of Oncohematology, AP-HP, Hôpital Necker Enfants-Malades, University Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades, Institut National de Recherche Médicale U1151, Paris, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Oncohematology, AP-HP, Hôpital Necker Enfants-Malades, University Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades, Institut National de Recherche Médicale U1151, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ifrah, Norbert" sort="Ifrah, Norbert" uniqKey="Ifrah N" first="Norbert" last="Ifrah">Norbert Ifrah</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, University Hospital, INSERM U892/CNRS 6299, Angers, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital, INSERM U892/CNRS 6299, Angers</wicri:regionArea>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Angers</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dombret, Herve" sort="Dombret, Herve" uniqKey="Dombret H" first="Hervé" last="Dombret">Hervé Dombret</name>
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<wicri:noCountry code="no comma">Department of Hematology and.</wicri:noCountry>
</affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia.</title>
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</author>
<author><name sortKey="Chevret, Sylvie" sort="Chevret, Sylvie" uniqKey="Chevret S" first="Sylvie" last="Chevret">Sylvie Chevret</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Biostatistics, University Paris Diderot, Institut Universitaire d'Hématologie, EA-3518 and UMR-S-717, University Hospital Saint-Louis, Assistance Publique - Hôpitaux de Paris, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
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<author><name sortKey="Asnafi, Vahid" sort="Asnafi, Vahid" uniqKey="Asnafi V" first="Vahid" last="Asnafi">Vahid Asnafi</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Oncohematology, AP-HP, Hôpital Necker Enfants-Malades, University Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades, Institut National de Recherche Médicale U1151, Paris</wicri:regionArea>
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<author><name sortKey="Huguet, Francoise" sort="Huguet, Francoise" uniqKey="Huguet F" first="Françoise" last="Huguet">Françoise Huguet</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital Purpan, Toulouse</wicri:regionArea>
<placeName><region type="region">Occitanie (région administrative)</region>
<region type="old region">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Boulland, Marie Laure" sort="Boulland, Marie Laure" uniqKey="Boulland M" first="Marie-Laure" last="Boulland">Marie-Laure Boulland</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital, Rennes</wicri:regionArea>
<placeName><region type="region">Région Bretagne</region>
<region type="old region">Région Bretagne</region>
<settlement type="city">Rennes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Leguay, Thibaut" sort="Leguay, Thibaut" uniqKey="Leguay T" first="Thibaut" last="Leguay">Thibaut Leguay</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, University Hospital Haut-Lévèque, Bordeaux, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital Haut-Lévèque, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Thomas, Xavier" sort="Thomas, Xavier" uniqKey="Thomas X" first="Xavier" last="Thomas">Xavier Thomas</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, University Hospital Lyon Sud, Lyon, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital Lyon Sud, Lyon</wicri:regionArea>
<placeName><region type="region">Auvergne-Rhône-Alpes</region>
<region type="old region">Rhône-Alpes</region>
<settlement type="city">Lyon</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cayuela, Jean Michel" sort="Cayuela, Jean Michel" uniqKey="Cayuela J" first="Jean-Michel" last="Cayuela">Jean-Michel Cayuela</name>
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<wicri:noCountry code="no comma">Department of Hematology and.</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Grardel, Nathalie" sort="Grardel, Nathalie" uniqKey="Grardel N" first="Nathalie" last="Grardel">Nathalie Grardel</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, University Hospital Claude Huriez, Lille, France;</nlm:affiliation>
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<wicri:regionArea>Department of Hematology, University Hospital Claude Huriez, Lille</wicri:regionArea>
<placeName><region type="region">Hauts-de-France</region>
<region type="old region">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
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</author>
