Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia in Remission.
Identifieur interne : 000C41 ( PubMed/Checkpoint ); précédent : 000C40; suivant : 000C42Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia in Remission.
Auteurs : Kristin M. Page [États-Unis] ; Myriam Labopin [France] ; Annalisa Ruggeri [Monaco] ; Gerard Michel [France] ; Cristina Diaz De Heredia [Espagne] ; Tracey O'Brien [Australie] ; Alessandra Picardi [Italie] ; Mouhab Ayas [Arabie saoudite] ; Henrique Bittencourt [Canada] ; Ajay J. Vora [Royaume-Uni] ; Jesse Troy [États-Unis] ; Carmen Bonfim [Brésil] ; Fernanda Volt [Monaco] ; Eliane Gluckman [Monaco] ; Peter Bader [Allemagne] ; Joanne Kurtzberg [États-Unis] ; Vanderson Rocha [Royaume-Uni]Source :
- Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [ 1523-6536 ] ; 2017.
Abstract
For pediatric patients with acute lymphoblastic leukemia (ALL), relapse is an important cause of treatment failure after unrelated cord blood transplant (UCBT). Compared with other donor sources, relapse is similar or even reduced after UCBT despite less graft-versus-host disease (GVHD). We performed a retrospective analysis to identify risk factors associated with the 5-year cumulative incidence of relapse after UCBT. In this retrospective, registry-based study, we examined the outcomes of 640 children (<18 years) with ALL in first complete remission (CR1; n = 257, 40%) or second complete remission (CR2; n = 383, 60%) who received myeloablative conditioning followed by a single-unit UCBT from 2000 to 2012. Most received antithymocyte globulin (88%) or total body irradiation (TBI; 69%), and cord blood grafts were primarily mismatched at 1 (50%) or 2(+) (34%) HLA loci. Considering patients in CR1, the rates of 5-year overall survival (OS), leukemia-free survival (LFS), and relapse were 59%, 52%, and 23%, respectively. In multivariate analysis (MVA), acute GVHD (grades II to IV) and TBI protected against relapse. In patients in CR2, rates of 5-year OS, LFS, and the cumulative incidence of relapse were 46%, 44%, and 28%, respectively. In MVA, longer duration from diagnosis to UCBT (≥30 months) and TBI were associated with decreased relapse risk. Importantly, receiving a fully HLA matched graft was a strong risk factor for increased relapse in MVA. An exploratory analysis of all 640 patients supported the important association between the presence of acute GVHD and less relapse but also demonstrated an increased risk of nonrelapse mortality. In conclusion, the impact of GVHD as a graft-versus-leukemia marker is evident in pediatric ALL after UCBT. Strategies that promote graft-versus-leukemia while harnessing GVHD should be further investigated.
DOI: 10.1016/j.bbmt.2017.04.015
PubMed: 28438676
Affiliations:
- Allemagne, Arabie saoudite, Australie, Brésil, Canada, Espagne, France, Italie, Monaco, Royaume-Uni, États-Unis
- Angleterre, Caroline du Nord, Catalogne, District de Darmstadt, Grand Londres, Hesse (Land), Latium, Oxfordshire, Provence-Alpes-Côte d'Azur, Québec, Île-de-France
- Barcelone, Francfort-sur-le-Main, Londres, Marseille, Montréal, Oxford, Paris, Rome
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Electronic address: kristin.page@duke.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Labopin, Myriam" sort="Labopin, Myriam" uniqKey="Labopin M" first="Myriam" last="Labopin">Myriam Labopin</name><affiliation wicri:level="3"><nlm:affiliation>EBMT, Acute Leukemia Working Party, Service d'hematologie et therapie cellulaire, Hôpital Saint Antoine, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EBMT, Acute Leukemia Working Party, Service d'hematologie et therapie cellulaire, Hôpital Saint Antoine, 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="Ruggeri, Annalisa" sort="Ruggeri, Annalisa" uniqKey="Ruggeri A" first="Annalisa" last="Ruggeri">Annalisa Ruggeri</name><affiliation wicri:level="1"><nlm:affiliation>EBMT, Acute Leukemia Working Party, Service d'hematologie et therapie cellulaire, Hôpital Saint Antoine, Paris, France; Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco.