Author: "Centre d'investigation clinique en cancérologie (CI2C)" - Searchworks@Jio Institute Digital Library Search Results

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42 results on '"Centre d'investigation clinique en cancérologie (CI2C)"'

1. Contribution of Tore Supra in preparation of ITER

Author: B. Saoutic, J. Abiteboul, L. Allegretti, S. Allfrey, J.M. Ané, T. Aniel, A. Argouarch, J.F. Artaud, M.H. Aumenier, S. Balme, V. Basiuk, O. Baulaigue, P. Bayetti, A. Bécoulet, M. Bécoulet, M.S. Benkadda, F. Benoit, G. Berger-by, J.M. Bernard, B. Bertrand, P. Beyer, A. Bigand, J. Blum, D. Boilson, G. Bonhomme, H. Bottollier-Curtet, C. Bouchand, F. Bouquey, C. Bourdelle, S. Bourmaud, C. Brault, S. Brémond, C. Brosset, J. Bucalossi, Y. Buravand, P. Cara, V. Catherine-Dumont, A. Casati, M. Chantant, M. Chatelier, G. Chevet, D. Ciazynski, G. Ciraolo, F. Clairet, M. Coatanea-Gouachet, L. Colas, L. Commin, E. Corbel, Y. Corre, X. Courtois, R. Dachicourt, M. Dapena Febrer, M. Davi Joanny, R. Daviot, H. De Esch, J. Decker, P. Decool, P. Delaporte, E. Delchambre, E. Delmas, L. Delpech, C. Desgranges, P. Devynck, T. Dittmar, L. Doceul, D. Douai, H. Dougnac, J.L. Duchateau, B. Dugué, N. Dumas, R. Dumont, A. Durocher, F.X. Duthoit, A. Ekedahl, D. Elbeze, M. El Khaldi, F. Escourbiac, F. Faisse, G. Falchetto, M. Farge, J.L. Farjon, M. Faury, N. Fedorczak, C. Fenzi-Bonizec, M. Firdaouss, Y. Frauel, X. Garbet, J. Garcia, J.L. Gardarein, L. Gargiulo, P. Garibaldi, E. Gauthier, O. Gaye, A. Géraud, M. Geynet, P. Ghendrih, I. Giacalone, S. Gibert, C. Gil, G. Giruzzi, M. Goniche, V. Grandgirard, C. Grisolia, G. Gros, A. Grosman, R. Guigon, D. Guilhem, B. Guillerminet, R. Guirlet, J. Gunn, O. Gurcan, S. Hacquin, J.C. Hatchressian, P. Hennequin, C. Hernandez, P. Hertout, S. Heuraux, J. Hillairet, G.T. Hoang, C. Honore, M. Houry, T. Hutter, P. Huynh, G. Huysmans, F. Imbeaux, E. Joffrin, J. Johner, L. Jourd'Heuil, Y.S. Katharria, D. Keller, S.H. Kim, M. Kocan, M. Kubic, B. Lacroix, V. Lamaison, G. Latu, Y. Lausenaz, C. Laviron, F. Leroux, L. Letellier, M. Lipa, X. Litaudon, T. Loarer, P. Lotte, S. Madeleine, P. Magaud, P. Maget, R. Magne, L. Manenc, Y. Marandet, G. Marbach, J.L. Maréchal, L. Marfisi, C. Martin, G. Martin, V. Martin, A. Martinez, J.P. Martins, R. Masset, D. Mazon, N. Mellet, L. Mercadier, A. Merle, D. Meshcheriakov, O. Meyer, L. Million, M. Missirlian, P. Mollard, V. Moncada, P. Monier-Garbet, D. Moreau, P. Moreau, L. Morini, M. Nannini, M. Naiim Habib, E. Nardon, H. Nehme, C. Nguyen, S. Nicollet, R. Nouilletas, T. Ohsako, M. Ottaviani, S. Pamela, H. Parrat, P. Pastor, A.L. Pecquet, B. Pégourié, Y. Peysson, I. Porchy, C. Portafaix, M. Preynas, M. Prou, J.M. Raharijaona, N. Ravenel, C. Reux, P. Reynaud, M. Richou, H. Roche, P. Roubin, R. Sabot, F. Saint-Laurent, S. Salasca, F. Samaille, A. Santagiustina, Y. Sarazin, A. Semerok, J. Schlosser, M. Schneider, M. Schubert, F. Schwander, J.L. Ségui, G. Selig, P. Sharma, J. Signoret, A. Simonin, S. Song, E. Sonnendruker, F. Sourbier, P. Spuig, P. Tamain, M. Tena, J.M. Theis, D. Thouvenin, A. Torre, J.M. Travère, E. Tsitrone, J.C. Vallet, E. Van Der Plas, A. Vatry, J.M. Verger, L. Vermare, F. Villecroze, D. Villegas, R. Volpe, K. Vulliez, J. Wagrez, T. Wauters, L. Zani, D. Zarzoso, X.L. Zou, Institut de Recherche sur la Fusion par confinement Magnétique (IRFM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Science et Ingénierie des Matériaux et Procédés (SIMaP), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut National Polytechnique de Grenoble (INPG)-Centre National de la Recherche Scientifique (CNRS), Dept. Accelerateurs - XFEL, Laboratoire de l'Accélérateur Linéaire (LAL), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Laboratoire de Météorologie Dynamique (UMR 8539) (LMD), Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École des Ponts ParisTech (ENPC)-École polytechnique (X)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Institut universitaire des systèmes thermiques industriels (IUSTI), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Matériaux et Mécanique des Composants (EDF R&D MMC), EDF R&D (EDF R&D), EDF (EDF)-EDF (EDF), Association EURATOM-CEA (CEA/DSM/DRFC), Département de Recherche sur la Fusion Contrôlée (DRFC), Laboratoire d'Interaction Laser Matière (LILM), Département de Physico-Chimie (DPC), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire de Physique des Plasmas (LPP), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École polytechnique (X)-Sorbonne Université-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut Jean Lamour (IJL), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Département de Physique Nucléaire (ex SPhN) (DPHN), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Ngee Ann Polytechnic, School of Engineering, Mechanical Engineering Division, ITER organization (ITER), CEA Cadarache, Centre de Thermique de Lyon (CETHIL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), CEA ISIS, Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Chimie de Clermont-Ferrand (ICCF), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Sciences et Techniques de la Ville - FR 2488 (IRSTV), Université de Nantes (UN)-École Centrale de Nantes (ECN)-EC. ARCHIT. NANTES-Université d'Angers (UA)-Université de La Rochelle (ULR)-Centre National de la Recherche Scientifique (CNRS), Eau et Environnement (IFSTTAR/GERS/EE), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR)-PRES Université Nantes Angers Le Mans (UNAM), Physique des interactions ioniques et moléculaires (PIIM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Centre of Molecular and Structural Biomedicine (CBME)/Institute of Biotechnology and Bioengineering (IBB), University of Algarve [Portugal], Laboratoire Lasers, Plasmas et Procédés photoniques (LP3), Centre d'Histoire 'Espaces et Cultures' (CHEC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP), École des hautes études en sciences sociales (EHESS), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), IFP Energies nouvelles (IFPEN), Matériaux, ingénierie et science [Villeurbanne] (MATEIS), Ecologie Systématique et Evolution (ESE), Centre National de la Recherche Scientifique (CNRS)-AgroParisTech-Université Paris-Sud - Paris 11 (UP11), Laboratoire d'Etude des Matériaux en Milieux Agressifs (LEMMA), Université de La Rochelle (ULR), CMCR des Massues, Croix rouge française, Laboratoire Procédés et Ingénierie en Mécanique et Matériaux (PIMM), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM), Laboratoire de Mécanique, Modélisation et Procédés Propres (M2P2), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), Réserve Naturelle Nationale Baie St-Brieuc, Réserves Naturelles de France-Réserves Naturelles de France, Géoazur (GEOAZUR 6526), Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Direction des Jardins botaniques et zoologiques, Muséum national d'Histoire naturelle (MNHN), Department of Information Technology (INTEC), Ghent University [Belgium] (UGENT), Dipartimento di Ingegneria dell'Ambiente e per lo Sviluppo Sostenibile (DIASS), Dipartimento Ingn Ambiente & Sviluppo Soste, Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2), Equipe Dynamique des Systemes Complexes, Université de Provence - Aix-Marseille 1, Technische Universität Braunschweig [Braunschweig], Laboratoire de physique des milieux ionisés et applications (LPMIA), Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon], Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Service de Chimie Physique (SCP), Laboratoire des Adaptations Physiologiques aux Activités Physiques (LAPHAP), Université de Poitiers, Institut d'Electronique du Solide et des Systèmes ( InESS ), Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche sur la Fusion par confinement Magnétique ( IRFM ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Science et Ingénierie des Matériaux et Procédés ( SIMaP ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -Institut National Polytechnique de Grenoble ( INPG ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Laboratoire de l'Accélérateur Linéaire ( LAL ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Physique Nucléaire et de Physique des Particules du CNRS ( IN2P3 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Météorologie Dynamique (UMR 8539) ( LMD ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -École polytechnique ( X ) -École des Ponts ParisTech ( ENPC ) -Centre National de la Recherche Scientifique ( CNRS ) -Département des Géosciences - ENS Paris, École normale supérieure - Paris ( ENS Paris ) -École normale supérieure - Paris ( ENS Paris ), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies ( FEMTO-ST ), Université de Technologie de Belfort-Montbeliard ( UTBM ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Institut universitaire des systèmes thermiques industriels ( IUSTI ), Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ), EDF - R&D Department MMC and MAI, EDF R&D ( EDF R&D ), EDF ( EDF ) -EDF ( EDF ), Association EURATOM-CEA ( CEA/DSM/DRFC ), Département de Recherche sur la Fusion Contrôlée ( DRFC ), Laboratoire d'Interaction Laser Matière ( LILM ), Département de Physico-Chimie ( DPC ), Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Laboratoire de Physique des Plasmas ( LPP ), Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Observatoire de Paris-École polytechnique ( X ) -Sorbonne Universités-PSL Research University ( PSL ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ), Institut Jean Lamour ( IJL ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Lorraine ( UL ), Département de Physique Nucléaire (ex SPhN) ( DPHN ), Institut de Recherches sur les lois Fondamentales de l'Univers ( IRFU ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, ITER [St. Paul-lez-Durance], ITER, Centre de Thermique de Lyon ( CETHIL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Electronique et des Technologies de l'Information ( CEA-LETI ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Grenoble Alpes [Saint Martin d'Hères], Institut de Chimie de Clermont-Ferrand ( ICCF ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Sigma CLERMONT ( Sigma CLERMONT ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Recherche en Sciences et Techniques de la Ville ( IRSTV ), Université d'Angers ( UA ) -Université de Nantes ( UN ) -École Centrale de Nantes ( ECN ) -Université de La Rochelle ( ULR ) -EC. ARCHIT. NANTES-Centre National de la Recherche Scientifique ( CNRS ), Eau et Environnement ( IFSTTAR/GERS/EE ), Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux ( IFSTTAR ) -PRES Université Nantes Angers Le Mans ( UNAM ), Physique des interactions ioniques et moléculaires ( PIIM ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Intégration des Systèmes et des Technologies ( LIST ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Institut des Sciences de l'Evolution de Montpellier ( ISEM ), Université de Montpellier ( UM ) -Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Lasers, Plasmas et Procédés photoniques ( LP3 ), Centre d'Histoire 'Espaces et Cultures' ( CHEC ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ), École des hautes études en sciences sociales ( EHESS ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Centre d'investigation clinique en cancérologie ( CI2C ), IFP Energies nouvelles ( IFPEN ), Matériaux, ingénierie et science [Villeurbanne] ( MATEIS ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ), Ecologie Systématique et Evolution ( ESE ), Université Paris-Sud - Paris 11 ( UP11 ) -AgroParisTech-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Etude des Matériaux en Milieux Agressifs ( LEMMA ), Université de La Rochelle ( ULR ), Institut des Sciences Chimiques de Rennes ( ISCR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Ecole Nationale Supérieure de Chimie de Rennes-Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Croix-rouge française, Procédés et Ingénierie en Mécanique et Matériaux [Paris] ( PIMM ), Centre National de la Recherche Scientifique ( CNRS ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Institut de Microélectronique, Electromagnétisme et Photonique - Laboratoire d'Hyperfréquences et Caractérisation ( IMEP-LAHC ), Centre National de la Recherche Scientifique ( CNRS ) -Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Institut National Polytechnique de Grenoble ( INPG ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -Université Grenoble Alpes ( UGA ), Laboratoire de Mécanique, Modélisation et Procédés Propres ( M2P2 ), Aix Marseille Université ( AMU ) -Ecole Centrale de Marseille ( ECM ) -Centre National de la Recherche Scientifique ( CNRS ), Géoazur ( GEOAZUR ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Observatoire de la Côte d'Azur, Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Réserve de la Haute Touche, Muséum National d'Histoire Naturelle ( MNHN ), Department of Information Technology ( INTEC ), Ghent University [Belgium] ( UGENT ), Dipartimento di Ingegneria dell'Ambiente e per lo Sviluppo Sostenibile ( DIASS ), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier ( ICGM ICMMM ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Physique des milieux ionisés et applications ( LPMIA ), Université Henri Poincaré - Nancy 1 ( UHP ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Bureau de Recherches Géologiques et Minières (BRGM) ( BRGM ), Catalyse par les métaux, Institut de Chimie des Milieux et Matériaux de Poitiers ( IC2MP ), Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ) -Université de Poitiers-Centre National de la Recherche Scientifique ( CNRS ), Service de Chimie Physique ( SCP ), Laboratoire des Adaptations Physiologiques aux Activités Physiques ( LAPHAP ), Institut de Recherche pour le Développement (IRD)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National Polytechnique de Grenoble (INPG)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Université d'Angers (UA)-Université de Nantes (UN)-École Centrale de Nantes (ECN)-Université de La Rochelle (ULR)-EC. ARCHIT. NANTES-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226, Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: Physics, [PHYS]Physics [physics], Nuclear and High Energy Physics, [ PHYS ] Physics [physics], Plasma parameters, Ripple, Plasma, Tore Supra, Collisionality, Condensed Matter Physics, 7. Clean energy, 01 natural sciences, 010305 fluids & plasmas, Computational physics, symbols.namesake, Nuclear magnetic resonance, Physics::Plasma Physics, 0103 physical sciences, symbols, Langmuir probe, Electron temperature, 010306 general physics, Power density
Abstract: International audience; Tore Supra routinely addresses the physics and technology of very long-duration plasma discharges, thus bringing precious information on critical issues of long pulse operation of ITER. A new ITER relevant lower hybrid current drive (LHCD) launcher has allowed coupling to the plasma a power level of 2.7 MW for 78 s, corresponding to a power density close to the design value foreseen for an ITER LHCD system. In accordance with the expectations, long distance (10 cm) power coupling has been obtained. Successive stationary states of the plasma current pro le have been controlled in real-time featuring (i) control of sawteeth with varying plasma parameters, (ii) obtaining and sustaining a `hot core' plasma regime, (iii) recovery from a voluntarily triggered deleterious magnetohydrodynamic regime. The scrape-off layer (SOL) parameters and power deposition have been documented during L-mode ramp-up phase, a crucial point for ITER before the X-point formation. Disruption mitigation studies have been conducted with massive gas injection, evidencing the difference between He and Ar and the possible role of the q = 2 surface in limiting the gas penetration. ICRF assisted wall conditioning in the presence of magnetic eld has been investigated, culminating in the demonstration that this conditioning scheme allows one to recover normal operation after disruptions. The effect of the magnetic eld ripple on the intrinsic plasma rotation has been studied, showing the competition between turbulent transport processes and ripple toroidal friction. During dedicated dimensionless experiments, the effect of varying the collisionality on turbulence wavenumber spectra has been documented, giving new insight into the turbulence mechanism. Turbulence measurements have also allowed quantitatively comparing experimental results with predictions by 5D gyrokinetic codes: numerical results simultaneously match the magnitude of effective heat diffusivity, rms values of density uctuations and wavenumber spectra. A clear correlation between electron temperature gradient and impurity transport in the very core of the plasma has been observed, strongly suggesting the existence of a threshold above which transport is dominated by turbulent electron modes. Dynamics of edge turbulent uctuations has been studied by correlating data from fast imaging cameras and Langmuir probes, yielding a coherent picture of transport processes involved in the SOL.
Published: 2011

2. Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia

Author: Ibrahim Yakoub-Agha, Noel Milpied, Gérard Socié, Didier Blaise, Anne Huynh, Sabine Furst, Jean El-Cheikh, R. Tabrizi, Philippe Moreau, Mohamad Mohty, Stephane Vigouroux, Thierry Guillaume, Florent Malard, Pierre Peterlin, Patrice Chevallier, Oumedaly Reman, Myriam Labopin, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de greffe de moelle osseuse [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, HAL UPMC, Gestionnaire, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Transplantation Conditioning, Graft vs Host Disease, Gastroenterology, 0302 clinical medicine, Adenine nucleotide, Antineoplastic Combined Chemotherapy Protocols, Clofarabine, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Adenine Nucleotides, Graft Survival, Cytarabine, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, Hematology, Articles, Middle Aged, Tissue Donors, 3. Good health, Leukemia, Myeloid, Acute, Treatment Outcome, 030220 oncology & carcinogenesis, Retreatment, Female, medicine.drug, Adult, medicine.medical_specialty, Cyclophosphamide, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 03 medical and health sciences, Young Adult, Internal medicine, Multicenter trial, medicine, Humans, Transplantation, Homologous, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Transplantation Chimera, business.industry, Survival Analysis, Surgery, Transplantation, Regimen, Drug Resistance, Neoplasm, Arabinonucleosides, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients' outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33-71) at 1 year and 38% (95% CI: 18-46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26-64) at 1 year and 29% (95% CI: 13-48) at 2 years. The cumulative incidence of non-relapse mortality was 8% (95% CI: 1-24) at 1 year and 12% (95% CI: 3-19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174.
Published: 2016
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3. Improvement of overall survival after allogeneic hematopoietic stem cell transplantation for children and adolescents: a three-decade experience of a single institution

Author: N Corradini, E Thebaud, Patrice Chevallier, Philippe Moreau, Rialland X, Francoise Mechinaud, N. Blin, Caroline Thomas, Xavier Cahu, Eolia Brissot, Noel-Jean Milpied, M. Strullu, Mohamad Mohty, J L Harousseau, Fanny Rialland, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), and CHU Pontchaillou [Rennes]
Subjects: Adult, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Hematopoietic stem cell transplantation, Single Center, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Cumulative incidence, Child, Survival rate, Retrospective Studies, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Infant, Retrospective cohort study, Hematology, Allografts, medicine.disease, Surgery, Survival Rate, Graft-versus-host disease, Child, Preschool, Hematologic Neoplasms, 030220 oncology & carcinogenesis, Stem cell, business, Follow-Up Studies, 030215 immunology
Abstract: International audience; Allogeneic stem cell transplantation (allo-SCT) has become an essential component of the treatment for a variety of diseases in pediatric patients. During the past decades, advances in the transplant technology, availability of hematopoietic stem cells and supportive care not only have resulted in improved outcomes, but also have expanded the transplant options. However, these features have been studied mainly in adult populations. This investigation analyzed changes in patient profile, transplantation, graft characteristics and outcome among 250 children and adolescent patients who received allo-SCT in a single center between 1983 and 2010. In the 2000–2010, compared with the 1983–1999 period, a significantly higher 5-year overall survival (64% versus 52%, P=0.03) was observed together with a significant decrease of non-relapse mortality (27% versus 9%, P=0.0002). The progression-free survival was comparable between the two periods (49% versus 57%; P=0.17). The 5-year cumulative incidence of relapse was 24% between 1983 and 1999, and 34% between 2000 and 2010 (P=0.08). Major advances in supportive care practice have been made over the past decade, resulting in a significant survival benefit for the pediatric population undergoing allo-SCT. However, post-transplant relapse remains the leading cause of failure of this therapeutic approach, and preventing relapse represents a major challenge today
Published: 2015

4. Effect of immune modulation in relapsed peripheral T-cell lymphomas after post-allogeneic stem cell transplantation: a study by the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

Author: J. Y. Cahn, Jean-Valère Malfuson, Charlotte Jubert, Didier Blaise, T. Lamy, Yves Beguin, M. Ouzegdouh, Reman Oumedaly, Felipe Suarez, M. Mohty, J.-O. Bay, Nathalie Contentin, Luc Mathieu Fornecker, Vincent Levy, Patrice Chevallier, E. Deconink, Aliénor Xhaard, Anne-Claire Mamez, J. H. Bourhis, Marie-Cécile Michallet, Veronique Leblond, Sébastien Maury, Gaelle Guillerm, Stephane Vigouroux, Nathalie Fegueux, Son Nguyen, N. Maillard, Ibrahim Yakoub-Agha, Pascal Turlure, Fanny Rialland, Norbert Ifrah, Claude-Eric Bulabois, M. Boubaya, Anne Huynh, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges], CHU Limoges, TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hématologie, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre d'investigation clinique en cancérologie (CI2C), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Hematopoietic stem cell transplantation, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Survival rate, Retrospective Studies, Transplantation, Chemotherapy, business.industry, Hazard ratio, Hematopoietic Stem Cell Transplantation, Lymphoma, T-Cell, Peripheral, Chemoradiotherapy, Hematology, Odds ratio, Middle Aged, Allografts, medicine.disease, 3. Good health, Surgery, Lymphoma, Survival Rate, Graft-versus-host disease, Lymphocyte Transfusion, 030220 oncology & carcinogenesis, business, Immunosuppressive Agents, Follow-Up Studies, 030215 immunology
Abstract: International audience; Peripheral T-cell lymphoma carries a poor prognosis. To document a possible graft-versus-lymphoma effect in this setting, we evaluated the impact of immunomodulation in 63 patients with peripheral T-cell lymphoma who relapsed after allogeneic transplant in 27 SFGM-TC centers. Relapse occurred after a median of 2.8 months. Patients were then treated with non-immunologic strategies (chemotherapy, radiotherapy) and/or immune modulation (donor lymphocyte infusions (DLI) and/or discontinuation of immunosuppressive therapy). Median overall survival (OS) after relapse was 6.1 months (DLI group: 23.6 months, non-DLI group: 3.6 months). Among the 14 patients who received DLI, 9 responded and 2 had stable disease. Among the remaining 49 patients, a complete response accompanied by extensive chronic GvHD was achieved in two patients after tapering of immunosuppressive drugs. Thirty patients received radio-chemotherapy, with an overall response rate of 50%. In multivariate analysis, chronic GvHD (odds ratio: 11.25 (2.68–48.21), P=0.0009) and skin relapse (odds ratio: 4.15 (1.04–16.50), P=0.043) were associated with a better response to treatment at relapse. In a time-dependent analysis, the only factor predictive of OS was the time from transplantation to relapse (hazards ratio: 0.33 (0.17–0.640), P=0.0009). This large series provides encouraging evidence of a true GvL effect in this disease
Published: 2015

5. Impact of body-surface area on patients' outcome in younger adults with acute myeloid leukemia

Author: Yosr Hicheri, Norbert Vey, Jean-Yves Cahn, Patrice Chevallier, Fabrice Larosa, Norbert Ifrah, Martin Carre, Emmanuel Gyan, Bouscary Didier, Chantal Himberlin, Bruno Lioure, Gaelle Guillerm, Christian Recher, Mario Ojeda-Uribe, Marie C. Béné, Marc Bernard, Caroline Bonmati, Arnaud Pigneux, Mathilde Hunault-Berger, Xavier Cahu, Jacques Delaunay, Service d'Hématologie Clinique, Centre hospitalier universitaire de Nantes (CHU Nantes), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Service des maladies du sang [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d'Hématologie [Nantes], Centre d'investigation clinique en cancérologie (CI2C), Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Service d'hématologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CIC - Tours, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, immunothérapie, chimie et cancer (GICC), UMR 7292 CNRS [2012-2017] (GICC UMR 7292 CNRS), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Département d'Oncologie et Hématologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire d'hématologie (Labo Hémato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Service d'hématologie clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, CHU Pontchaillou [Rennes], PRES Université Nantes Angers Le Mans (UNAM), Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], Université de Rennes (UR)-Hôpital Pontchaillou, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Tours-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Body Surface Area, medicine.medical_treatment, [SDV]Life Sciences [q-bio], acute myeloid leukemia, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Recurrence, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Multicenter Studies as Topic, Medicine, Body Weights and Measures, Young adult, Dose intensity, Survival analysis, Body surface area, Chemotherapy, business.industry, Remission Induction, Age Factors, Myeloid leukemia, Hematology, General Medicine, Survival Analysis, 3. Good health, Surgery, Leukemia, Myeloid, Acute, Treatment Outcome, Clinical Trials, Phase III as Topic, Postremission Therapy, dose reduction, Younger adults, 030220 oncology & carcinogenesis, Cytarabine, Female, body-surface area, business, 030215 immunology, medicine.drug
Abstract: International audience; OBJECTIVES: Anthracyclines and cytarabine are cornerstones for intensive chemotherapy in acute myeloid leukemia (AML). The goals of this study were to comprehensively assess deviations from theoretical doses and the impact of body-surface area (BSA) on patients' characteristics, physicians' strategy, dose adjustment, and clinical outcome. METHODS: The GOELAMS 2001 phase III trial included 823 AML patients below 60 years of age. In the course of treatment, anthropomorphic parameters and chemotherapy doses were prospectively registered. RESULTS: Very high BSA (≥2.15 m(2) ) was the factor most significantly associated with the physician's decision to reduce chemotherapy doses during induction and postremission therapy. Despite similar AML characteristics and therapeutic strategies, the very high BSA group exhibited a significantly worse survival (5-years OS of 27%) compared to the low (BSA≤1.5 m(2) ), intermediate (1.5 m(2)
Published: 2017

6. Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosome-positive ALL

Author: Magda Alexis, Norbert Ifrah, Laurent Sutton, Bruno Lioure, Patrice Chevallier, Jean-Michel Cayuela, Carlo Gambacorti Passerini, Valérie Robin, André Delannoy, José Fernandes, Françoise Huguet, Oumedaly Reman, Philippe Rousselot, Laure Morisset, Thibaut Leguay, Sandrine Hayette, Anne Banos, Caroline Bonmati, marie Magdelaine Coude, Philippe Agape, Renato Bassan, Xavier Thomas, Sylvie Glaisner, Celia Salanoubat, Josep M. Ribera, Dieter Hoelzer, Anne Bornand, Heike Pfeifer, Oliver G. Ottmann, Eric Jourdan, Marina Lafage-Pochitaloff, Marc Delord, Mathilde Hunault, Christian Berthou, Nicola Gökbuget, Hervé Dombret, Le Collège d'études mondiales/FMSH, Fondation Maison des sciences de l'homme (FMSH), Laboratoire Central d'Anatomie et de Cytologie Pathologiques [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], CHU Bordeaux [Bordeaux], Centre d'investigation clinique en cancérologie (CI2C), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional d'Orléans (CHRO), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Saint Jean de Perpignan, Hôpital d'Argenteuil, Hôpital de Bayonne, CH de la Côte Basque, Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, CHU Strasbourg, Hospices Civils de Lyon (HCL), Assistance Publique - Hôpitaux de Marseille (APHM), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche en Cancérologie de Lyon (CRCL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional d'Orléans (CHR), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Rousselot, P, Coudé, M, Gokbuget, N, Gambacorti Passerini, C, Hayette, S, Cayuela, J, Huguet, F, Leguay, T, Chevallier, P, Salanoubat, C, Bonmati, C, Alexis, M, Hunault, M, Glaisner, S, Agape, P, Berthou, C, Jourdan, E, Fernandes, J, Sutton, L, Banos, A, Reman, O, Lioure, B, Thomas, X, Ifrah, N, Lafage-Pochitaloff, M, Bornand, A, Morisset, L, Robin, V, Pfeifer, H, Delannoy, A, Ribera, J, Bassan, R, Delord, M, Hoelzer, D, Dombret, H, and Ottmann, O
Subjects: Male, Oncology, Survival, Clinical Trials and Observations, diagnosis, medicine.medical_treatment, Dasatinib, Fusion Proteins, bcr-abl, Hematopoietic stem cell transplantation, Comorbidity, Biochemistry, Polymerase Chain Reaction, Dexamethasone, 0302 clinical medicine, Maintenance therapy, Belgium, Germany, hemic and lymphatic diseases, Philadelphia Chromosome, genetics, Prospective Studies, Aged, 80 and over, Leukemia, Cytarabine, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Prognosis, 3. Good health, Italy, Vincristine, 030220 oncology & carcinogenesis, Medicine, Female, France, medicine.drug, Risk, Adult, medicine.medical_specialty, Patients, Immunology, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, medicine, Humans, Asparaginase, Dasatinib, TKI, Ph+ ALL, Protein Kinase Inhibitors, Molecular Biology, Aged, Chemotherapy, therapy, business.industry, Cell Biology, R1, Surgery, Transplantation, Imatinib mesylate, Methotrexate, Mutation, business, Laboratories, 030215 immunology, transplantation, Stem Cell Transplantation
Abstract: International audience; Prognosis of Philadelphia-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in the elderly has improved during the imatinib era. We investigated dasatinib, another potent tyrosine kinase inhibitor, in combination with low-intensity chemotherapy. Patients older than age 55 years were included in the European Working Group on Adult ALL (EWALL) study number 01 for Ph(+) ALL (EWALL-PH-01 international study) and were treated with dasatinib 140 mg/day (100 mg/day over 70 years) with intrathecal chemotherapy, vincristine, and dexamethasone during induction. Patients in complete remission continued consolidation with dasatinib, sequentially with cytarabine, asparaginase, and methotrexate for 6 months. Maintenance therapy was dasatinib and vincristine/dexamethasone reinductions for 18 months followed by dasatinib until relapse or death. Seventy-one patients with a median age of 69 years were enrolled; 77% had a high comorbidity score. Complete remission rate was 96% and 65% of patients achieved a 3-log reduction in BCR-ABL1 transcript levels during consolidation. Only 7 patients underwent allogeneic hematopoietic stem cell transplantation. At 5 years, overall survival was 36% and up to 45% taking into account deaths unrelated to disease or treatment as competitors. Thirty-six patients relapsed, 24 were tested for mutation by Sanger sequencing, and 75% were T315I-positive. BCR-ABL1(T315I) was tested by allele-specific oligonucleotide reverse transcription-quantitative polymerase chain reaction in 43 patients and detection was associated with short-term relapses. Ten patients (23%) were positive before any therapy and 8 relapsed, all with this mutation. In conclusion, dasatinib combined with low-intensity chemotherapy was well-tolerated and gave long-term survival in 36% of elderly patients with Ph(+) ALL. Monitoring of BCR-ABL1(T315I) from diagnosis identified patients with at high risk of early relapse and may help to personalize therapy
Published: 2016