<author><name sortKey="Chalandon, Yves" sort="Chalandon, Yves" uniqKey="Chalandon Y" first="Yves" last="Chalandon">Yves Chalandon</name>
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<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Department of Hematology, University Hospital, Geneva</wicri:regionArea>
<wicri:noRegion>Geneva</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Boissel, Nicolas" sort="Boissel, Nicolas" uniqKey="Boissel N" first="Nicolas" last="Boissel">Nicolas Boissel</name>
<affiliation><nlm:affiliation>Department of Hematology and.</nlm:affiliation>
<wicri:noCountry code="no comma">Department of Hematology and.</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Schaefer, Beat" sort="Schaefer, Beat" uniqKey="Schaefer B" first="Beat" last="Schaefer">Beat Schaefer</name>
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<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Department of Hematology, University Hospital, Zürich</wicri:regionArea>
<placeName><settlement type="city">Zurich</settlement>
<region nuts="3" type="region">Canton de Zurich</region>
</placeName>
</affiliation>
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<author><name sortKey="Delabesse, Eric" sort="Delabesse, Eric" uniqKey="Delabesse E" first="Eric" last="Delabesse">Eric Delabesse</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital Purpan, Toulouse</wicri:regionArea>
<placeName><region type="region">Occitanie (région administrative)</region>
<region type="old region">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
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</affiliation>
</author>
<author><name sortKey="Cave, Helene" sort="Cave, Helene" uniqKey="Cave H" first="Hélène" last="Cavé">Hélène Cavé</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, University Hospital Robert Debré, Assistance Publique - Hôpitaux de Paris, Paris, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital Robert Debré, Assistance Publique - Hôpitaux de Paris, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Chevallier, Patrice" sort="Chevallier, Patrice" uniqKey="Chevallier P" first="Patrice" last="Chevallier">Patrice Chevallier</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, University Hospital, Nantes, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital, Nantes</wicri:regionArea>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Buzyn, Agnes" sort="Buzyn, Agnes" uniqKey="Buzyn A" first="Agnès" last="Buzyn">Agnès Buzyn</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Oncohematology, AP-HP, Hôpital Necker Enfants-Malades, University Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades, Institut National de Recherche Médicale U1151, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fest, Thierry" sort="Fest, Thierry" uniqKey="Fest T" first="Thierry" last="Fest">Thierry Fest</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, University Hospital, Rennes, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital, Rennes</wicri:regionArea>
<placeName><region type="region">Région Bretagne</region>
<region type="old region">Région Bretagne</region>
<settlement type="city">Rennes</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Reman, Oumedaly" sort="Reman, Oumedaly" uniqKey="Reman O" first="Oumedaly" last="Reman">Oumedaly Reman</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, University Hospital, Caen, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital, Caen</wicri:regionArea>
<placeName><region type="region">Région Normandie</region>
<region type="old region">Basse-Normandie</region>
<settlement type="city">Caen</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vernant, Jean Paul" sort="Vernant, Jean Paul" uniqKey="Vernant J" first="Jean-Paul" last="Vernant">Jean-Paul Vernant</name>
<affiliation wicri:level="3"><nlm:affiliation>University Hospital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>University Hospital Pitié-Salpêtrière, Assistance Publique - Hôpitaux de Paris, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
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</affiliation>
</author>
<author><name sortKey="Lheritier, Veronique" sort="Lheritier, Veronique" uniqKey="Lheritier V" first="Véronique" last="Lhéritier">Véronique Lhéritier</name>
<affiliation wicri:level="3"><nlm:affiliation>GRAALL Coordination Office, University Hospital Lyon Sud, Lyon, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>GRAALL Coordination Office, University Hospital Lyon Sud, Lyon</wicri:regionArea>
<placeName><region type="region">Auvergne-Rhône-Alpes</region>