</nlm:affiliation><country xml:lang="fr">Monaco</country><wicri:regionArea>EBMT, Acute Leukemia Working Party, Service d'hematologie et therapie cellulaire, Hôpital Saint Antoine, Paris, France; Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville</wicri:regionArea><wicri:noRegion>Monaco-Ville</wicri:noRegion></affiliation></author><author><name sortKey="Michel, Gerard" sort="Michel, Gerard" uniqKey="Michel G" first="Gerard" last="Michel">Gerard Michel</name><affiliation wicri:level="3"><nlm:affiliation>Timone Enfants Hospital and Aix-Marseille University, Department of Pediatric Hematology and Oncology, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Timone Enfants Hospital and Aix-Marseille University, Department of Pediatric Hematology and Oncology, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Diaz De Heredia, Cristina" sort="Diaz De Heredia, Cristina" uniqKey="Diaz De Heredia C" first="Cristina" last="Diaz De Heredia">Cristina Diaz De Heredia</name><affiliation wicri:level="3"><nlm:affiliation>Servicio de Hematologia y Oncologia Pediatrica, Hospital Vall d'Hebron, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Servicio de Hematologia y Oncologia Pediatrica, Hospital Vall d'Hebron, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="O Brien, Tracey" sort="O Brien, Tracey" uniqKey="O Brien T" first="Tracey" last="O'Brien">Tracey O'Brien</name><affiliation wicri:level="1"><nlm:affiliation>Blood and Marrow Transplant Program, Sydney Children's Hospital, Randwick, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Blood and Marrow Transplant Program, Sydney Children's Hospital, Randwick, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Picardi, Alessandra" sort="Picardi, Alessandra" uniqKey="Picardi A" first="Alessandra" last="Picardi">Alessandra Picardi</name><affiliation wicri:level="3"><nlm:affiliation>University of Tor Vergata, Rome Transplant Network, Rome, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>University of Tor Vergata, Rome Transplant Network, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Ayas, Mouhab" sort="Ayas, Mouhab" uniqKey="Ayas M" first="Mouhab" last="Ayas">Mouhab Ayas</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.</nlm:affiliation><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea>Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital & Research Center, Riyadh</wicri:regionArea><wicri:noRegion>Riyadh</wicri:noRegion></affiliation></author><author><name sortKey="Bittencourt, Henrique" sort="Bittencourt, Henrique" uniqKey="Bittencourt H" first="Henrique" last="Bittencourt">Henrique Bittencourt</name><affiliation wicri:level="3"><nlm:affiliation>Hematology/Bone Marrow Transplantation, Hopital Saint Justine, Montreal, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Hematology/Bone Marrow Transplantation, Hopital Saint Justine, Montreal</wicri:regionArea><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Vora, Ajay J" sort="Vora, Ajay J" uniqKey="Vora A" first="Ajay J" last="Vora">Ajay J. Vora</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pediatric Haematology, The Children's Hospital, Sheffield, UK; Department of Haematology and Oncology, Great Ormond Street Hospital, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Pediatric Haematology, The Children's Hospital, Sheffield, UK; Department of Haematology and Oncology, Great Ormond Street Hospital, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Troy, Jesse" sort="Troy, Jesse" uniqKey="Troy J" first="Jesse" last="Troy">Jesse Troy</name><affiliation wicri:level="2"><nlm:affiliation>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, North Carolina.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Bonfim, Carmen" sort="Bonfim, Carmen" uniqKey="Bonfim C" first="Carmen" last="Bonfim">Carmen Bonfim</name><affiliation wicri:level="1"><nlm:affiliation>Hospital Das Clinicas, Universidade Federal do Parana, Curitiba, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Hospital Das Clinicas, Universidade Federal do Parana, Curitiba</wicri:regionArea><wicri:noRegion>Curitiba</wicri:noRegion></affiliation></author><author><name sortKey="Volt, Fernanda" sort="Volt, Fernanda" uniqKey="Volt F" first="Fernanda" last="Volt">Fernanda Volt</name><affiliation wicri:level="1"><nlm:affiliation>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco.</nlm:affiliation><country xml:lang="fr">Monaco</country><wicri:regionArea>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville</wicri:regionArea><wicri:noRegion>Monaco-Ville</wicri:noRegion></affiliation></author><author><name sortKey="Gluckman, Eliane" sort="Gluckman, Eliane" uniqKey="Gluckman E" first="Eliane" last="Gluckman">Eliane Gluckman</name><affiliation wicri:level="1"><nlm:affiliation>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco.</nlm:affiliation><country xml:lang="fr">Monaco</country><wicri:regionArea>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville</wicri:regionArea><wicri:noRegion>Monaco-Ville</wicri:noRegion></affiliation></author><author><name sortKey="Bader, Peter" sort="Bader, Peter" uniqKey="Bader P" first="Peter" last="Bader">Peter Bader</name><affiliation wicri:level="3"><nlm:affiliation>Division for Stem Cell Transplantation and Immunology, Hospital for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division for Stem Cell Transplantation and Immunology, Hospital for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt am Main</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Darmstadt</region><settlement type="city">Francfort-sur-le-Main</settlement></placeName></affiliation></author><author><name sortKey="Kurtzberg, Joanne" sort="Kurtzberg, Joanne" uniqKey="Kurtzberg J" first="Joanne" last="Kurtzberg">Joanne Kurtzberg</name><affiliation wicri:level="2"><nlm:affiliation>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, North Carolina.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Rocha, Vanderson" sort="Rocha, Vanderson" uniqKey="Rocha V" first="Vanderson" last="Rocha">Vanderson Rocha</name><affiliation wicri:level="3"><nlm:affiliation>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco; Hospital Das Clinicas, University of Sao Paulo, Sao Paulo, Brazil; Churchill Hospital, Oxford University, Oxford, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco; Hospital Das Clinicas, University of Sao Paulo, Sao Paulo, Brazil; Churchill Hospital, Oxford University, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28438676</idno><idno type="pmid">28438676</idno><idno type="doi">10.1016/j.bbmt.2017.04.015</idno><idno type="wicri:Area/PubMed/Corpus">000840</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000840</idno><idno type="wicri:Area/PubMed/Curation">000837</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000837</idno><idno type="wicri:Area/PubMed/Checkpoint">000837</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000837</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia in Remission.</title><author><name sortKey="Page, Kristin M" sort="Page, Kristin M" uniqKey="Page K" first="Kristin M" last="Page">Kristin M. Page</name><affiliation wicri:level="2"><nlm:affiliation>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, North Carolina. Electronic address: kristin.page@duke.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Labopin, Myriam" sort="Labopin, Myriam" uniqKey="Labopin M" first="Myriam" last="Labopin">Myriam Labopin</name><affiliation wicri:level="3"><nlm:affiliation>EBMT, Acute Leukemia Working Party, Service d'hematologie et therapie cellulaire, Hôpital Saint Antoine, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>EBMT, Acute Leukemia Working Party, Service d'hematologie et therapie cellulaire, Hôpital Saint Antoine, 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="Ruggeri, Annalisa" sort="Ruggeri, Annalisa" uniqKey="Ruggeri A" first="Annalisa" last="Ruggeri">Annalisa Ruggeri</name><affiliation wicri:level="1"><nlm:affiliation>EBMT, Acute Leukemia Working Party, Service d'hematologie et therapie cellulaire, Hôpital Saint Antoine, Paris, France; Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco.</nlm:affiliation><country xml:lang="fr">Monaco</country><wicri:regionArea>EBMT, Acute Leukemia Working Party, Service d'hematologie et therapie cellulaire, Hôpital Saint Antoine, Paris, France; Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville</wicri:regionArea><wicri:noRegion>Monaco-Ville</wicri:noRegion></affiliation></author><author><name sortKey="Michel, Gerard" sort="Michel, Gerard" uniqKey="Michel G" first="Gerard" last="Michel">Gerard Michel</name><affiliation wicri:level="3"><nlm:affiliation>Timone Enfants Hospital and Aix-Marseille University, Department of Pediatric Hematology and Oncology, Marseille, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Timone Enfants Hospital and Aix-Marseille University, Department of Pediatric Hematology and Oncology, Marseille</wicri:regionArea><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Diaz De Heredia, Cristina" sort="Diaz De Heredia, Cristina" uniqKey="Diaz De Heredia C" first="Cristina" last="Diaz De Heredia">Cristina Diaz De Heredia</name><affiliation wicri:level="3"><nlm:affiliation>Servicio de Hematologia y Oncologia Pediatrica, Hospital Vall d'Hebron, Barcelona, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Servicio de Hematologia y Oncologia Pediatrica, Hospital Vall d'Hebron, Barcelona</wicri:regionArea><placeName><settlement type="city">Barcelone</settlement><region nuts="2" type="region">Catalogne</region></placeName></affiliation></author><author><name sortKey="O Brien, Tracey" sort="O Brien, Tracey" uniqKey="O Brien T" first="Tracey" last="O'Brien">Tracey O'Brien</name><affiliation wicri:level="1"><nlm:affiliation>Blood and Marrow Transplant Program, Sydney Children's Hospital, Randwick, New South Wales, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Blood and Marrow Transplant Program, Sydney Children's Hospital, Randwick, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Picardi, Alessandra" sort="Picardi, Alessandra" uniqKey="Picardi A" first="Alessandra" last="Picardi">Alessandra Picardi</name><affiliation wicri:level="3"><nlm:affiliation>University of Tor Vergata, Rome Transplant Network, Rome, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>University of Tor Vergata, Rome Transplant Network, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Ayas, Mouhab" sort="Ayas, Mouhab" uniqKey="Ayas M" first="Mouhab" last="Ayas">Mouhab Ayas</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.