7. Single- vs double-unit cord blood transplantation for children and young adults with acute leukemia or myelodysplastic syndrome

Author: Mohamad Mohty, Fanny Rialland, Patrick Lutz, Karine Baumstarck, Anderson Loundou, Sophie Esmiol, Charlotte Jubert, Claire Galambrun, Ibrahim Yakoub-Agha, Mauricette Michallet, Didier Blaise, Cécile Pochon, Anne Sirvent, Jean-Hugues Dalle, Gérard Michel, Claire Oudin, Bénédicte Bruno, Virginie Gandemer, Aude Marie-Cardine, Vanderson Rocha, Mylène Seux, Noel Milpied, Cecile Renard, Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut Gustave Roussy (IGR), Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de pédiatrie, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Service d’Hématologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service d'Hématologie Clinique [Nantes], Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Chimie Provence (LCP), Université de Provence - Aix-Marseille 1-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Churchill Hospital, Churchill Hospital Oxford Centre for Haematology, Eurocord, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), France Monacord, Centre Scientifique de Monaco (CSM), Hôpital Robert Debré Paris, Hôpital Robert Debré, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and Centre National de la Recherche Scientifique (CNRS)-Université de Provence - Aix-Marseille 1-Institut de Chimie du CNRS (INC)
Subjects: Male, Transplantation Conditioning, [SHS.PSY]Humanities and Social Sciences/Psychology, Graft vs Host Disease, Biochemistry, Gastroenterology, 0302 clinical medicine, Child, Acute leukemia, Leukemia, Hematology, Total body irradiation, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Quality, 3. Good health, Survival Rate, surgical procedures, operative, 030220 oncology & carcinogenesis, Child, Preschool, Acute Disease, Female, Cord Blood Stem Cell Transplantation, Whole-Body Irradiation, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Immunology, Disease-Free Survival, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Humans, Survival rate, Antilymphocyte Serum, business.industry, Myelodysplastic syndromes, Cell Biology, medicine.disease, Surgery, Transplantation, [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Myelodysplastic Syndromes, Chronic Disease, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Busulfan, 030215 immunology
Abstract: Transplantation of 2 unrelated cord blood (UCB) units instead of 1 has a been proposed to increase the cell dose. We report a prospective a randomized study, designed to compare single-vs double-UCB a transplantation in children and young adults with acute leukemia in a remission or myelodysplasia. Eligible patients had at least two 4-6 a HLA-identical UCBs with >3x10(7) nucleated cells/kg for the first and a >1.5x10(7) for the second. The primary end point was the 2-year a cumulative incidence of transplantation strategy failure, a composite a end point including transplant-related mortality (TRM), engraftment a failure, and autologous recovery. Randomized patients who did not a proceed to transplantation due to refractory disease were considered a transplantation failures. A total of 151 patients were randomized and a included in the intent-to-treat analysis; 137 were transplanted. a Double-UCB transplantation did not decrease transplantation strategy a failure (23.4% 6 4.9% vs 14.9% +/- 4.2%). Two-year posttransplant a survival, disease-free survival, and TRM were 68.8% +/- 6.0%, 67.6% a +/- 6.0%, and 5.9% +/- 2.9% after single-unit transplantation a compared with 74.8% +/- 5.5%, 68.1% +/- 6.0%, and 11.6% +/- 3.9% a after double-unit transplantation. The final relapse risk did not a significantly differ, but relapses were delayed after double-unit a transplantation. Overall incidences of graft-versus-host disease (GVHD) a were similar, but chronic GVHD was more frequently extensive after a double-UCB transplantation (31.9% +/- 5.7% vs 14.7% +/- 4.3%, a P=.02). In an exploratory subgroup analysis, we found a significantly a lower relapse risk after double-unit transplantation in patients a receiving total body irradiation without antithymocyte globulin (ATG), a whereas the relapse risk was similar in the group treated with busulfan, a cyclophosphamide, and ATG. Single-UCB transplantation with adequate cell a dose remains the standard of care and leads to low TRM. Double-unit a transplantation should be reserved for patients who lack such units. a This trial was registered at www. clinicaltrials. gov as #NCT01067300.
Published: 2016

8. Keep in mind quality of life: outcome of a 10-year series of post-transplant early relapses in childhood acute lymphoblastic leukemia A report from the GOCE, the Grand Ouest oncology study group for children in France

Author: Haro, S., Tavenard, A., Rialland, F., Taque, S., Guillerm, G., Blouin, P., Esvan, M., Pellier, I., Gandemer, V, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), CHRU Brest - Service d'Hématologie (CHU-Brest-Hemato), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Jonchère, Laurent, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Early, [SDV.CAN] Life Sciences [q-bio]/Cancer, Hematopoietic stem cell transplantation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Relapse, Children, Lymphoblastic leukemia
Abstract: International audience; Relapses of acute lymphoblastic leukemia (ALL) early after hematopoietic stem cell transplantations in children are uncommon but associated with a very poor prognosis. Whereas there are no current recommendations for the management of these relapses, the children's quality of life is an important issue. We studied the outcomes, including 1-year overall survival, complete remission, and quality of life, of 19 children with ALL who relapsed within the first year after their transplantation treated in the 5 participating centers between 2000 and 2011 Patients were distributed as follows: supportive care only (group A), outpatient treatment (mainly steroid and vincristine, group B), or intensive inpatient treatment (group C). There were no significant differences in 1-year overall survival (31.5% for the entire cohort) or remission rate for time between transplantation and relapse (< 6 months or 6 to 12 months), transplantation or disease characteristics, or treatment group. However, time spent in hospital (for treatment and complications) significantly differed between treatment groups B and C (20.8% ± 13.0 versus 59.1% ± 32.9, respectively; P < .05). No differences in organ toxicities, school attendance, or Lansky scores were found between treatment groups. Our sample size-limited data indicate, in a prepersonalized medicine era, that children treated with steroid and vincristine have the same prognosis as those treated with intensive therapy, but they may benefit from improved quality of life. Nevertheless, new therapeutic strategies are required and future prospective trials would help to establish recommendations.
Published: 2016

9. Prevention of Venous Thrombotic Events in Adult Patients with Acute Lymphoblastic Leukemia Treated in a Pediatric-Inspired Protocol - a Graall Study

Author: Emmanuelle Tavernier, Denis Caillot, Yves Chalandon, Sylvain Chantepie, Françoise Huguet, Thomas Pabst, Norbert Ifrah, Corentin Orvain, Nicolas Boissel, Hervé Dombret, Patrice Chevallier, Marie Balsat, Mathilde Hunault-Berger, Véronique Lhéritier, Jamile Frayfer, Victoria Cacheux, Noémie de Gunzburg, Jean-Pierre Marolleau, Caroline Bonmati, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'hématologie, PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service des maladies du sang, Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Institut de Cancérologie de la Loire Lucien Neuwirth, Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CHU Amiens-Picardie, Inselspital Bern, Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Centre Hospitalier de Versailles André Mignot (CHV), CHU Clermont-Ferrand, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpitaux Universitaires de Genève (HUG), Centre Hospitalier de Meaux, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), PRES Université Nantes Angers Le Mans (UNAM), and DESSAIVRE, Louise
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Immunology, Biochemistry, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, 030212 general & internal medicine, business.industry, Cell Biology, Hematology, Odds ratio, medicine.disease, Thrombosis, Surgery, Discontinuation, Pulmonary embolism, Transplantation, [SDV] Life Sciences [q-bio], Venous thrombosis, Platelet transfusion, 030220 oncology & carcinogenesis, Fresh frozen plasma, business
Abstract: Background: Patients undergoing treatment for acute lymphoblastic leukemia (ALL) are at risk for thrombosis, in part due to the use of L-asparaginase (L-ASP) and subsequent antithrombine (AT) deficiency. Previous reports showed that patients with venous thrombotic events (VTE) have a lower event-free survival that may be due to early discontinuation of L-ASP. It has been suggested that AT replacement could decrease the rate of thrombosis and prevent L-ASP discontinuation. We report herein the results of the prophylactic replacement strategy in the pediatric-inspired prospective GRAALL-2005 study. Methods: All patients received a 5-drug induction therapy with 8 native E. Coli-ASP intravenous injections (6,000 UI/m2/injection). Patients in complete remission (CR) received two consolidation courses each containing two L-ASP intravenous injections (10000 UI/m2/injection). All patients in persistent CR for whom allogeneic stem cell transplantation was not indicated in first CR received a late intensification with the same drugs as in the induction course, followed by the repetition of one consolidation course. Platelet transfusion support was recommended for platelets below 20 x 109/L, fresh frozen plasma (FFP) or fibrinogen concentrates were recommended if fibrinogen levels fell below 0.5 g/L, and AT concentrate substitution therapy was recommended in order to maintain AT levels above 60%. Prophylactic heparin was recommended during induction and late intensification. All cases of VTE were identified prospectively by clinical signs and confirmed by radiological imaging based on institutional guidelines. Results: Between 2006 and 2014, 787 adult patients with newly diagnosed Philadelphia-negative ALL were included. The incidence rate of VTE was 14.4% (113 VTEs in 110 patients). VTEs included 72 (64%) deep vein thromboses (DVT), with one third in the lower limb and two thirds in the upper limb, 32 (28%) cerebral venous thrombosis (CVT), and 13 (12%) pulmonary embolism (PE). No disease characteristic was associated with a higher risk of thrombosis. Patients with DVT and/or PE were older (median age of 40 versus 38 for those with CVT versus 35 for those without VTE, p=0.04), had a higher BMI (median BMI of 26 versus 23 for those with CVT and 24 for those without VTE, p=0.01), and had a higher platelet count at diagnosis (median platelet count of 100 G/l versus 84 G/l for those with CVT versus 68 G/l for those without VTE, p=0.06) whereas patients with CVT had higher hemoglobin levels (median hemoglobin level of 11.7 g/dl versus 10.1 g/dl for those with DVT/PE versus 10.2 g/dl for those without VTE, p=0.03). Sixty-seven percent of VTEs occurred during induction therapy. Other VTEs occurred as follows: 17 (15%) during consolidation phase 1 (688 patients), 4 (4%) during consolidation phase 2 (537 patients), 9 (8%) during late intensification (356 patients), and 7 (6%) in 335 during consolidation phase 3 (335 patients). The type of thrombosis was different according to treatment phase as most CVT occurred during induction therapy (29 versus 3 CVTs during subsequent phases of treatment, p=0.003). During induction therapy, patients with VTE were more likely to have received heparin prophylaxis (82% versus 60% for those without VTE, odds ratio (OR) 1.8, p=0.06) and fibrinogen prophylaxis (14% versus 8% for those without VTE, OR 2, p=0.05) whereas they received less AT prophylaxis (82% versus 88% for those without VTE, OR 0.5, p=0.05). Patients with VTE received less L-ASP infusions during induction therapy (median number of 7 versus 8 injections for those without VTE, p Conclusion: In ALL patients receiving L-ASP therapy, appropriate AT prophylaxis was associated with less VTE and should be used extensively. Maintaining higher AT levels in patients at increased risk for VTE should be evaluated. L-ASP can be reintroduced in patients who experienced VTE during induction as none had thrombotic recurrence. Fibrinogen concentrates may increase the risk of thrombosis and should be restricted to patients with hemorrhage. Disclosures Dombret: Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau.
Published: 2016

10. Winning Cord Blood Unit Characteristics Impacting on Outcomes after Double Umbilical Cord Blood Transplantation in Adults with Acute Leukemia: a Collaborative Study of Eurocord and the Acute Leukemia Working Party of EBMT

Author: Giannotti, F., Ruggeri, A., Labopin, M., Cornelissen, J., Michallet, M., Karakasis, D., Deconinck, E., Rohrlich, P. -S, Socie, G., Didier Blaise, Petersen, E., Feugier, P., Sengeloev, H., Lamy, T., Russell, N. H., Vigouroux, S., Craddock, C. F., Kenzey, C., Mohty, M., Gluckman, E., Nagler, A., Rocha, V., Jonchère, Laurent, Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hospices Civils de Lyon (HCL), Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience; Conference: 42nd Annual Meeting of the European-Society-for-Blood-and-Marrow-Transplantation, Valencia, SPAIN, APR 03-06, 2016
Published: 2016

11. Escalated lymphodepletion followed by donor lymphocyte infusion can induce a graft-versus-host response without overwhelming toxicity

