BernheimV1, Main, Exploration, bibRecord, 000062

Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia.

Identifieur interne : 000062 ( Main/Exploration ); précédent : 000061; suivant : 000063

Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia.

Auteurs : Nathalie Dhédin [France] ; Anne Huynh [France] ; Sébastien Maury [France] ; Reza Tabrizi [France] ; Kheira Beldjord [France] ; Vahid Asnafi [France] ; Xavier Thomas [France] ; Patrice Chevallier [France] ; Stéphanie Nguyen [France] ; Valérie Coiteux [France] ; Jean-Henri Bourhis [France] ; Yosr Hichri [France] ; Martine Escoffre-Barbe [France] ; Oumedaly Reman [France] ; Carlos Graux [Belgique] ; Yves Chalandon [Suisse] ; Didier Blaise [France] ; Urs Schanz [Suisse] ; Véronique Lhéritier [France] ; Jean-Yves Cahn ; Hervé Dombret [France] ; Norbert Ifrah [France]

Source :

Blood [ 1528-0020 ] ; 2015.

RBID : pubmed:25587040

Descripteurs français

English descriptors

KwdEn :
- Adolescent, Adult, Clinical Trials as Topic, Disease-Free Survival, Female, Humans, Male, Middle Aged, Multivariate Analysis, Neoplasm, Residual, Outcome Assessment (Health Care) (methods), Philadelphia Chromosome, Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics), Precursor Cell Lymphoblastic Leukemia-Lymphoma (therapy), Remission Induction, Stem Cell Transplantation (methods), Transplantation, Homologous, Young Adult.
MESH :
- genetics : Precursor Cell Lymphoblastic Leukemia-Lymphoma.
- methods : Outcome Assessment (Health Care), Stem Cell Transplantation.
- therapy : Precursor Cell Lymphoblastic Leukemia-Lymphoma.
- Adolescent, Adult, Clinical Trials as Topic, Disease-Free Survival, Female, Humans, Male, Middle Aged, Multivariate Analysis, Neoplasm, Residual, Philadelphia Chromosome, Remission Induction, Transplantation, Homologous, Young Adult.

Abstract

Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL-2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at least 1 conventional high-risk factor were candidates for SCT in first complete remission. Among these, 282 (54%) received a transplant in first complete remission. At 3 years, posttransplant cumulative incidences of relapse, nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%, 15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a significant difference in RFS between SCT and no-SCT cohorts. However, SCT was associated with longer RFS in patients with postinduction minimal residual disease (MRD) ≥10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B-cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion (hazard ratio, 0.42). This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as #NCT00222027; GRAALL-2005 was registered as #NCT00327678.