</nlm:affiliation><country xml:lang="fr">Arabie saoudite</country><wicri:regionArea>Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital & Research Center, Riyadh</wicri:regionArea><wicri:noRegion>Riyadh</wicri:noRegion></affiliation></author><author><name sortKey="Bittencourt, Henrique" sort="Bittencourt, Henrique" uniqKey="Bittencourt H" first="Henrique" last="Bittencourt">Henrique Bittencourt</name><affiliation wicri:level="3"><nlm:affiliation>Hematology/Bone Marrow Transplantation, Hopital Saint Justine, Montreal, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Hematology/Bone Marrow Transplantation, Hopital Saint Justine, Montreal</wicri:regionArea><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Vora, Ajay J" sort="Vora, Ajay J" uniqKey="Vora A" first="Ajay J" last="Vora">Ajay J. Vora</name><affiliation wicri:level="3"><nlm:affiliation>Department of Pediatric Haematology, The Children's Hospital, Sheffield, UK; Department of Haematology and Oncology, Great Ormond Street Hospital, London, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Pediatric Haematology, The Children's Hospital, Sheffield, UK; Department of Haematology and Oncology, Great Ormond Street Hospital, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Troy, Jesse" sort="Troy, Jesse" uniqKey="Troy J" first="Jesse" last="Troy">Jesse Troy</name><affiliation wicri:level="2"><nlm:affiliation>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, North Carolina.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Bonfim, Carmen" sort="Bonfim, Carmen" uniqKey="Bonfim C" first="Carmen" last="Bonfim">Carmen Bonfim</name><affiliation wicri:level="1"><nlm:affiliation>Hospital Das Clinicas, Universidade Federal do Parana, Curitiba, Brazil.</nlm:affiliation><country xml:lang="fr">Brésil</country><wicri:regionArea>Hospital Das Clinicas, Universidade Federal do Parana, Curitiba</wicri:regionArea><wicri:noRegion>Curitiba</wicri:noRegion></affiliation></author><author><name sortKey="Volt, Fernanda" sort="Volt, Fernanda" uniqKey="Volt F" first="Fernanda" last="Volt">Fernanda Volt</name><affiliation wicri:level="1"><nlm:affiliation>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco.</nlm:affiliation><country xml:lang="fr">Monaco</country><wicri:regionArea>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville</wicri:regionArea><wicri:noRegion>Monaco-Ville</wicri:noRegion></affiliation></author><author><name sortKey="Gluckman, Eliane" sort="Gluckman, Eliane" uniqKey="Gluckman E" first="Eliane" last="Gluckman">Eliane Gluckman</name><affiliation wicri:level="1"><nlm:affiliation>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco.</nlm:affiliation><country xml:lang="fr">Monaco</country><wicri:regionArea>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville</wicri:regionArea><wicri:noRegion>Monaco-Ville</wicri:noRegion></affiliation></author><author><name sortKey="Bader, Peter" sort="Bader, Peter" uniqKey="Bader P" first="Peter" last="Bader">Peter Bader</name><affiliation wicri:level="3"><nlm:affiliation>Division for Stem Cell Transplantation and Immunology, Hospital for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division for Stem Cell Transplantation and Immunology, Hospital for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt am Main</wicri:regionArea><placeName><region type="land" nuts="1">Hesse (Land)</region><region type="district" nuts="2">District de Darmstadt</region><settlement type="city">Francfort-sur-le-Main</settlement></placeName></affiliation></author><author><name sortKey="Kurtzberg, Joanne" sort="Kurtzberg, Joanne" uniqKey="Kurtzberg J" first="Joanne" last="Kurtzberg">Joanne Kurtzberg</name><affiliation wicri:level="2"><nlm:affiliation>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, North Carolina.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Rocha, Vanderson" sort="Rocha, Vanderson" uniqKey="Rocha V" first="Vanderson" last="Rocha">Vanderson Rocha</name><affiliation wicri:level="3"><nlm:affiliation>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco; Hospital Das Clinicas, University of Sao Paulo, Sao Paulo, Brazil; Churchill Hospital, Oxford University, Oxford, UK.