Author: Philippe Moreau, Patrice Chevallier, Fanny Rialland, Thomas Gastinne, Thierry Guillaume, Aline Clavert, Sameh Ayari, Béatrice Mahé, V. Dubruille, S. Le Gouill, Jacques Delaunay, M. Mohty, Béatrice Gaugler, N. Blin, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Saas, Philippe
Subjects: Adult, Male, Time Factors, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, medicine.medical_treatment, Graft vs Host Disease, Pilot Projects, Hematopoietic stem cell transplantation, T-Lymphocytes, Regulatory, Lymphocyte Depletion, Donor lymphocyte infusion, 03 medical and health sciences, 0302 clinical medicine, Immune system, Living Donors, medicine, Humans, Transplantation, Homologous, Prospective Studies, Aged, Transplantation, Chemotherapy, business.industry, Incidence, Interleukin-7, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, 3. Good health, Fludarabine, Cytokine, Hematologic Neoplasms, Lymphocyte Transfusion, 030220 oncology & carcinogenesis, Immunology, Toxicity, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Interleukin-5, business, 030215 immunology, medicine.drug
Abstract: International audience; Treatment of relapse of hematological malignancies following allogeneic hematopoietic SCT (allo-HSCT) remains very challenging and relies usually on the readministration of chemotherapy combined with donor lymphocyte infusion (DLI). To enhance DLI effectiveness, lymphodepletion (LD) with fludarabine (Flu) and/or CY before the injection of lymphocytes is an attractive modality to modify the immune environment, leading possibly to suppression of regulatory T cells (T(reg)) and exposing the patient to cytokine activation. However, LD before DLI may lead to induction of deleterious GVHD. To avoid inducing overwhelming toxicity, we proceeded by escalating doses of both LD and DLI. Eighteen patients with various non-CML hematological malignancies who relapsed following allo-HSCT were treated with chemotherapy and LD-DLI or LD-DLI upfront. T-cell subpopulation and DC levels as well as cytokine plasma levels (IL-7, IL-15) were measured before and following LD-DLI. Cumulative incidence of acute grade II-IV GVHD was 29.4% similar to that reported in patients receiving DLI without LD. In addition, Flu alone with low dose of DLI was not associated with severe GHVD. CY/Flu at the respective doses of 600 mg/m(2) on day 1 and Flu 25 mg/m(2)/day on days 1-3 did not result in a marked decrease of T(reg) cells, nor in endogenous IL-7 and IL-15 production. However, a peripheral expansion of DCs was observed. These findings suggest that the escalated dose procedure appears safe and prevent overwhelming toxicity. A dose-limiting toxicity has not yet been reached.Bone Marrow Transplantation advance online publication, 28 November 2011; doi:10.1038/bmt.2011.231.
Published: 2011

12. Reduced-toxicity conditioning prior to allogeneic stem cell transplantation improves outcome in patients with myeloid malignancies

Author: Christian Chabannon, Benjamin Esterni, Patrice Chevallier, Catherine Faucher, Luca Castagna, Raynier Devillier, Mohamad Mohty, Angela Granata, Sabine Furst, Jean El Cheikh, Jacques Delaunay, Claire Oudin, Thierry Guillaume, Norbert Vey, Didier Blaise, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Aix Marseille Université (AMU), Service d'Hématologie Clinique [Nantes], Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Istituto Clinico Humanitas [Milan] (IRCCS Milan), Humanitas University [Milan] (Hunimed), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique en cancérologie (CI2C), Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), HAL UPMC, Gestionnaire, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)
Subjects: Adult, Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, medicine.medical_specialty, Transplantation Conditioning, Adolescent, medicine.medical_treatment, Karyotype, Graft vs Host Disease, Comorbidity, Hematopoietic stem cell transplantation, Gastroenterology, Young Adult, Recurrence, Internal medicine, medicine, Humans, Transplantation, Homologous, Cumulative incidence, Survival rate, Aged, Neoplasm Staging, business.industry, Myelodysplastic syndromes, Hematopoietic Stem Cell Transplantation, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Articles, Hematology, Middle Aged, medicine.disease, 3. Good health, Surgery, Fludarabine, Transplantation, Leukemia, Myeloid, Acute, Treatment Outcome, Myelodysplastic Syndromes, Toxicity, Female, business, medicine.drug
Abstract: International audience; The introduction of reduced intensity/toxicity conditioning regimens has allowed allogeneic hematopoietic cell transplantation to be performed in patients who were previously considered too old or otherwise unfit. Although it led to a reduction in non-relapse mortality, disease control remains a major challenge. We studied the outcome of 165 patients with acute myeloid leukemia (n=124) or myelodysplastic syndrome (n=41) transplanted after conditioning with fludarabine (30 mg/m2/day for 5 days), intravenous busulfan (either 260 mg/m2: reduced intensity conditioning, or 390–520 mg/m2: reduced toxicity conditioning), and rabbit anti-thymoglobulin (2.5 mg/kg/day for 2 days). The median age of the patients at transplantation was 56.8 years. The 2-year relapse incidence was 29% (23% versus 39% for patients transplanted in first complete remission and those transplanted beyond first complete remission, respectively; P=0.008). The 2-year progression-free survival rate was 57% (95% CI: 49.9–65). It was higher in the groups with favorable or intermediate cytogenetics than in the group with unfavorable cytogenetics (72.7%, 60.5%, and 45.7%, respectively; P=0.03). The cumulative incidence of grades 2–4 and 3–4 acute graft-versus-host disease at day 100 was 19.3% and 7.9%, respectively. The cumulative incidence of chronic graft-versus-host disease at 1 year was 21.6% (severe forms: 7.8%). Non-relapse mortality at 1 year reached 11%. The 2-year overall survival rate was 61.8% (95% CI: 54.8–69.7). Unfavorable karyotype and disease status beyond first complete remission were associated with a poorer survival. This well-tolerated conditioning platform can lead to long-term disease control and offers possibilities of modulation according to disease stage or further development.
Published: 2014

13. Long Term Follow-up of Hematopoietic Stem Cell Transplantation (HSCT) for Primary Plasma Cell Leukemia (pPCL): Final Results of a Prospective Study of IFM Group

Author: Jean Gabriel Fuzibet, Annie Brion, Bertrand Arnulf, Lotfi Benboubker, Momar Diouf, Karim Belhadj, Xavier Leleu, Stephane Minvielle, Sylvie Cailleres, Jean Pierre Marolleau, Cyrille Hulin, Carine Chaleteix, Luc-Matthieu Fornecker, Bruno Royer, Murielle Roussel, Sylvain Choquet, Lionel Karlin, Marc Wetterwald, Laurent Garderet, Philippe Moreau, Herve Avet Loiseau, Charles Dauriac, Mourad Tiab, Sabine Brechignac, Margaret Macro, Thierry Facon, Laurent Frenzel, Marie Lorraine Chretien, CHU Amiens-Picardie, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Général [Aix en Provence], Centre Hospitalier Régional Universitaire de Besançon - CHRU Besançon, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Intercommunal de Créteil (CHIC), Service d'Hématologie Clinique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Général de Dunkerque, CHU Clermont-Ferrand, Hôpital Général de La Roche sur Yon, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Necker - Enfants Malades [AP-HP], Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital L'Archet [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Pontchaillou [Rennes], CHU Strasbourg, Hôpital Universitaire de Tours, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Hématologie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Pôle Institut Universitaire du Cancer - Oncopole [CHU Toulouse] (Pôle IUC - Oncopole), CHU Toulouse [Toulouse]-Oncopole de Toulouse, Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), and UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)
Subjects: medicine.medical_specialty, Long term follow up, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Immunology, Hematopoietic stem cell transplantation, Peripheral Blood Stem Cells, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Prospective cohort study, Lenalidomide, Plasma cell leukemia, business.industry, Cell Biology, Hematology, medicine.disease, Surgery, Transplantation, 030220 oncology & carcinogenesis, Chronic gvhd, business, 030215 immunology, medicine.drug
Abstract: Introduction: pPCLis a rare form of multiple myeloma (MM) with very poor outcome. Current strategies including novel agents and transplantation (auto or allo-HSCT) may improve survival but the prognosis remains poor. The IFM recently published results from a prospective study incorporating tandem auto/allo-HSCT or auto/auto and maintenance after alternate induction (doxorubicin-bortezomib-cyclophosphamide and dexamethasone: PAD/VCD) in 40 pPCL patients. We report here outcomes of patients who effectively underwent second transplant (auto or allo) with long-term follow-up. Methods: 24 over 40 patients actually received second transplant:allo-HSCT (as per protocol) forpatients< 60 years-old with a donor, second auto-HSCT for others. At time of second transplant, response rates were: sCR (n=1), CR (n=8), VGPR (n=10), PR (n=5) (cf table). 7 patients received high-dose melphalan (HDM)/auto-HSCT followed by maintenance consisting in Bortezomib-Lenalidomide-Dex (VRD) every 3 months and Lenalidomideduring other months for 1 year. 17 others patients underwent allo-HSCT: syngenic(n=1) or reduced intensity conditioning (RIC)-Allo (n=16). The conditioning regimens for allo were: fludarabin-busulfan-antithymoglobulin(n=13), fludarabin-melphalan(n=1), bortezomib-fludarabin-melphalan(n=2) and HDM for syngenic(n=1). They were grafted with peripheral blood stem cells except 1 who received bone marrow and 1 cord blood unit, from related (n=9) or HLA-matched unrelated donors (n=8): median infused CD34 cells was 6.8 106/kg [3-8.5]; all pts receivedciclosporine+/-methotrexate as GvHD prophylaxis. Results: As of June 2016, median follow-up from diagnosis was44.7months[41.0;57.6], 10 patientswerestillalive.MedianPFS for allo and auto ptswas18.5months[17.8;-] and 50.1months[25.6;-]respectively ;medianOSwas39.3months[26.6;-] and notreached,respectively.Inlandmarkanalysisfromdate of second transplant, PFSwas12.2 months [8.1 ;-] for allo pts and 40.0months[17.7;-] for auto pts (p=0.085); OSwas30.0months[28.6;-] and notreached,respectively(p=0.026). 2 allo ptsdiedbefored100evaluation ; 18 patients (75%)werein VGPR orbetter : sCR=2, RC=8, VGPR=8 ; 4 patients (17%)werein PR. For allo-HSCT : 6patients developed acute GvHD which responded to steroid in 5 cases and 1 was steroid-resistant and responded secondary to anti-IL2Rα antibody;5 patients experienced chronic GVHD (mild [n=4], extensive [n=1]).3 patients received 3 months after allo as immunomodulation, donor lymphocyte infusions plusLenalidomide-Cyclophosphamide-Fludarabin(n=1), Bortezomib (n=1) and Lenalidomide (n=1): one patient in PR achieved CR and the two others in VGPR maintained their response.Day 100 treatment-related mortality was 12%: 2 patients had Epstein-Barr virus reactivation, with 1 experiencing neuromeningeal relapse of pPCL and 1 concomitant disseminated toxoplasmosis. For auto-HSCT: as per protocol, 6 received a second HDM/auto, and 1 declined. Consolidation with VRD/Len was initiated in these 7 patients: 4 receiving the planned 1 year of treatment and 3 discontinuing after 4, 8, and 10 months as a result of prolonged cytopenia. Conclusion: This is the first large prospective trial for pPCL patients including tandem auto/auto-HSCT or tandem auto/RIC-allo after induction including proteasome inhibitor. This approach is feasible, and induces high response rate but relapses remain frequent especially after RIC-allo. Tandem auto/auto plus maintenance may be superior to tandem auto/alloregarding PFS and OS. In a future trial, we will investigate tandem auto/auto after induction incorporating novel proteasome inhibitor, anti-CD38 monoclonal antibody and Lenalidomide, and followed by consolidation and prolonged maintenance. Table: characteristics of Patients Table: characteristics of Patients Figure PFS / OS Figure. PFS / OS Disclosures Roussel: amgen: Consultancy; Janssen: Consultancy; celgene: Consultancy. Karlin:janssen-cilag: Consultancy, Honoraria; amgen: Consultancy, Honoraria; celgene: Consultancy, Honoraria; Bristol: Consultancy; takeda: Consultancy. Hulin:Janssen: Honoraria; Bristol: Honoraria; Amgen: Honoraria; takeda: Honoraria; celgene: Honoraria. Macro:sanofi: Consultancy; Novartis: Honoraria; Bristol: Consultancy; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgen: Consultancy, Honoraria. Belhadj:janssen: Consultancy; novartis: Consultancy. Chaleteix:Amgen: Honoraria; Janssen: Honoraria. Leleu:TEVA: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria. Garderet:Takeda: Consultancy; Amgen: Consultancy; BMS: Consultancy, Honoraria; Novartis: Consultancy. Choquet:Janssen: Consultancy; Celgene: Consultancy. Fornecker:Roche: Consultancy; Takeda: Consultancy; Gilead: Consultancy; Mundipharma: Speakers Bureau. Facon:Novartis: Consultancy; Amgen: Consultancy, Speakers Bureau; Millenium/Takeda: Consultancy; Celgene: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Bristol: Consultancy; Karyopharm: Consultancy. Moreau:Bristol-Myers Squibb: Honoraria; Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Celgene: Honoraria.
Published: 2016

14. The c.273+11dup genetic change in the WAS gene is a functionally neutral polymorphism

Author: Laurence, Jeanson-Leh, Sabine, Charrier, Alexis, Proust, Chrystele, Bilhou-Nabéra, Rémi, Favier, Caroline, Deswarte, Pierre, Bordigoni, Anne, Galy, Jean, Delaunay, Immunologie moléculaire et biothérapies innovantes (IMBI), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Laboratoire Environnements Sédimentaires (LES), Géosciences Marines (GM), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Institut Parisien de Chimie Moléculaire (IPCM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Biomécanique et génie biomédical (BIM), Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), École pratique des hautes études (EPHE), Laboratoire Environnements Sédimentaires - Géosciences Marines (GM/LES), and Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)
Subjects: Polymorphism, Genetic, Genetic, Base Sequence, Gene Duplication, [SDV]Life Sciences [q-bio], Mutation, Humans, Wiskott-Aldrich Syndrome Protein/*genetics, Wiskott-Aldrich Syndrome Protein, Polymorphism, Introns, DNA Primers
Abstract: International audience; Several pediatric patients showing symptoms consistent with the Wiskott-Aldrich syndrome (WAS) were referred to us and turned out to display the c.273+11dup change in the WAS gene. It consisted of the insertion of one C in an unusual tract of 7C near the intron 2 donor splicing site of the WAS gene. In the patients, non-synonymous WAS mutations were found twice only and one mutation was elucidated in RUNX1. In the absence of a non-synonymous mutation in the WAS gene, the c.273+11dup change affected neither the levels nor the sequence of WAS mRNA. In the presence of a non-synonymous WAS mutation, the c.273+11dup alteration failed to worsen the expected phenotype. Minor splicing abnormalities concerning exon 10 were observed both in WAS patients, and in healthy individuals carrying or not carrying the c.273+11dup. The c.273+11dup change was encountered four times in 107 normal male and female controls (172 alleles tested: 2.3%), and eight times in a series of 248 male patients (248 alleles tested: 3.2%). We conclude that the presence of the additional C in the WAS gene is a functionally neutral polymorphism.
Published: 2011