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<author><name sortKey="Bene, Marie C" sort="Bene, Marie C" uniqKey="Bene M" first="Marie C" last="Béné">Marie C. Béné</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, University Hospital, Nantes, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital, Nantes</wicri:regionArea>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Nantes</settlement>
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</affiliation>
</author>
<author><name sortKey="Lafage, Marina" sort="Lafage, Marina" uniqKey="Lafage M" first="Marina" last="Lafage">Marina Lafage</name>
<affiliation><nlm:affiliation>Department of Genetics, Aix-Marseille University, Marseille, France; and.</nlm:affiliation>
<wicri:noCountry code="subField">France; and</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Macintyre, Elizabeth" sort="Macintyre, Elizabeth" uniqKey="Macintyre E" first="Elizabeth" last="Macintyre">Elizabeth Macintyre</name>
<affiliation wicri:level="3"><nlm:affiliation>Laboratory of Oncohematology, AP-HP, Hôpital Necker Enfants-Malades, University Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades, Institut National de Recherche Médicale U1151, Paris, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratory of Oncohematology, AP-HP, Hôpital Necker Enfants-Malades, University Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades, Institut National de Recherche Médicale U1151, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
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</author>
<author><name sortKey="Ifrah, Norbert" sort="Ifrah, Norbert" uniqKey="Ifrah N" first="Norbert" last="Ifrah">Norbert Ifrah</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, University Hospital, INSERM U892/CNRS 6299, Angers, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital, INSERM U892/CNRS 6299, Angers</wicri:regionArea>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
<settlement type="city">Angers</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dombret, Herve" sort="Dombret, Herve" uniqKey="Dombret H" first="Hervé" last="Dombret">Hervé Dombret</name>
<affiliation><nlm:affiliation>Department of Hematology and.</nlm:affiliation>
<wicri:noCountry code="no comma">Department of Hematology and.</wicri:noCountry>
</affiliation>
</author>
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<series><title level="j">Blood</title>
<idno type="eISSN">1528-0020</idno>
<imprint><date when="2014" type="published">2014</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Biomarkers, Tumor (genetics)</term>
<term>DNA Mutational Analysis</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Multicenter Studies as Topic</term>
<term>Neoplasm, Residual</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (diagnosis)</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics)</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (mortality)</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (pathology)</term>
<term>Prognosis</term>
<term>Recurrence</term>
<term>Retrospective Studies</term>
<term>Survival Analysis</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse de mutations d'ADN</term>
<term>Analyse de survie</term>
<term>Femelle</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs B et T (anatomopathologie)</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs B et T (diagnostic)</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs B et T (génétique)</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs B et T (mortalité)</term>
<term>Maladie résiduelle</term>
<term>Marqueurs biologiques tumoraux (génétique)</term>
<term>Mâle</term>
<term>Pronostic</term>
<term>Récidive</term>
<term>Études multicentriques comme sujet</term>
<term>Études rétrospectives</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Biomarkers, Tumor</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Leucémie-lymphome lymphoblastique à précurseurs B et T</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Leucémie-lymphome lymphoblastique à précurseurs B et T</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Leucémie-lymphome lymphoblastique à précurseurs B et T</term>
<term>Marqueurs biologiques tumoraux</term>
</keywords>
<keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</term>
</keywords>
<keywords scheme="MESH" qualifier="mortalité" xml:lang="fr"><term>Leucémie-lymphome lymphoblastique à précurseurs B et T</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>DNA Mutational Analysis</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Multicenter Studies as Topic</term>
<term>Neoplasm, Residual</term>
<term>Prognosis</term>
<term>Recurrence</term>
<term>Retrospective Studies</term>