</nlm:affiliation><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco; Hospital Das Clinicas, University of Sao Paulo, Sao Paulo, Brazil; Churchill Hospital, Oxford University, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region></placeName></affiliation></author></analytic><series><title level="j">Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation</title><idno type="eISSN">1523-6536</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">For pediatric patients with acute lymphoblastic leukemia (ALL), relapse is an important cause of treatment failure after unrelated cord blood transplant (UCBT). Compared with other donor sources, relapse is similar or even reduced after UCBT despite less graft-versus-host disease (GVHD). We performed a retrospective analysis to identify risk factors associated with the 5-year cumulative incidence of relapse after UCBT. In this retrospective, registry-based study, we examined the outcomes of 640 children (<18 years) with ALL in first complete remission (CR1; n = 257, 40%) or second complete remission (CR2; n = 383, 60%) who received myeloablative conditioning followed by a single-unit UCBT from 2000 to 2012. Most received antithymocyte globulin (88%) or total body irradiation (TBI; 69%), and cord blood grafts were primarily mismatched at 1 (50%) or 2(+) (34%) HLA loci. Considering patients in CR1, the rates of 5-year overall survival (OS), leukemia-free survival (LFS), and relapse were 59%, 52%, and 23%, respectively. In multivariate analysis (MVA), acute GVHD (grades II to IV) and TBI protected against relapse. In patients in CR2, rates of 5-year OS, LFS, and the cumulative incidence of relapse were 46%, 44%, and 28%, respectively. In MVA, longer duration from diagnosis to UCBT (≥30 months) and TBI were associated with decreased relapse risk. Importantly, receiving a fully HLA matched graft was a strong risk factor for increased relapse in MVA. An exploratory analysis of all 640 patients supported the important association between the presence of acute GVHD and less relapse but also demonstrated an increased risk of nonrelapse mortality. In conclusion, the impact of GVHD as a graft-versus-leukemia marker is evident in pediatric ALL after UCBT. Strategies that promote graft-versus-leukemia while harnessing GVHD should be further investigated.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">28438676</PMID><DateCreated><Year>2017</Year><Month>04</Month><Day>25</Day></DateCreated><DateRevised><Year>2017</Year><Month>08</Month><Day>26</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1523-6536</ISSN><JournalIssue CitedMedium="Internet"><Volume>23</Volume><Issue>8</Issue><PubDate><Year>2017</Year><Month>Aug</Month></PubDate></JournalIssue><Title>Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation</Title><ISOAbbreviation>Biol. Blood Marrow Transplant.</ISOAbbreviation></Journal><ArticleTitle>Factors Associated with Long-Term Risk of Relapse after Unrelated Cord Blood Transplantation in Children with Acute Lymphoblastic Leukemia in Remission.</ArticleTitle><Pagination><MedlinePgn>1350-1358</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S1083-8791(17)30424-X</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.bbmt.2017.04.015</ELocationID><Abstract><AbstractText>For pediatric patients with acute lymphoblastic leukemia (ALL), relapse is an important cause of treatment failure after unrelated cord blood transplant (UCBT). Compared with other donor sources, relapse is similar or even reduced after UCBT despite less graft-versus-host disease (GVHD). We performed a retrospective analysis to identify risk factors associated with the 5-year cumulative incidence of relapse after UCBT. In this retrospective, registry-based study, we examined the outcomes of 640 children (<18 years) with ALL in first complete remission (CR1; n = 257, 40%) or second complete remission (CR2; n = 383, 60%) who received myeloablative conditioning followed by a single-unit UCBT from 2000 to 2012. Most received antithymocyte globulin (88%) or total body irradiation (TBI; 69%), and cord blood grafts were primarily mismatched at 1 (50%) or 2(+) (34%) HLA loci. Considering patients in CR1, the rates of 5-year overall survival (OS), leukemia-free survival (LFS), and relapse were 59%, 52%, and 23%, respectively. In multivariate analysis (MVA), acute GVHD (grades II to IV) and TBI protected against relapse. In patients in CR2, rates of 5-year OS, LFS, and the cumulative incidence of relapse were 46%, 44%, and 28%, respectively. In MVA, longer duration from diagnosis to UCBT (≥30 months) and TBI were associated with decreased relapse risk. Importantly, receiving a fully HLA matched graft was a strong risk factor for increased relapse in MVA. An exploratory analysis of all 640 patients supported the important association between the presence of acute GVHD and less relapse but also demonstrated an increased risk of nonrelapse mortality. In conclusion, the impact of GVHD as a graft-versus-leukemia marker is evident in pediatric ALL after UCBT. Strategies that promote graft-versus-leukemia while harnessing GVHD should be further investigated.