15. Prospective randomized study of doxorubicin-eluting-bead embolization in the treatment of hepatocellular carcinoma: results of the PRECISION V study

Author: Watkinson, A., Avajon, Y., Gruenberger, T., Pomoni, M., Schuchmann, M., Mueller, C., Lencioni, R., Lammer, J., Langenberger, H., Schoder, M., Funovics, M., Loewe, C., Moyses, J., Grunberger, T., Waldenberger, P., Chemelli, A., Graziadei, I., Vogl, T., Khan, V., Hammerstingl, R., Lee, C., Eichler, K., Pitton, M., Klockner, R., Duber, C., Otto, G., Worns, M. A., Greten, T., Kirchhoff, T., Rosenthal, H., Lotz, J., Huppert, P., Wietholtz, H., Limmer, A., Pilleul, F., Ficarelli, S., Mennesson, N., Rauscher, N., Dumortier, J., Guillaud, O., Vilgrain, V., Sibert, A., Chevallier, P., Novellas, S., Tran, A., Ouzan, D., Gugenheim, J., Sergent, G., Otal, P., Joffre, F., Auriol, J., Peron, J. M., Benhamou, Y., Ratzui, V., Clluzel, P., Baere, T., Deschamps, F., Roo, P., Ajavon, Y., Awad, S., Bellin, M. F., Samuel, D., Castaing, D., Adam, R., Vallee, J. C., Saliba, F., Azoulay, D., Denys, A., Triller, J., Kickuth, R., Terraz, S., Becker, C. D., Majno, P., Spahr, L., Pfammatter, T., Weishaupt, D., Muellhaupt, B., Malagari, K., Maria, P., Kelekis, D., Kelekis, N., Kelekis, A., Emmanouil, E., Pisa University Hospital and School of Medicine, Department of Chemistry, North Carolina Raleigh, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'hépatologie, Hospices Civils de Lyon (HCL), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'investigation clinique en cancérologie (CI2C), Animal et gestion intégrée des risques (UPR AGIRs), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Institut Arnault Tzanck, Service de Chirurgie Digestive et Transplantation Hépatique, Hôpital Archet II, Service de Radiologie [Rangueil / Larrey], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagerie thérapeutique (radiologie interventionnelle), Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), ETH Hoenggerberg, Institute of Geophysics, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hépato-Biliaire, Stadtspital Triemli Zürich, Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie Digestive / Centre de Transplantation Hépatique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), and Ratiney, Helene
Subjects: [SDV.IB.IMA] Life Sciences [q-bio]/Bioengineering/Imaging, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2010

16. Fungal Prophylaxis with a Gastro-Resistant Posaconazole Tablet for Patients with Hematological Malignancies in the POSANANTES Study.

Author: Peterlin P, Chauvin C, Le Gouill S, Pere M, Dalichampt M, Guillaume T, Garnier A, Paré M, Le Bourgeois A, Moreau P, Chevallier P, Deslandes G, and Gastinne T
Subjects: Adult, Aged, Antibiotic Prophylaxis methods, Female, Graft vs Host Disease microbiology, Hematologic Neoplasms microbiology, Hematopoietic Stem Cell Transplantation methods, Humans, Invasive Fungal Infections drug therapy, Invasive Fungal Infections microbiology, Male, Middle Aged, Multivariate Analysis, Prospective Studies, Young Adult, Antifungal Agents therapeutic use, Fungi drug effects, Hematologic Neoplasms drug therapy, Stomach physiology, Tablets therapeutic use, Triazoles therapeutic use
Abstract: Posaconazole is an antifungal drug used in both prophylaxis and treatment of invasive fungal infections. Its oral formulation requires therapeutic drug monitoring. To overcome gastric acidity, a gastro-resistant posaconazole tablet has recently been developed. POSANANTES was a prospective noninterventional study that aimed to monitor plasma concentration trough level ( C min ) of posaconazole tablets used prophylactically in patients with hematological malignancies. Fifty patients were included. Group A ( n = 31) included patients receiving induction chemotherapy for myeloid malignancies, and group B ( n = 19) included patients treated for graft-versus-host disease after allogeneic hematopoietic stem cells transplantation. In multivariate analysis, female sex, group B assignment, and evaluation of C min at day 8 (versus any other day planned by the analysis) were associated with a higher C min , while diarrhea was associated with a lower C min ( P < 0.05). Thirty-four percent ( n = 17) of all included patients had to prematurely stop treatment, mainly in group A. In conclusion, this real-life prospective study showed good absorption of posaconazole tablets used for prophylaxis in patients with hematological malignancies, even though this strategy was somewhat limited due to the high number of patients in group A who had to stop their treatment in an untimely fashion., (Copyright © 2018 American Society for Microbiology.)
Published: 2018
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17. Subcutaneous rituximab given to patients for other indications than CD20+ B-cell lymphoma: A monocentric study of 20 cases.

Author: Peterlin P, Guillaume T, Garnier A, Le Bourgeois A, Mahé B, Dubruille V, Blin N, Gallas P, Touzeau C, Gastinne T, Lok A, Thomare P, Chauvin C, Le Gouill S, Moreau P, and Chevallier P
Published: 2018
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18. Prevalence of the reversed halo sign in neutropenic patients compared with non-neutropenic patients: Data from a single-centre study involving 27 patients with pulmonary mucormycosis (2003-2016).

Author: Bourcier J, Heudes PM, Morio F, Gastinne T, Chevallier P, Rialland-Battisti F, Garandeau C, Danner-Boucher I, Le Pape P, Frampas E, Moreau P, Defrance C, and Peterlin P
Subjects: Adolescent, Adult, Age Distribution, Aged, Child, Child, Preschool, Female, Humans, Lung Diseases, Fungal diagnostic imaging, Lung Diseases, Fungal epidemiology, Male, Middle Aged, Mucormycosis diagnostic imaging, Mucormycosis epidemiology, Neutropenia diagnosis, Neutropenia epidemiology, Neutropenia microbiology, Prevalence, Retrospective Studies, Sex Distribution, Tomography, X-Ray Computed, Young Adult, Lung Diseases, Fungal diagnosis, Mucormycosis diagnosis
Abstract: Pulmonary mucormycosis (PM) is a life-threatening infection and the diagnosis can be challenging. The objective was to retrospectively explore the value of the RHS in our cohort of 27 patients with mucormycosis and its relation to neutropenia. This was a retrospective study including all patients with a diagnosis of probable or proven invasive PM according to the 2008 EORTC/MSG criteria between September 2003 to April 2016. Fisher's exact test and Mann-Whitney test, with a P-value statistically significant under .05 (P<.05), were used to compare neutropenic and non-neutropenic groups. 27 patients were eligible. The RHS could be identified in 78% of cases in the neutropenic group, and was less common in the non-neutropenic group (31%) (P<.05). Reticulations inside ground-glass opacity in case of RHS were present in 13 out of 15 patients (87%). Mucorales DNA detection by PCR on serum provided, a median time to the first PCR-positive sample of 3 days (-33 to +60 days) before diagnosis was confirmed. Six patients had IPA co-infection. In conclusion, RHS is more frequent in case of PM in neutropenic patients compare to non-neutropenic patients. Its presence in immunocompromised patients should be sufficient to promptly start Mucorales-active antifungal treatment, while its absence especially in non-neutropenic cases should not be sufficient to exclude the diagnosis., (© 2017 Blackwell Verlag GmbH.)
Published: 2017
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19. Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia.

Author: Mohty M, Malard F, Blaise D, Milpied N, Socié G, Huynh A, Reman O, Yakoub-Agha I, Furst S, Guillaume T, Tabrizi R, Vigouroux S, Peterlin P, El-Cheikh J, Moreau P, Labopin M, and Chevallier P
Subjects: Adenine Nucleotides administration & dosage, Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Arabinonucleosides administration & dosage, Clofarabine, Cytarabine administration & dosage, Drug Resistance, Neoplasm, Female, Graft Survival, Graft vs Host Disease diagnosis, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Humans, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute mortality, Male, Middle Aged, Retreatment, Survival Analysis, Tissue Donors, Transplantation Chimera, Transplantation, Homologous, Treatment Outcome, Young Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Leukemia, Myeloid, Acute therapy, Transplantation Conditioning methods
Abstract: The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients' outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m 2 /day) and cytosine arabinoside (1 g/m 2 /day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33-71) at 1 year and 38% (95% CI: 18-46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26-64) at 1 year and 29% (95% CI: 13-48) at 2 years. The cumulative incidence of non-relapse mortality was 8% (95% CI: 1-24) at 1 year and 12% (95% CI: 3-19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174., (Copyright© Ferrata Storti Foundation.)
Published: 2017
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20. Late Complications and Quality of Life after Reduced-Intensity Conditioning Allogeneic Stem Cell Transplantation.

Author: Clavert A, Peric Z, Brissot E, Malard F, Guillaume T, Delaunay J, Dubruille V, Le Gouill S, Mahe B, Gastinne T, Blin N, Harousseau JL, Moreau P, Milpied N, Mohty M, and Chevallier P
Subjects: Adult, Aged, Cardiovascular Diseases etiology, Follow-Up Studies, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation methods, Humans, Lung Diseases etiology, Male, Middle Aged, Neoplasms, Second Primary etiology, Surveys and Questionnaires, Survivors psychology, Transplantation Conditioning adverse effects, Transplantation, Homologous, Young Adult, Hematopoietic Stem Cell Transplantation adverse effects, Quality of Life psychology, Transplantation Conditioning methods
Abstract: Late complications (LC) and quality of life (QOL) were analyzed in 110 adult patients who underwent reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (allo-SCT) and were alive for more than 2 years after allo-SCT. Overall survival of these patients was 93% (95% confidence interval [CI], 88% to 99%) and 81% (95% CI, 71% to 94%) at 5 and 10 years, respectively. The primary cause of death was a recurrence of primary malignancy. With a median follow-up of 4.6 years (range, 2 to 12.1), chronic graft-versus-host disease (cGVHD) was the most prevalent late effect, with a cumulative incidence of 66% (95% CI, 57% to 74%) at 10 years. Cardiovascular complications were the most prevalent LC with a cumulative incidence of 47% (95% CI, 35% to 59%), followed by pulmonary complications with a cumulative incidence of 33% (95% CI, 21% to 46%) and renal impairment with a cumulative incidence of 34% (95% CI, 25% to 43%) at 10 years. Secondary malignancies occurred with a cumulative incidence of 11% (95% CI, 5% to 20%) at 10 years. In this series, 61 patients (55%) responded to QOL survey. With the use of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and Functional Assessment of Cancer Therapy-Bone Marrow Transplant questionnaires, most of the patients reported good to excellent QOL and patients with cGVHD had significantly lower QOL than patients without cGVHD. In conclusion, QOL after RIC is comparable to that seen after myeloablative conditioning, while the natural history of LC after RIC appears to be different from that described in the standard myeloablative setting, warranting further research in this field., (Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
Published: 2017
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21. Successful treatment of acute promyelocytic leukemia with arsenic trioxide and all-trans retinoic acid in a double lung and kidney transplanted patient.

Author: Peterlin P, Garnier A, Tissot A, Garandeau C, Houreau-Langlard D, Hourmant M, Vantyghem S, Bonnet A, Guillaume T, Béné MC, Le Gouill S, Moreau P, and Chevallier P
Subjects: Arsenic Trioxide, Arsenicals administration & dosage, Carcinoma, Squamous Cell etiology, Humans, Immunocompromised Host, Leukemia, Promyelocytic, Acute etiology, Male, Middle Aged, Neoplasms, Second Primary etiology, Oxides administration & dosage, Skin Neoplasms etiology, Tretinoin administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Kidney Transplantation, Leukemia, Promyelocytic, Acute drug therapy, Lung Transplantation, Postoperative Complications drug therapy
Published: 2016
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22. Allogeneic stem cell transplantation for patients with mantle cell lymphoma who failed autologous stem cell transplantation: a national survey of the SFGM-TC.

Author: Tessoulin B, Ceballos P, Chevallier P, Blaise D, Tournilhac O, Gauthier J, Maillard N, Tabrizi R, Choquet S, Carras S, Ifrah N, Guillerm G, Mohty M, Tilly H, Socie G, Cornillon J, Hermine O, Daguindau É, Bachy E, Girault S, Marchand T, Oberic L, Reman O, Leux C, and Le Gouill S
Subjects: Adult, Aged, Female, France, Graft vs Host Disease etiology, Hematopoietic Stem Cell Transplantation mortality, Humans, Lymphoma, Mantle-Cell complications, Lymphoma, Mantle-Cell mortality, Male, Middle Aged, Salvage Therapy mortality, Surveys and Questionnaires, Survival Analysis, Transplantation Conditioning methods, Transplantation, Autologous adverse effects, Transplantation, Autologous mortality, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Mantle-Cell therapy, Salvage Therapy methods, Transplantation, Homologous adverse effects, Transplantation, Homologous methods, Transplantation, Homologous mortality
Abstract: Poly-chemotherapy plus rituximab followed by autologous stem cell transplantation (auto-SCT) is standard care for untreated young patients with mantle cell lymphoma (MCL). Despite this intensive treatment, transplant patients remain highly susceptible to relapse over time. The French SFGM-TC performed a national survey on reduced-intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) for fit relapsed/refractory patients who failed after auto-SCT (n=106). Median times of relapse after auto-SCT, and from auto-SCT to RIC-allo-SCT were 28 months and 3.6 years, respectively. Sixty per cent of patients received at least three lines of treatment before RIC-allo-SCT. Conditioning regimens for RIC-allo-SCT were heterogeneous. Twenty patients experienced grade III/IV aGvHD, extensive cGvHD was reported in 28 cases. Median follow-up after RIC-allo-SCT was 45 months. Median PFS after RIC-allo-SCT was 30.1 months and median overall survival was 62 months. Treatment-related mortality (TRM) at 1 year and 3 years were estimated at 28% and 32%, respectively. A total of 52 patients died; major causes of death were related to toxicity (n=34) and MCL (n=11). Patients in good response before RIC-allo-SCT experienced a better PFS and OS. Our work highlights the need for new RIC-allo-SCT MCL-tailored approaches to reduce TRM, and early and late relapse.
Published: 2016
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23. Higher Early Monocyte and Total Lymphocyte Counts Are Associated with Better Overall Survival after Standard Total Body Irradiation, Cyclophosphamide, and Fludarabine Reduced-Intensity Conditioning Double Umbilical Cord Blood Allogeneic Stem Cell Transplantation in Adults.