DOI: 10.1182/blood-2014-09-599894
PubMed: 25587040

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="Nguyen, Stephanie" sort="Nguyen, Stephanie" uniqKey="Nguyen S" first="Stéphanie" last="Nguyen">Stéphanie Nguyen</name>
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<author><name sortKey="Escoffre Barbe, Martine" sort="Escoffre Barbe, Martine" uniqKey="Escoffre Barbe M" first="Martine" last="Escoffre-Barbe">Martine Escoffre-Barbe</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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<country xml:lang="fr">France</country>
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<placeName><region type="region">Région Normandie</region>
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<author><name sortKey="Graux, Carlos" sort="Graux, Carlos" uniqKey="Graux C" first="Carlos" last="Graux">Carlos Graux</name>
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<country xml:lang="fr">Belgique</country>
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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="Schanz, Urs" sort="Schanz, Urs" uniqKey="Schanz U" first="Urs" last="Schanz">Urs Schanz</name>
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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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<wicri:noRegion>Pierre Bénite</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cahn, Jean Yves" sort="Cahn, Jean Yves" uniqKey="Cahn J" first="Jean-Yves" last="Cahn">Jean-Yves Cahn</name>
<affiliation><nlm:affiliation>Department of Hematology, University Hospital, Grenoble, France; and.</nlm:affiliation>
<wicri:noCountry code="subField">France; and</wicri:noCountry>
</affiliation>
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<author><name sortKey="Dombret, Herve" sort="Dombret, Herve" uniqKey="Dombret H" first="Hervé" last="Dombret">Hervé Dombret</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology and University Paris Diderot, Institut Universitaire d'Hématologie, EA-3518, University Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology and University Paris Diderot, Institut Universitaire d'Hématologie, EA-3518, 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="Ifrah, Norbert" sort="Ifrah, Norbert" uniqKey="Ifrah N" first="Norbert" last="Ifrah">Norbert Ifrah</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology and INSERM U 892/CNRS 6299, University Hospital, Angers, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology and INSERM U 892/CNRS 6299, University Hospital, Angers</wicri:regionArea>
<placeName><region type="region">Pays de la Loire</region>
<region type="old region">Pays de la Loire</region>
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<author><name sortKey="Maury, Sebastien" sort="Maury, Sebastien" uniqKey="Maury S" first="Sébastien" last="Maury">Sébastien Maury</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital Henri Mondor, AP-HP, Créteil</wicri:regionArea>
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<author><name sortKey="Tabrizi, Reza" sort="Tabrizi, Reza" uniqKey="Tabrizi R" first="Reza" last="Tabrizi">Reza Tabrizi</name>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
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<author><name sortKey="Beldjord, Kheira" sort="Beldjord, Kheira" uniqKey="Beldjord K" first="Kheira" last="Beldjord">Kheira Beldjord</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology and University Paris Diderot, Institut Universitaire d'Hématologie, EA-3518, University Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
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<region type="old 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>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, University Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades, INSERM U1151, and Onco-Hematology Laboratory, Assistance Publique Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades, INSERM U1151, and Onco-Hematology Laboratory, Assistance Publique Hôpitaux de Paris, Hôpital Necker-Enfants Malades, 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><name sortKey="Thomas, Xavier" sort="Thomas, Xavier" uniqKey="Thomas X" first="Xavier" last="Thomas">Xavier Thomas</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Hematology, Hospital Lyon Sud, Pierre Bénite, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, Hospital Lyon Sud, Pierre Bénite</wicri:regionArea>
<wicri:noRegion>Pierre Bénite</wicri:noRegion>
<wicri:noRegion>Pierre Bénite</wicri:noRegion>
</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="Nguyen, Stephanie" sort="Nguyen, Stephanie" uniqKey="Nguyen S" first="Stéphanie" last="Nguyen">Stéphanie Nguyen</name>
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<wicri:regionArea>Department of Hematology, Institut Gustave Roussy, Villejuif</wicri:regionArea>
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<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, University Hospital, Montpellier</wicri:regionArea>
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<region type="old region">Languedoc-Roussillon</region>
<settlement type="city">Montpellier</settlement>
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<author><name sortKey="Escoffre Barbe, Martine" sort="Escoffre Barbe, Martine" uniqKey="Escoffre Barbe M" first="Martine" last="Escoffre-Barbe">Martine Escoffre-Barbe</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>
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<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>
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</affiliation>
</author>
<author><name sortKey="Graux, Carlos" sort="Graux, Carlos" uniqKey="Graux C" first="Carlos" last="Graux">Carlos Graux</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Hematology, University Hospital, Yvoir, Belgium;</nlm:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Department of Hematology, University Hospital, Yvoir</wicri:regionArea>
<wicri:noRegion>Yvoir</wicri:noRegion>
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</author>
<author><name sortKey="Chalandon, Yves" sort="Chalandon, Yves" uniqKey="Chalandon Y" first="Yves" last="Chalandon">Yves Chalandon</name>
<affiliation wicri:level="3"><nlm:affiliation>Division of Hematology, Department of Medical Specialties, University Hospital, Geneva, and Faculty of Medicine, University of Geneva Switzerland and Swiss Group for Clinical Cancer Research, Bern, Switzerland;</nlm:affiliation>