</AbstractText><CopyrightInformation>Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Page</LastName><ForeName>Kristin M</ForeName><Initials>KM</Initials><AffiliationInfo><Affiliation>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, North Carolina. Electronic address: kristin.page@duke.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Labopin</LastName><ForeName>Myriam</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>EBMT, Acute Leukemia Working Party, Service d'hematologie et therapie cellulaire, Hôpital Saint Antoine, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ruggeri</LastName><ForeName>Annalisa</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>EBMT, Acute Leukemia Working Party, Service d'hematologie et therapie cellulaire, Hôpital Saint Antoine, Paris, France; Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Michel</LastName><ForeName>Gerard</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Timone Enfants Hospital and Aix-Marseille University, Department of Pediatric Hematology and Oncology, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Diaz de Heredia</LastName><ForeName>Cristina</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Servicio de Hematologia y Oncologia Pediatrica, Hospital Vall d'Hebron, Barcelona, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>O'Brien</LastName><ForeName>Tracey</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Blood and Marrow Transplant Program, Sydney Children's Hospital, Randwick, New South Wales, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Picardi</LastName><ForeName>Alessandra</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>University of Tor Vergata, Rome Transplant Network, Rome, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ayas</LastName><ForeName>Mouhab</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Pediatric Hematology/Oncology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bittencourt</LastName><ForeName>Henrique</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Hematology/Bone Marrow Transplantation, Hopital Saint Justine, Montreal, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vora</LastName><ForeName>Ajay J</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>Department of Pediatric Haematology, The Children's Hospital, Sheffield, UK; Department of Haematology and Oncology, Great Ormond Street Hospital, London, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Troy</LastName><ForeName>Jesse</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, North Carolina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bonfim</LastName><ForeName>Carmen</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Hospital Das Clinicas, Universidade Federal do Parana, Curitiba, Brazil.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Volt</LastName><ForeName>Fernanda</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gluckman</LastName><ForeName>Eliane</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bader</LastName><ForeName>Peter</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Division for Stem Cell Transplantation and Immunology, Hospital for Children and Adolescents, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kurtzberg</LastName><ForeName>Joanne</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Division of Pediatric Blood and Marrow Transplantation, Duke University Medical Center, Durham, North Carolina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rocha</LastName><ForeName>Vanderson</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Eurocord, Hospital Saint Louis APHP, University Paris-Diderot, Paris, France; Monacord, Centre Scientifique de Monaco, Monaco-Ville, Monaco; Hospital Das Clinicas, University of Sao Paulo, Sao Paulo, Brazil; Churchill Hospital, Oxford University, Oxford, UK.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>K23 HL104575</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>04</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Biol Blood Marrow Transplant</MedlineTA><NlmUniqueID>9600628</NlmUniqueID><ISSNLinking>1083-8791</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>Blood. 