Author: Le Bourgeois A, Peterlin P, Guillaume T, Delaunay J, Duquesne A, Le Gouill S, Moreau P, Mohty M, Campion L, and Chevallier P
Subjects: Adolescent, Adult, Aged, Cord Blood Stem Cell Transplantation mortality, Cyclophosphamide administration & dosage, Female, Graft Survival, Granulocyte Colony-Stimulating Factor therapeutic use, Humans, Leukocyte Count, Lymphocyte Count, Male, Middle Aged, Transplantation Conditioning mortality, Transplantation, Homologous, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Whole-Body Irradiation, Young Adult, Cord Blood Stem Cell Transplantation methods, Lymphocytes cytology, Monocytes cytology, Transplantation Conditioning methods
Abstract: This single-center retrospective study aimed to report the impact of early hematopoietic and immune recoveries after a standard total body irradiation, cyclophosphamide, and fludarabine (TCF) reduced-intensity conditioning (RIC) regimen for double umbilical cord blood (dUCB) allogeneic stem cell transplantation (allo-SCT) in adults. We analyzed 47 consecutive patients older than 17 years who engrafted after a dUCB TCF allo-SCT performed between January 2006 and April 2013 in our department. Median times for neutrophil and platelet recoveries were 17 (range, 6 to 59) and 37 days (range, 0 to 164), respectively. The 3-year overall (OS) and disease-free survivals, relapse incidence, and nonrelapse mortality were 65.7%, 57.2%, 27.1%, and 19%, respectively. In multivariate analysis, higher day +30 monocyte (≥615/mm(3); hazard ratio [HR], .04; 95% confidence interval [CI], .004 to .36; P < .01) and day +42 lymphocyte (≥395/mm(3); HR, .16; 95% CI, .03 to .78; P = .02) counts were independently associated with better OS. These results suggest that early higher hematopoietic and immune recovery is predictive of survival after dUCB TCF RIC allo-SCT in adults. Factors other than granulocyte colony-stimulating factor, which was used in all cases, favoring expansion of monocytes or lymphocytes, should be tested in the future as part of the UCB transplantation procedure., (Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
Published: 2016
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24. Impact of pre-transplant diffusion lung capacity for nitric oxide (DLNO) and of DLNO/pre-transplant diffusion lung capacity for carbon monoxide (DLNO/DLCO) ratio on pulmonary outcomes in adults receiving allogeneic stem cell transplantation for hematological diseases.

Author: Le Bourgeois A, Malard F, Chevallier P, Urbistandoy G, Guillaume T, Delaunay J, Peterlin P, Lemarchand P, Germaud P, Mohty M, Moreau P, and Chambellan A
Subjects: Adult, Aged, Allografts, Female, Humans, Lung Volume Measurements, Male, Middle Aged, Carbon Monoxide metabolism, Hematologic Diseases metabolism, Hematologic Diseases mortality, Hematologic Diseases physiopathology, Hematologic Diseases therapy, Hematopoietic Stem Cell Transplantation, Nitric Oxide metabolism
Published: 2016
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25. Improvement of overall survival after allogeneic hematopoietic stem cell transplantation for children and adolescents: a three-decade experience of a single institution.

Author: Brissot E, Rialland F, Cahu X, Strullu M, Corradini N, Thomas C, Blin N, Rialland X, Thebaud E, Chevallier P, Moreau P, Milpied N, Harousseau JL, Mechinaud F, and Mohty M
Subjects: Adolescent, Adult, Allografts, Child, Child, Preschool, Disease-Free Survival, Follow-Up Studies, Humans, Infant, Retrospective Studies, Survival Rate, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation
Abstract: Allogeneic stem cell transplantation (allo-SCT) has become an essential component of the treatment for a variety of diseases in pediatric patients. During the past decades, advances in the transplant technology, availability of hematopoietic stem cells and supportive care not only have resulted in improved outcomes, but also have expanded the transplant options. However, these features have been studied mainly in adult populations. This investigation analyzed changes in patient profile, transplantation, graft characteristics and outcome among 250 children and adolescent patients who received allo-SCT in a single center between 1983 and 2010. In the 2000-2010, compared with the 1983-1999 period, a significantly higher 5-year overall survival (64% versus 52%, P=0.03) was observed together with a significant decrease of non-relapse mortality (27% versus 9%, P=0.0002). The progression-free survival was comparable between the two periods (49% versus 57%; P=0.17). The 5-year cumulative incidence of relapse was 24% between 1983 and 1999, and 34% between 2000 and 2010 (P=0.08). Major advances in supportive care practice have been made over the past decade, resulting in a significant survival benefit for the pediatric population undergoing allo-SCT. However, post-transplant relapse remains the leading cause of failure of this therapeutic approach, and preventing relapse represents a major challenge today.
Published: 2016
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26. Comparison of umbilical cord blood allogeneic stem cell transplantation vs. auto-SCT for adult acute myeloid leukemia patients in second complete remission at transplant: a retrospective study on behalf of the SFGM-TC.

Author: Chevallier P, Labopin M, Socie G, Rubio MT, Blaise D, Vigouroux S, Huynh A, Michallet M, Bay JO, Maury S, Yakoub-Agha I, Fegueux N, Deconinck E, Contentin N, Maillard N, Bulabois CE, Francois S, Oumedaly R, Raus N, and Mohty M
Subjects: Adult, Aged, Female, Humans, Leukemia, Myeloid, Acute diagnosis, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute pathology, Male, Middle Aged, Multivariate Analysis, Prognosis, Recurrence, Remission Induction, Retrospective Studies, Survival Analysis, Transplantation, Autologous, Transplantation, Homologous, Antineoplastic Agents therapeutic use, Cord Blood Stem Cell Transplantation, Hematopoietic Stem Cell Transplantation, Leukemia, Myeloid, Acute therapy, Registries, Transplantation Conditioning methods
Abstract: This retrospective study considered the outcomes of 181 patients with acute myeloid leukemia (AML) transplanted in second complete remission (CR2) between January 2005 and April 2012 and who received either a myeloablative autologous stem cell transplant (Auto-SCT; n = 82; median age: 48 years; median follow-up: 45 months) or an umbilical cord blood (UCB) allogeneic SCT (n = 99, median age: 46 years; median follow-up: 36 months; conditioning regimens: myeloablative n = 21, reduced n = 78; single unit n = 37, double units n = 62). Although the Auto group showed a significant better prognostic profile at transplant, with longer median interval between diagnosis and time of graft, higher incidence of good-risk cytogenetics and lower number of previously transplanted patients, 3-year OS and LFS were similar between both groups (Auto: 59 ± 6% vs. 50 ± 6%, P = 0.45; and 57 ± 6% vs. 46 ± 6%, P = 0.37). In multivariate analysis, UCB allo-SCT was associated with lower relapse incidence (HR: 0.3, 95% CI: 0.11-0.82, P = 0.02), but higher non-relapse mortality (NRM) (HR: 4.16; 95% CI: 1.46-11.9, P = 0.008). Results from this large study suggest that UCB allo-SCT provides better disease control than auto-SCT, which is especially important in the setting of high-risk disease. However, this disease control advantage is counterbalanced by higher toxicity, highlighting the need for novel approaches aiming to decrease NRM after UCB allo-SCT., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Published: 2015
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27. Initial fluconazole prophylaxis may not be required in adults with acute leukemia or myelodysplastic/myeloproliferative disorders after reduced intensity conditioning peripheral blood stem cell allogeneic transplantation.

Author: Brissot E, Cahu X, Guillaume T, Delaunay J, Ayari S, Peterlin P, Le Bourgeois A, Harousseau JL, Milpied N, Bene MC, Moreau P, Mohty M, and Chevallier P
Subjects: Acute Disease, Adult, Aged, Female, Humans, Leukemia epidemiology, Male, Middle Aged, Mycoses epidemiology, Myelodysplastic Syndromes epidemiology, Myeloproliferative Disorders epidemiology, Neoadjuvant Therapy, Opportunistic Infections epidemiology, Opportunistic Infections prevention & control, Retrospective Studies, Transplantation, Homologous, Young Adult, Chemoprevention methods, Fluconazole therapeutic use, Leukemia therapy, Mycoses prevention & control, Myelodysplastic Syndromes therapy, Myeloproliferative Disorders therapy, Peripheral Blood Stem Cell Transplantation adverse effects, Transplantation Conditioning adverse effects, Transplantation Conditioning methods
Abstract: In the myeloablative transplant setting, the early use of fluconazole prophylaxis provides a benefit in overall survival. Recent changes in transplantation practices, including the use of peripheral blood stem cells (PBSC) and/or reduced intensity conditioning (RIC) regimen may have favorably impacted the epidemiology of invasive fungal infections (IFI) after allogeneic stem cell transplantation (allo-SCT). Yet, the impact of removing fluconazole prophylaxis after RIC PBSC allotransplant is ill known. Here, a retrospective analysis was performed comparing patients who received fluconazole as antifungal prophylaxis (n = 53) or not (n = 56) after allo-SCT for acute leukemia or myelodysplastic/myeloproliferative syndrome. Sixteen IFI were documented (14 %) at a median time of 103 days after transplantation, including eight before day +100, at a similar rate, whether the patients received fluconazole prophylaxis (13 %) or not (16 %). IFI were due mainly to Aspergillus species (87 %), and only two Candida-related IFI (13 %) were documented in the non-fluconazole group before day +100. The incidences of IFI (overall, before or after day +100) as well as 3-year overall and disease-free survival, non-relapse mortality, or acute and chronic graft-versus-host disease (GVHD) were similar between both groups. In conclusion, this study suggests that fluconazole may not be required at the initial phase of RIC allo-SCT using PBSC. This result has to be confirmed prospectively while Aspergillus prophylaxis should be discussed in this particular setting.
Published: 2015
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28. Complete donor T cell chimerism predicts lower relapse incidence after standard double umbilical cord blood reduced-intensity conditioning regimen allogeneic transplantation in adults.

Author: Peterlin P, Delaunay J, Guillaume T, Gastinne T, Mahé B, Dubruille V, Blin N, Le Bourgeois A, Brissot E, Lodé L, Le Gouill S, Moreau P, Mohty M, and Chevallier P
Subjects: Adolescent, Adult, Aged, Cyclophosphamide therapeutic use, Female, Graft Survival, Graft vs Host Disease drug therapy, Graft vs Host Disease immunology, Graft vs Host Disease mortality, Graft vs Host Disease pathology, Hematologic Neoplasms immunology, Hematologic Neoplasms mortality, Hematologic Neoplasms pathology, Humans, Immunosuppressive Agents therapeutic use, Male, Middle Aged, Prognosis, Recurrence, Retrospective Studies, Survival Analysis, T-Lymphocytes cytology, T-Lymphocytes transplantation, Transplantation, Autologous, Transplantation, Homologous, Treatment Outcome, Unrelated Donors, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Whole-Body Irradiation, Cord Blood Stem Cell Transplantation methods, Hematologic Neoplasms therapy, Myeloablative Agonists therapeutic use, T-Lymphocytes immunology, Transplantation Chimera immunology, Transplantation Conditioning methods
Abstract: Double umbilical cord blood (dUCB) allogeneic transplantation after a low-dose total body irradiation, cyclophosphamide, and fludarabine (TCF)-based reduced-intensity conditioning regimen (RIC) is increasingly used in adults lacking a suitable related or unrelated donor. Currently, there are little data regarding the long-term outcome of CD3(+) T cell chimerism (TCC) in this particular setting. Thirty-six adults with various hematological diseases who received dUCB allogeneic transplants conditioned with TCF were included in this retrospective study. Peripheral blood CD3(+) TCC was considered until day +100 after transplantation to determine the impact of full versus mixed chimerism on long-term outcomes. Twenty-nine and 7 patients were documented with full and mixed CD3(+) TCC, respectively, within the first 100 days after transplantation. With a median follow-up of 36 months, 3 year-overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR) were 61%, (95% confidence interval [CI], 43% to 75%); 50% (95% CI, 32.5% to 66%), and 28% (95% CI, 16% to 44%), respectively. In univariate analysis, a full CD3(+) TCC was associated with a better 3-year DFS: 59% (95% CI, 39% to 75.5%) versus 14% (95% CI, 7% to 46%); hazard ratio (HR), .24 (.09 to .65); P = .005 and a lower CIR: 24% (95% CI, 21.5% to 57%) versus 78% (95% CI, 52% to 99%); HR, .18 (.05 to .50); P = .004. In multivariate analysis, a full CD3(+) TCC remained associated with a lower CIR (HR, .17 [.028 to .99]; P = .049). CD3(+) TCC has no impact on graft-versus-host disease and nonrelapse mortality in this study. In conclusion, here, full CD3(+) TCC was independently associated with a lower risk of relapse in adults receiving a dUCB TCF RIC allogeneic transplantation. This highlights the need to develop immunotherapy approaches allowing for early conversion to full chimerism after this type of transplantation., (Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
Published: 2015
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29. Reduced-toxicity conditioning prior to allogeneic stem cell transplantation improves outcome in patients with myeloid malignancies.