<country xml:lang="fr">Suisse</country>
<wicri:regionArea>Division of Hematology, Department of Medical Specialties, University Hospital, Geneva, and Faculty of Medicine, University of Geneva Switzerland and Swiss Group for Clinical Cancer Research, Bern</wicri:regionArea>
<placeName><settlement type="city">Berne</settlement>
<region type="région" nuts="3">Canton de Berne</region>
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<author><name sortKey="Blaise, Didier" sort="Blaise, Didier" uniqKey="Blaise D" first="Didier" last="Blaise">Didier Blaise</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology, Institut Paoli Calmettes, Marseille, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology, Institut Paoli Calmettes, Marseille</wicri:regionArea>
<placeName><region type="region">Provence-Alpes-Côte d'Azur</region>
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<author><name sortKey="Schanz, Urs" sort="Schanz, Urs" uniqKey="Schanz U" first="Urs" last="Schanz">Urs Schanz</name>
<affiliation wicri:level="1"><nlm:affiliation>Division of Hematology, University Hospital of Zurich, Zurich, Switzerland;</nlm:affiliation>
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<wicri:regionArea>Division of Hematology, University Hospital of Zurich, Zurich</wicri:regionArea>
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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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<author><name sortKey="Cahn, Jean Yves" sort="Cahn, Jean Yves" uniqKey="Cahn J" first="Jean-Yves" last="Cahn">Jean-Yves Cahn</name>
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<author><name sortKey="Dombret, Herve" sort="Dombret, Herve" uniqKey="Dombret H" first="Hervé" last="Dombret">Hervé Dombret</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Hematology and University Paris Diderot, Institut Universitaire d'Hématologie, EA-3518, University Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France;</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology and University Paris Diderot, Institut Universitaire d'Hématologie, EA-3518, University Hospital Saint-Louis, 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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</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 and INSERM U 892/CNRS 6299, University Hospital, Angers, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Hematology and INSERM U 892/CNRS 6299, University Hospital, 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>
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<series><title level="j">Blood</title>
<idno type="eISSN">1528-0020</idno>
<imprint><date when="2015" type="published">2015</date>
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<term>Adult</term>
<term>Clinical Trials as Topic</term>
<term>Disease-Free Survival</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Multivariate Analysis</term>
<term>Neoplasm, Residual</term>
<term>Outcome Assessment (Health Care) (methods)</term>
<term>Philadelphia Chromosome</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (genetics)</term>
<term>Precursor Cell Lymphoblastic Leukemia-Lymphoma (therapy)</term>
<term>Remission Induction</term>
<term>Stem Cell Transplantation (methods)</term>
<term>Transplantation, Homologous</term>
<term>Young Adult</term>
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<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse multivariée</term>
<term>Chromosome Philadelphie</term>
<term>Essais cliniques comme sujet</term>
<term>Femelle</term>
<term>Humains</term>
<term>Induction de rémission</term>
<term>Jeune adulte</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs B et T ()</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs B et T (génétique)</term>
<term>Maladie résiduelle</term>
<term>Mâle</term>
<term>Survie sans rechute</term>
<term>Transplantation de cellules souches ()</term>
<term>Transplantation homologue</term>
<term>Évaluation de résultat (soins) ()</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>
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<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Outcome Assessment (Health Care)</term>
<term>Stem Cell Transplantation</term>
</keywords>
<keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Precursor Cell Lymphoblastic Leukemia-Lymphoma</term>
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<keywords scheme="MESH" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Clinical Trials as Topic</term>
<term>Disease-Free Survival</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Multivariate Analysis</term>
<term>Neoplasm, Residual</term>
<term>Philadelphia Chromosome</term>
<term>Remission Induction</term>
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<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 multivariée</term>
<term>Chromosome Philadelphie</term>
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<term>Femelle</term>
<term>Humains</term>
<term>Induction de rémission</term>
<term>Jeune adulte</term>
<term>Leucémie-lymphome lymphoblastique à précurseurs B et T</term>
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<front><div type="abstract" xml:lang="en">Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL-2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at least 1 conventional high-risk factor were candidates for SCT in first complete remission. Among these, 282 (54%) received a transplant in first complete remission. At 3 years, posttransplant cumulative incidences of relapse, nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%, 15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a significant difference in RFS between SCT and no-SCT cohorts. However, SCT was associated with longer RFS in patients with postinduction minimal residual disease (MRD) ≥10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B-cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion (hazard ratio, 0.42). This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as #NCT00222027; GRAALL-2005 was registered as #NCT00327678.</div>
</front>
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Serveur d'exploration Hippolyte Bernheim

Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia.

Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia.

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	Serveur d'exploration Hippolyte Bernheim
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