<term>Survival Analysis</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse de mutations d'ADN</term>
<term>Analyse de survie</term>
<term>Femelle</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Maladie résiduelle</term>
<term>Mâle</term>
<term>Pronostic</term>
<term>Récidive</term>
<term>Études multicentriques comme sujet</term>
<term>Études rétrospectives</term>
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<front><div type="abstract" xml:lang="en">With intensified pediatric-like therapy and genetic disease dissection, the field of adult acute lymphoblastic leukemia (ALL) has evolved recently. In this new context, we aimed to reassess the value of conventional risk factors with regard to new genetic alterations and early response to therapy, as assessed by immunoglobulin/T-cell receptor minimal residual disease (MRD) levels. The study was performed in 423 younger adults with Philadelphia chromosome-negative ALL in first remission (265 B-cell precursor [BCP] and 158 T-cell ALL), with cumulative incidence of relapse (CIR) as the primary end point. In addition to conventional risk factors, the most frequent currently available genetic alterations were included in the analysis. A higher specific hazard of relapse was independently associated with postinduction MRD level ≥10(-4) and unfavorable genetic characteristics (ie, MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-cell ALL). These 2 factors allowed definition of a new risk classification that is strongly associated with higher CIR and shorter relapse-free and overall survival. These results indicate that genetic abnormalities are important predictors of outcome in adult ALL not fully recapitulated by early response to therapy. Patients included in this study were treated in the multicenter GRAALL-2003 and GRAALL-2005 trials. Both trials were registered at http://www.clinicaltrials.gov as #NCT00222027 and #NCT00327678, respectively.</div>
</front>
</TEI>
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<name sortKey="Cayuela, Jean Michel" sort="Cayuela, Jean Michel" uniqKey="Cayuela J" first="Jean-Michel" last="Cayuela">Jean-Michel Cayuela</name>
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<name sortKey="Lafage, Marina" sort="Lafage, Marina" uniqKey="Lafage M" first="Marina" last="Lafage">Marina Lafage</name>
</noCountry>
<country name="France"><region name="Île-de-France"><name sortKey="Chevret, Sylvie" sort="Chevret, Sylvie" uniqKey="Chevret S" first="Sylvie" last="Chevret">Sylvie Chevret</name>
</region>
<name sortKey="Asnafi, Vahid" sort="Asnafi, Vahid" uniqKey="Asnafi V" first="Vahid" last="Asnafi">Vahid Asnafi</name>
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<name sortKey="Boulland, Marie Laure" sort="Boulland, Marie Laure" uniqKey="Boulland M" first="Marie-Laure" last="Boulland">Marie-Laure Boulland</name>
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<name sortKey="Chevallier, Patrice" sort="Chevallier, Patrice" uniqKey="Chevallier P" first="Patrice" last="Chevallier">Patrice Chevallier</name>
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<name sortKey="Huguet, Francoise" sort="Huguet, Francoise" uniqKey="Huguet F" first="Françoise" last="Huguet">Françoise Huguet</name>
<name sortKey="Ifrah, Norbert" sort="Ifrah, Norbert" uniqKey="Ifrah N" first="Norbert" last="Ifrah">Norbert Ifrah</name>
<name sortKey="Leguay, Thibaut" sort="Leguay, Thibaut" uniqKey="Leguay T" first="Thibaut" last="Leguay">Thibaut Leguay</name>
<name sortKey="Lheritier, Veronique" sort="Lheritier, Veronique" uniqKey="Lheritier V" first="Véronique" last="Lhéritier">Véronique Lhéritier</name>
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<name sortKey="Thomas, Xavier" sort="Thomas, Xavier" uniqKey="Thomas X" first="Xavier" last="Thomas">Xavier Thomas</name>
<name sortKey="Vernant, Jean Paul" sort="Vernant, Jean Paul" uniqKey="Vernant J" first="Jean-Paul" last="Vernant">Jean-Paul Vernant</name>
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<country name="Suisse"><noRegion><name sortKey="Chalandon, Yves" sort="Chalandon, Yves" uniqKey="Chalandon Y" first="Yves" last="Chalandon">Yves Chalandon</name>
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<name sortKey="Schaefer, Beat" sort="Schaefer, Beat" uniqKey="Schaefer B" first="Beat" last="Schaefer">Beat Schaefer</name>
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Serveur d'exploration Hippolyte Bernheim

Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia.

Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia.

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	Serveur d'exploration Hippolyte Bernheim
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