Author: Oudin C, Chevallier P, Furst S, Guillaume T, El Cheikh J, Delaunay J, Castagna L, Faucher C, Granata A, Devillier R, Chabannon C, Esterni B, Vey N, Mohty M, and Blaise D
Subjects: Adolescent, Adult, Aged, Comorbidity, Female, Graft vs Host Disease etiology, Humans, Karyotype, Leukemia, Myeloid, Acute diagnosis, Male, Middle Aged, Myelodysplastic Syndromes diagnosis, Neoplasm Staging, Recurrence, Transplantation, Homologous, Treatment Outcome, Young Adult, Hematopoietic Stem Cell Transplantation adverse effects, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute therapy, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Transplantation Conditioning adverse effects
Abstract: The introduction of reduced intensity/toxicity conditioning regimens has allowed allogeneic hematopoietic cell transplantation to be performed in patients who were previously considered too old or otherwise unfit. Although it led to a reduction in non-relapse mortality, disease control remains a major challenge. We studied the outcome of 165 patients with acute myeloid leukemia (n=124) or myelodysplastic syndrome (n=41) transplanted after conditioning with fludarabine (30 mg/m(2)/day for 5 days), intravenous busulfan (either 260 mg/m(2): reduced intensity conditioning, or 390-520 mg/m(2): reduced toxicity conditioning), and rabbit anti-thymoglobulin (2.5 mg/kg/day for 2 days). The median age of the patients at transplantation was 56.8 years. The 2-year relapse incidence was 29% (23% versus 39% for patients transplanted in first complete remission and those transplanted beyond first complete remission, respectively; P=0.008). The 2-year progression-free survival rate was 57% (95% CI: 49.9-65). It was higher in the groups with favorable or intermediate cytogenetics than in the group with unfavorable cytogenetics (72.7%, 60.5%, and 45.7%, respectively; P=0.03). The cumulative incidence of grades 2-4 and 3-4 acute graft-versus-host disease at day 100 was 19.3% and 7.9%, respectively. The cumulative incidence of chronic graft-versus-host disease at 1 year was 21.6% (severe forms: 7.8%). Non-relapse mortality at 1 year reached 11%. The 2-year overall survival rate was 61.8% (95% CI: 54.8-69.7). Unfavorable karyotype and disease status beyond first complete remission were associated with a poorer survival. This well-tolerated conditioning platform can lead to long-term disease control and offers possibilities of modulation according to disease stage or further development., (Copyright© Ferrata Storti Foundation.)
Published: 2014
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30. Long-lasting HHV-6 reactivation in long-term adult survivors after double umbilical cord blood allogeneic stem cell transplantation.

Author: Illiaquer M, Malard F, Guillaume T, Imbert-Marcille BM, Delaunay J, Le Bourgeois A, Rimbert M, Bressollette-Bodin C, Precupanu C, Ayari S, Peterlin P, Moreau P, Mohty M, and Chevallier P
Subjects: Adult, Aged, Female, Fetal Blood transplantation, Herpesvirus 6, Human immunology, Humans, Incidence, Male, Middle Aged, Prospective Studies, Young Adult, Hematopoietic Stem Cell Transplantation adverse effects, Herpesviridae Infections immunology, Herpesvirus 6, Human physiology, Virus Activation immunology
Abstract: Higher incidence of human herpesvirus 6 (HHV-6) infection has been documented after umbilical cord blood allo-transplant in adults. Here we demonstrate that HHV-6 reactivation persists for a very long time in half of the patients after this type of graft. Long-term immune reconstitution does not explain this event, which remains to be explained., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
Published: 2014
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31. Continuous reduced nonrelapse mortality after allogeneic hematopoietic stem cell transplantation: a single-institution's three decade experience.

Author: Malard F, Chevallier P, Guillaume T, Delaunay J, Rialland F, Harousseau JL, Moreau P, Mechinaud F, Milpied N, and Mohty M
Subjects: Adolescent, Adult, Aged, Female, Hematopoietic Stem Cell Transplantation mortality, Humans, Male, Middle Aged, Retrospective Studies, Survival Analysis, Transplantation Conditioning mortality, Transplantation, Homologous mortality, Young Adult, Hematopoietic Stem Cell Transplantation adverse effects, Transplantation Conditioning adverse effects, Transplantation, Homologous adverse effects
Abstract: This study analyzed changes in patients, transplantation, graft characteristics, and outcome among 827 patients who received their first allo-SCT in a single center between 1983 and 2010. In the 2001 to 2010 decade, compared with the 1983 to 1990 and 1991 to 2000 decades, patients were significantly older and presented with higher risk diseases, reduced intensity conditioning and alternative donors were used more often, and stem cell sources changed from bone marrow to peripheral blood stem cells and cord blood. In the 2001 to 2010 decade, we observed a significant decrease in nonrelapse mortality (NRM) (P = .0007 and P < .0001, respectively) and an increase in relapse incidence (P = .04 and P = .009, respectively), but overall survival (OS) was increased (P = .11 and P = .009, respectively), and there was a trend towards an increased progression-free survival (P = .30 and P = .09, respectively), as compared with the 1983 to 1990 and 1991 to 2000 decades. Chronic graft-versus-host disease (GVHD) was significantly increased, whereas grades III to IV acute GVHD remained stable. These data suggest that, despite the fact that older and higher risk patients with more comorbidities underwent transplantation in the last 10 years, NRM decreased while the incidence of relapse increased and the OS improved., (Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
Published: 2014
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32. Early detection of acute graft-versus-host disease by wireless capsule endoscopy and probe-based confocal laser endomicroscopy: results of a pilot study.

Author: Coron E, Laurent V, Malard F, Le Rhun M, Chevallier P, Guillaume T, Mosnier JF, Galmiche JP, and Mohty M
Abstract: Objective: Acute gastrointestinal graft-versus-host disease (GI-GVHD) is usually diagnosed using endoscopic examinations and biopsies for conventional histology. The aim of this pilot study was to determine whether mini-invasive techniques such as probe-based confocal laser endomicroscopy (pCLE) combined with wireless capsule endoscopy (WCE) could detect early lesions of GI-GVHD prior to symptoms., Design: Fifteen patients undergoing allogeneic haematopoietic stem cell transplantation (allo-HSCT) were prospectively examined with a small bowel WCE, duodenal and colorectal pCLE, and standard biopsies. Per study protocol, all these examinations were scheduled between day 21 and day 28 after allo-HSCT, independently of the presence or absence of digestive symptoms., Results: During follow up, eight patients developed acute GI-GVHD. Sensitivity of WCE, pCLE, and histology were 50, 87.5, and 50%, respectively. Specificity of WCE, pCLE, and histology were 80, 71.5, and 80%, respectively. We showed a positive correlation between the Glücksberg scoring system and WCE (rho = 0.543, p = 0.036) and pCLE (rho = 0.727, p = 0.002) but not with standard histology (rho = 0.481, p = 0.069)., Conclusions: The results from this pilot study suggest that novel methods such as pCLE and WCE could be part of a mini-invasive algorithm for early detection of GI-GVHD.
Published: 2014
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33. Stable long-term pulmonary function after fludarabine, antithymocyte globulin and i.v. BU for reduced-intensity conditioning allogeneic SCT.

Author: Dirou S, Malard F, Chambellan A, Chevallier P, Germaud P, Guillaume T, Delaunay J, Moreau P, Delasalle B, Lemarchand P, and Mohty M
Subjects: Administration, Intravenous, Adult, Aged, Antilymphocyte Serum administration & dosage, Busulfan administration & dosage, Female, Follow-Up Studies, Hematologic Diseases mortality, Humans, Immunosuppressive Agents administration & dosage, Lung Diseases etiology, Male, Middle Aged, Myeloablative Agonists administration & dosage, Respiratory Function Tests, Retrospective Studies, Stem Cell Transplantation adverse effects, Stem Cell Transplantation mortality, Transplantation Conditioning mortality, Transplantation, Homologous, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Young Adult, Hematologic Diseases therapy, Lung Diseases prevention & control, Lymphocyte Depletion methods, Stem Cell Transplantation methods, Transplantation Conditioning methods
Abstract: Lung function decline is a well-recognized complication following allogeneic SCT (allo-SCT). Reduced-intensity conditioning (RIC) and in vivo T-cell depletion by administration of antithymocyte globulin (ATG) may have a protective role in the occurrence of late pulmonary complications. This retrospective study reported the evolution of lung function parameters within the first 2 years after allo-SCT in a population receiving the same RIC regimen that included fludarabine and i.v. BU in combination with low-dose ATG. The median follow-up was 35.2 months. With a median age of 59 years at the time of transplant, at 2 years, the cumulative incidences of non-relapse mortality was as low as 9.7%. The cumulative incidence of relapse was 33%. At 2 years, the cumulative incidences of extensive chronic GVHD (cGVHD) and of pulmonary cGVHD were 23.1% and 1.9%, respectively. The cumulative incidences of airflow obstruction and restrictive pattern were 3.8% and 9.6%, respectively. Moreover, forced expiratory volume (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio remained stable from baseline up to 2 years post transplantation (P=0.26, P=0.27 and P=0.07, respectively). These results correspond favorably with the results obtained with other RIC regimens not incorporating ATG, and suggest that ATG may have a protective pulmonary role after allo-SCT.
Published: 2014
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34. Azacitidine salvage therapy for relapse of myeloid malignancies following allogeneic hematopoietic SCT.

Author: Tessoulin B, Delaunay J, Chevallier P, Loirat M, Ayari S, Peterlin P, Le Gouill S, Gastinne T, Moreau P, Mohty M, and Guillaume T
Subjects: Adolescent, Adult, Aged, Female, Hematologic Neoplasms therapy, Hematopoietic Stem Cell Transplantation adverse effects, Humans, Male, Middle Aged, Neoplasm Recurrence, Local drug therapy, Prognosis, Retrospective Studies, Salvage Therapy methods, Transplantation, Homologous, Young Adult, Azacitidine therapeutic use, Hematologic Neoplasms drug therapy, Hematopoietic Stem Cell Transplantation methods
Abstract: Patients with hematopoietic malignancies relapsing after allogeneic hematopoietic SCT (allo-HSCT) have a poor prognosis. We retrospectively analyzed the patients who received azacitidine in our center in the course of treatment of their post-transplant relapse. We identified 31 patients. Relapse occurred at a median of 3.7 (1.7-37.6) months following allo-HSCT. Patients received a median number of three cycles (1-12) of azacitidine (7 days, 75 mg/m(2) daily). Thirty-nine percent of patients had either a monosomal karyotype or a complex karyotype. Eleven patients (35%) received at least one DLI. Eleven patients responded to azacitidine, with four patients achieving a CR (13%). Median time to best response was 92 (35-247) days, with a median duration of 209 (64-751) days. One-year estimated survival rate was 14%. In conclusion, azacitidine may reinduce durable remissions in very few patients with AML or myelodysplastic syndrome. The toxicity related to azacitidine was high, although it may be difficult to distinguish between treatment-related side effects, namely due to cytopenia and toxicity due to the relapse or disease progression itself. Early administration of azacitidine after transplant followed by DLI should be considered as a pre-emptive therapy for potential relapse in patients with minimal residual disease or high-risk myeloid malignancies.
Published: 2014
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35. Increased Th17/Treg ratio in chronic liver GVHD.

Author: Malard F, Bossard C, Brissot E, Chevallier P, Guillaume T, Delaunay J, Mosnier JF, Moreau P, Grégoire M, Gaugler B, and Mohty M
Subjects: Adult, Aged, Animals, Biopsy, Female, Graft vs Host Disease pathology, Humans, Liver Diseases pathology, Male, Mice, Middle Aged, T-Lymphocytes, Regulatory immunology, Th17 Cells immunology, Graft vs Host Disease immunology, Liver Diseases immunology, T-Lymphocytes, Regulatory pathology, Th17 Cells pathology
Abstract: The contribution of Th17 cells to chronic GVHD (cGVHD) has been demonstrated in cGVHD mouse models. However, their contribution to human liver cGVHD remains unclear. We evaluated Th17 cells in biopsies from a cohort of 17 patients with liver cGVHD. We observed a significant increase in Th17 cells in the liver of patients with cGVHD, as demonstrated by an increase in CCR6+, CD161+ and RORγt+ T cells (P=0.03, P=0.0001 and P=0.03, respectively). We also assessed the presence of Th1 and regulatory (Treg) T cells: the numbers of Th1 and Treg cells were very low, with no difference between the two groups (P=0.88 and P=0.12, respectively). Furthermore, Th17/Th1 and Th17/Treg ratios were significantly increased in the liver of patients with liver cGVHD (P=0.005 and P=0.002, respectively). This study provides evidence for an infiltration by Th17 cells in the liver of patients with cGVHD and an increased Th17/Treg ratio, suggesting a defect in the regulatory mechanism driven by Treg cells or an inappropriate activation of effectors cells, especially Th17 cells, or both mechanisms, in human liver cGVHD.
Published: 2014
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36. Outcomes of adults with active or progressive hematological malignancies at the time of allo-SCT: a survey from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

Author: Chevallier P, Labopin M, Milpied N, Bilger K, Socié G, Yakoub-Agha I, Michallet M, Bulabois CE, Maury S, Beguin Y, Bay JO, Blaise D, Maillard N, Guillerm G, Daguindeau E, Raus N, and Mohty M
Subjects: Adolescent, Adult, Aged, Disease Progression, Disease-Free Survival, Female, France, HLA Antigens chemistry, Hodgkin Disease mortality, Hodgkin Disease therapy, Humans, Lymphoma, Non-Hodgkin mortality, Lymphoma, Non-Hodgkin therapy, Male, Middle Aged, Myelodysplastic Syndromes mortality, Myelodysplastic Syndromes therapy, Myeloproliferative Disorders mortality, Myeloproliferative Disorders therapy, Proportional Hazards Models, Recurrence, Retrospective Studies, Societies, Medical, Treatment Outcome, Young Adult, Hematologic Neoplasms mortality, Hematologic Neoplasms therapy, Stem Cell Transplantation, Transplantation, Homologous
Abstract: Previous data suggested that allo-SCT might be an effective therapy in the setting of chemo-refractory/relapsed diseases because of the potent long-term immune-mediated tumor control. This retrospective study aimed to analyze the outcome of adult patients who received allo-SCT in a chemo-refractory/relapsed status. The series included 840 patients with active or progressive disease at the time of transplant. Median age was 50 years. With a median follow-up of 40 months, 3-year OS, disease-free survival (DFS), and non-relapse mortality rates were 29±2, 23±2, and 30±2%, respectively. At the last follow-up, 252 patients (30%) were still alive (of whom 201 were in CR (24%). In a Cox multivariate analysis, the use of a reduced-intensity conditioning (RIC) before allo-SCT and use of an HLA-identical sibling donor remained independently associated with a better OS (hazard ratio (HR)=0.82; 95% confidence interval (CI), 0.69-0.98, P=0.03; and HR=0.79; 95% CI, 0.66-0.93, P=0.006, respectively). Also, a diagnosis of myelodysplastic syndrome/myeloproliferative disorder, Hodgkin lymphoma and non-Hodgkin lymphoma compared with acute leukemia had a favorable impact on OS (HR=0.55; 95% CI, 0.45-0.68, P<0.0001; HR=0.49; 95% CI, 0.31-0.75, P=0.001; and HR=0.47; 95% CI, 0.35-0.63, P<0.0001, respectively). In conclusion, this study suggests that allo-SCT may be of benefit in some subgroups of patients with active or progressive hematological malignancies at the time of allo-SCT.
Published: 2014
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37. 18F-FDG PET/CT for the assessment of gastrointestinal GVHD: results of a pilot study.