2011 Jul 14;118(2):223-30</RefSource><PMID Version="1">21613256</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Clin Invest. 2014 Jul;124(7):3121-8</RefSource><PMID Version="1">24911148</PMID></CommentsCorrections><CommentsCorrections 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PubStatus="accepted"><Year>2017</Year><Month>04</Month><Day>16</Day></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2018</Year><Month>08</Month><Day>01</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>4</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>4</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>4</Month><Day>26</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28438676</ArticleId><ArticleId IdType="pii">S1083-8791(17)30424-X</ArticleId><ArticleId IdType="doi">10.1016/j.bbmt.2017.04.015</ArticleId><ArticleId IdType="pmc">PMC5569913</ArticleId><ArticleId IdType="mid">NIHMS887061</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Allemagne</li><li>Arabie saoudite</li><li>Australie</li><li>Brésil</li><li>Canada</li><li>Espagne</li><li>France</li><li>Italie</li><li>Monaco</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Angleterre</li><li>Caroline du Nord</li><li>Catalogne</li><li>District de Darmstadt</li><li>Grand Londres</li><li>Hesse (Land)</li><li>Latium</li><li>Oxfordshire</li><li>Provence-Alpes-Côte d'Azur</li><li>Québec</li><li>Île-de-France</li></region><settlement><li>Barcelone</li><li>Francfort-sur-le-Main</li><li>Londres</li><li>Marseille</li><li>Montréal</li><li>Oxford</li><li>Paris</li><li>Rome</li></settlement></list><tree><country name="États-Unis"><region name="Caroline du Nord"><name sortKey="Page, Kristin M" sort="Page, Kristin M" uniqKey="Page K" first="Kristin M" last="Page">Kristin M. Page</name></region><name sortKey="Kurtzberg, Joanne" sort="Kurtzberg, Joanne" uniqKey="Kurtzberg J" first="Joanne" last="Kurtzberg">Joanne Kurtzberg</name><name sortKey="Troy, Jesse" sort="Troy, Jesse" uniqKey="Troy J" first="Jesse" last="Troy">Jesse Troy</name></country><country name="France"><region name="Île-de-France"><name sortKey="Labopin, Myriam" sort="Labopin, Myriam" uniqKey="Labopin M" first="Myriam" last="Labopin">Myriam Labopin</name></region><name sortKey="Michel, Gerard" sort="Michel, Gerard" uniqKey="Michel G" first="Gerard" last="Michel">Gerard Michel</name></country><country name="Monaco"><noRegion><name sortKey="Ruggeri, Annalisa" sort="Ruggeri, Annalisa" uniqKey="Ruggeri A" first="Annalisa" last="Ruggeri">Annalisa Ruggeri</name></noRegion><name sortKey="Gluckman, Eliane" sort="Gluckman, Eliane" uniqKey="Gluckman E" first="Eliane" last="Gluckman">Eliane Gluckman</name><name sortKey="Volt, Fernanda" sort="Volt, Fernanda" uniqKey="Volt F" first="Fernanda" last="Volt">Fernanda Volt</name></country><country name="Espagne"><region name="Catalogne"><name sortKey="Diaz De Heredia, Cristina" sort="Diaz De Heredia, Cristina" uniqKey="Diaz De Heredia C" first="Cristina" last="Diaz De Heredia">Cristina Diaz De Heredia</name></region></country><country name="Australie"><noRegion><name sortKey="O Brien, Tracey" sort="O Brien, Tracey" uniqKey="O Brien T" first="Tracey" last="O'Brien">Tracey O'Brien</name></noRegion></country><country name="Italie"><region name="Latium"><name sortKey="Picardi, Alessandra" sort="Picardi, Alessandra" uniqKey="Picardi A" first="Alessandra" last="Picardi">Alessandra Picardi</name></region></country><country name="Arabie saoudite"><noRegion><name sortKey="Ayas, Mouhab" sort="Ayas, Mouhab" uniqKey="Ayas M" first="Mouhab" last="Ayas">Mouhab Ayas</name></noRegion></country><country name="Canada"><region name="Québec"><name sortKey="Bittencourt, Henrique" sort="Bittencourt, Henrique" uniqKey="Bittencourt H" first="Henrique" last="Bittencourt">Henrique Bittencourt</name></region></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Vora, Ajay J" sort="Vora, Ajay J" uniqKey="Vora A" first="Ajay J" last="Vora">Ajay J. Vora</name></region><name sortKey="Rocha, Vanderson" sort="Rocha, Vanderson" uniqKey="Rocha V" first="Vanderson" last="Rocha">Vanderson Rocha</name></country><country name="Brésil"><noRegion><name sortKey="Bonfim, Carmen" sort="Bonfim, Carmen" uniqKey="Bonfim C" first="Carmen" last="Bonfim">Carmen Bonfim</name></noRegion></country><country name="Allemagne"><region name="Hesse (Land)"><name sortKey="Bader, Peter" sort="Bader, Peter" uniqKey="Bader P" first="Peter" last="Bader">Peter Bader</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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