Author: Bodet-Milin C, Lacombe M, Malard F, Lestang E, Cahu X, Chevallier P, Guillaume T, Delaunay J, Brissot E, Moreau P, Kraeber-Bodere F, and Mohty M
Subjects: Adult, Aged, False Negative Reactions, False Positive Reactions, Female, Hematologic Diseases complications, Humans, Male, Middle Aged, Multimodal Imaging, Pilot Projects, Positron-Emission Tomography, Prospective Studies, Radiopharmaceuticals, Reproducibility of Results, Sensitivity and Specificity, Tomography, X-Ray Computed, Transplantation Conditioning, Young Adult, Fluorodeoxyglucose F18, Gastrointestinal Diseases diagnostic imaging, Graft vs Host Disease diagnostic imaging, Hematologic Diseases therapy
Abstract: This prospective pilot study aimed to evaluate the predictive value of (18)F-FDG PET/CT for early diagnosis of acute gastrointestinal GVHD (GI-GVHD). In all, 42 consecutive patients who received allo-SCT were included. (18)F-FDG PET/CT was systematically performed at a median of 28 (range, 24-38) days after allo-SCT. (18)F-FDG PET/CT data review was positive in 15 cases (36%) (9 true positive (TP) cases and 6 false positive (FP) cases) and negative in 27 cases (64%; 26 true negative (TN) cases and 1 false negative (FN) case) at visual analysis. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of (18)F-FDG PET/CT for the diagnosis of acute GI-GVHD were, respectively, 81%, 90%, 60%, 96% and 83%. There were no significant differences of SUVmax values between grade 1-2 GI-GVHD and severe grade 3-4 GI-GVHD. Overall, these preliminary findings suggested that the inflammatory activity of the gastrointestinal tract associated with acute GI-GVHD could be assessed by (18)F-FDG PET/CT suggesting that noninvasive (18)F-FDG PET/CT could become a valuable examination to be performed shortly before endoscopy to map acute GI-GVHD lesions, guide the biopsy sites and choose the appropriate endoscopic procedure, especially in those asymptomatic patients with a positive (18)F-FDG PET/CT.
Published: 2014
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38. BCR-ABL1 molecular remission after 90Y-epratuzumab tetraxetan radioimmunotherapy in CD22+ Ph+ B-ALL: proof of principle.

Author: Chevallier P, Bodet-Milin C, Robillard N, Eugene T, Menard A, Le Houerou C, Guillaume T, Delaunay J, Escoffre-Barbe M, Wegener WA, Goldenberg DM, and Kraeber-Bodéré F
Subjects: Bone Marrow pathology, Female, Humans, Immunophenotyping, Middle Aged, Neoplasm, Residual diagnosis, Phenotype, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma metabolism, Remission Induction, Sialic Acid Binding Ig-like Lectin 2 metabolism, Treatment Outcome, Antibodies, Monoclonal, Humanized administration & dosage, Fusion Proteins, bcr-abl genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma radiotherapy, Radioimmunotherapy, Yttrium Radioisotopes therapeutic use
Abstract: Although targeted therapies are used increasingly in hematologic malignancies, we are unaware of any prior studies of radioimmunotherapy (RAIT) in B-acute lymphoblastic leukemia (ALL), even though this radiosensitive tumor expresses CD22, potentially a good target for this approach. Here, we report a patient with Philadelphia chromosome-positive B-ALL in third relapse who received RAIT with (90) yttrium ((90) Y)-labeled anti-CD22 epratuzumab tetraxetan. Seven weeks after initiating therapy, the patient achieved a BCR-ABL1 molecular remission documented by RT-qPCR, which is now continuing at 6 months while awaiting an allogeneic hematopoietic stem cell transplant. (90) Y-Epratuzumab tetraxetan may be a promising therapeutic option for CD22(+) B-ALL patients., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Published: 2013
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39. Prognostic impact of immune status and hematopoietic recovery before and after fludarabine, IV busulfan, and antithymocyte globulins (FB2 regimen) reduced-intensity conditioning regimen (RIC) allogeneic stem cell transplantation (allo-SCT).

Author: Le Bourgeois A, Lestang E, Guillaume T, Delaunay J, Ayari S, Blin N, Clavert A, Tessoulin B, Dubruille V, Mahe B, Roland V, Gastinne T, Le Gouill S, Moreau P, Mohty M, Planche L, and Chevallier P
Subjects: Adult, Aged, Antilymphocyte Serum pharmacology, Busulfan pharmacology, Disease-Free Survival, Female, Graft vs Host Disease prevention & control, Humans, Immunity, Innate drug effects, Leukemia immunology, Leukemia mortality, Lymphoma immunology, Lymphoma mortality, Male, Middle Aged, Multiple Myeloma immunology, Multiple Myeloma mortality, Myeloablative Agonists pharmacology, Recovery of Function immunology, Retrospective Studies, Transplantation, Homologous, Vidarabine pharmacology, Vidarabine therapeutic use, Antilymphocyte Serum therapeutic use, Busulfan therapeutic use, Hematopoietic Stem Cell Transplantation, Leukemia therapy, Lymphoma therapy, Multiple Myeloma therapy, Myeloablative Agonists therapeutic use, Transplantation Conditioning methods, Vidarabine analogs & derivatives
Abstract: This retrospective analysis aimed to assess hematopoietic and immune recovery in a cohort of 53 patients [males: n = 33; median age: 59 yr (range: 22-70)] who received a FB2 (fludarabine 120-150 mg/m² + IV busulfan 6.4 mg/kg + antithymocyte globulin thymoglobulin 5 mg/kg) reduced-intensity conditioning (RIC) allo-stem cells transplantations (SCT). With a median follow-up of 19 months (range: 2-53), the 2-yr overall survival, disease-free survival (DFS), relapse incidence, and non-relapse mortality were 63%, 59.5%, 35%, and 6%, respectively. In univariate analysis, the factors correlated with a significantly higher 2-yr OS and DFS were a higher total circulating lymphocytes count at transplant (>730/mm(3) ; OS: 81% vs. 43%, P = 0.02; DFS: 73% vs. 45.5%, P = 0.03) and a higher recovery of leukocytes (>5300/mm(3) ) (2-yr OS: 81% vs. 44%, P = 0.007; 2-yr DFS: 72% vs. 46%, P = 0.08), neutrophils (>3200/mm(3) ) (2-yr OS: 76% vs. 50%, P = 0.03; 2-yr DFS: 67% vs. 52.0%, P = 0.1), and monocytes (>590/mm(3) ; 2-yr OS: 80% vs. 45%, P = 0.004; 2-yr DFS: 76% vs. 42%, P = 0.01) at day +30 post-transplant. In multivariate analysis, the only independent factors associated with a significantly higher OS and DFS were a better immune status at transplant (lymphocytes count >730/mm(3) ) and a higher monocytes count (>590/mm(3) ) at day +30 post-transplant. These results suggest that immune status and hematopoietic recovery before and after FB2 RIC allo-SCT can be significant predictors of outcome. This paves the way for future studies aiming to closely monitor the kinetics of immune recovery after RIC allo-SCT and to evaluate the impact of growth factors and other immunostimulatory cytokines in the setting of RIC allo-SCT., (© 2012 John Wiley & Sons A/S.)
Published: 2013
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40. Reduced-intensity conditioning allogeneic stem cell transplantation for relapsed/refractory mantle cell lymphoma: a multicenter experience.

Author: Le Gouill S, Kröger N, Dhedin N, Nagler A, Bouabdallah K, Yakoub-Agha I, Kanouni T, Bulabois CE, Tournilhac O, Buzyn A, Rio B, Moles MP, Shimoni A, Bacher U, Ocheni S, Milpied N, Harousseau JL, Moreau P, Leux C, and Mohty M
Subjects: Adult, Aged, Female, Humans, Male, Middle Aged, Recurrence, Retrospective Studies, Lymphoma, Mantle-Cell surgery, Stem Cell Transplantation, Transplantation Conditioning
Abstract: Background: Despite therapeutic approach that combines rituximab-containing chemotherapy, followed or not by autologous stem cell transplantation (auto-SCT), mantle cell lymphoma (MCL) patients experience relapses. Reduced-intensity conditioning allogeneic stem cell transplantation (RIC-allo-SCT) at time of relapse may represent an attractive strategy., Patients and Methods: We report a multicenter retrospective analysis. Seventy MCL patients underwent RIC-allo-SCT in 12 centers., Results: Median age at transplantation was 56 years and median time from diagnosis to transplantation was 44 months. The median number of previous therapies was 2 (range, 1-5) including autologous transplantation in 47 cases. At time of transplantation, 35 patients were in complete remission, 20 were in partial response and 15 in stable disease or progressive disease. The median follow-up for living patients was 24 months. The 2-year event-free survival (EFS) and overall survival (OS) rates were 50% and 53%, respectively. The 1- and 2-year transplant-related mortality rates were 22% and 32%, respectively. The statistical analysis demonstrated that disease status at transplantation was the only parameter influencing EFS and OS., Conclusions: These results suggest that RIC-allo-SCT may be an effective therapy in MCL patients with a chemo-sensitive disease at time of transplantation, irrespective of the number of lines of prior therapy. Studies are warranted to investigate the best type of RIC regimen.
Published: 2012
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41. Clofarabine-containing conditioning regimen for allo-SCT in AML/ALL patients: a survey from the Acute Leukemia Working Party of EBMT.

Author: Chevallier P, Labopin M, Buchholz S, Ganser A, Ciceri F, Lioure B, Faul C, Guillerm G, Finke J, Huynh A, Schubert J, Kolb HJ, Polge E, Nagler A, and Mohty M
Subjects: Adolescent, Adult, Aged, Clofarabine, Female, Humans, Male, Middle Aged, Retrospective Studies, Young Adult, Adenine Nucleotides administration & dosage, Arabinonucleosides administration & dosage, Leukemia, Myeloid, Acute surgery, Precursor Cell Lymphoblastic Leukemia-Lymphoma surgery, Stem Cell Transplantation, Transplantation Conditioning
Abstract: Clofarabine (CLO), a second-generation purine analogue, has demonstrated an efficient anti-leukemia activity while showing a favorable toxicity profile. This retrospective multicenter report assessed the outcome of 90 patients who received a CLO-containing conditioning regimen before allo-SCT for AML (n = 69) or ALL (n = 21). Median age was 42 yr at transplant. The majority of cases (n = 66) presented with an active disease at transplant while 38 patients had received previous transplantation(s). A total of 88 and two patients received a reduced-intensity conditioning or a myeloablative regimen, respectively. Engraftment was achieved in 97% of evaluable patients. With a median follow-up of 14 months (range, 1-45), the 2-year OS, LFS, relapse, and NRM rates were 28 ± 5%, 23 ± 5%, 41 ± 6%, and 35 ± 5%, respectively. When comparing AML and ALL patients, OS and LFS were significantly higher for AML (OS, 35 ± 6% vs. 0%, P < 0.0001); LFS: 30 ± 6% vs. 0%, P < 0.0001). In a Cox multivariate analysis, an AML diagnosis was the only factor associated with a better LFS (HR = 0.37; 95%CI, 0.21-0.66; P = 0.001). We conclude that a CLO-containing conditioning regimen prior to allo-SCT might be an effective treatment. Prospective studies are needed to evaluate the potential role of CLO as part of conditioning regimens in acute leukemias., (© 2012 John Wiley & Sons A/S.)
Published: 2012
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42. Plerixafor for autologous peripheral blood stem cell mobilization in patients previously treated with fludarabine or lenalidomide.

Author: Malard F, Kröger N, Gabriel IH, Hübel K, Apperley JF, Basak GW, Douglas KW, Geraldes C, Jaksic O, Koristek Z, Lanza F, Lemoli R, Mikala G, Selleslag D, Worel N, Mohty M, and Duarte RF
Subjects: Adult, Aged, Anti-HIV Agents adverse effects, Antigens, CD34 blood, Antineoplastic Agents adverse effects, Benzylamines, Compassionate Use Trials, Cyclams, Female, Granulocyte Colony-Stimulating Factor administration & dosage, Granulocyte Colony-Stimulating Factor adverse effects, Heterocyclic Compounds adverse effects, Humans, Lenalidomide, Lymphoma, Non-Hodgkin blood, Male, Middle Aged, Multiple Myeloma blood, Thalidomide administration & dosage, Thalidomide adverse effects, Time Factors, Transplantation, Autologous, Vidarabine administration & dosage, Vidarabine adverse effects, Anti-HIV Agents administration & dosage, Antineoplastic Agents administration & dosage, Hematopoietic Stem Cell Mobilization methods, Heterocyclic Compounds administration & dosage, Lymphoma, Non-Hodgkin therapy, Multiple Myeloma therapy, Peripheral Blood Stem Cell Transplantation, Thalidomide analogs & derivatives, Vidarabine analogs & derivatives
Abstract: Fludarabine and lenalidomide are essential drugs in the front-line treatment of non-Hodgkin lymphoma (NHL) and multiple myeloma (MM), respectively. Data suggests that fludarabine and lenalidomide therapy may have a deleterious effect on stem cell mobilization. In the European compassionate use program, 48 patients (median age 57 years) previously treated with fludarabine (median 5 cycles; range: 1-7 cycles) were given plerixafor plus granulocyte colony-stimulating factor (G-CSF) for remobilization following a primary mobilization attempt. The overall median number of CD34+ cells collected was 2.3 × 10(6)/kg (range: 0.3-13.4). The minimum required number of CD34+ cells (≥2.0 × 10(6)/kg) was collected from 58% of patients in a median of 2 days. Thirty-five patients (median age = 57 years) previously treated with lenalidomide (median 5 cycles; range: 1-10 cycles) were given plerixafor plus G-CSF for remobilization. The overall median number of CD34+ cells collected was 3.4 × 10(6)/kg (range: 1.1-14.8). The minimum required number of CD34+ cells (≥2.0 × 10(6) per kg) was collected from 69% of patients in a median of 2 days. In conclusion, salvage mobilization with plerixafor plus G-CSF is successful in the majority of patients with MM previously treated with lenalidomide. In fludarabine-exposed patients, only 58% of patients will achieve successful salvage mobilization with plerixafor plus G-CSF, suggesting the need for novel mobilization regimens algorithms in this subgroup of patients., (Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)
Published: 2012
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