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Multiple Myeloma

Comparison of outcomes after unrelated cord blood and unmanipulated haploidentical stem cell transplantation in adults with acute leukemia

Leukemia volume 29, pages 18911900 (2015) | Download Citation

Abstract

Outcomes after unmanipulated haploidentical stem cell transplantation (Haplo) and after unrelated cord blood transplantation (UCBT) are encouraging and have become alternative options to treat patients with high-risk acute leukemia without human leukocyte antigen (HLA) matched donor. We compared outcomes after UCBT and Haplo in adults with de novo acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Median follow-up was 24 months. Analysis was performed separately for patients with AML, n=918 (Haplo=360, UCBT=558) and ALL, n=528 (Haplo=158 and UCBT=370). UCBT was associated with delayed engraftment and higher graft failure in both AML and ALL recipients. In multivariate analysis, UCBT was associated with lower incidence of chronic graft-vs-host disease both in the AML group (hazard ratio (HR)=0.63, P=0.008) and in the ALL group (HR=0.58, P=0.01). Not statistically significant differences were observed between Haplo and UCBT for relapse incidence (HR=0.95, P=0.76 for AML and HR=0.82, P=0.31 for ALL), non-relapse mortality (HR=1.16, P=0.47 for AML and HR=1.23, P=0.23 for ALL) and leukemia-free survival (HR 0.78, P=0.78 for AML and HR=1.00, P=0.84 for ALL). There were no statistically differences on main outcomes after unmanipulated Haplo and UCBT, and both approaches are valid for acute leukemia patients lacking a HLA matched donor. Both strategies expand the donor pool for patients in need.

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Acknowledgements

The authors thank Chantal Kenzey for helping with data collection and the association ‘Cordons de vie’, Monaco. VR is funded of National Institute Health Research (NIHR)-Biomedical Research Centre (BRC) funding scheme. Professor Noel Milpied, CHU Bordeaux, Pessac, France; Professor JJ Cornelissen, Erasmus MC-Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands; Professor Ihsan Karadogan, Stem Cell Transplant Unit, Medical Park Hospitals, Antalya, Turkey; Professor Patrice Chevallier, Department of D'Hematologie, CHU Nantes, Nantes, France; Professor Mohamad Mohty, Hopital Saint Antoine, Paris, France; Professor E Deconinck, Service d'Hématologie, Hopital Jean Minjoz, Besancon, France; Professor Boris Afanasyev, SPb State I. Pavlov Medical University, St Petersburg, Russia; Professor Johanna Tischer, Klinikum Grosshadern, Munich, Germany; Professor Gérard Socié, Department of Hematology-BMT, Hopital St Louis, Paris, France; Professor P-S Rohrlich, Hôpital de l'ARCHET I, Nice, France; Professor Alessandro Rambaldi, Azienda Ospedaliera Papa Giovanni XXIII-Hematology and Bone Marrow Transplant Unit, Bergamo, Italy; Professor G Bandini, Bologna University, S Orsola-Malpighi Hospital, Bologna, Italy; Professor B Kremens, Department of Bone Marrow Transplantation, University Hospital, Essen, Germany; Professor Z Gülbas, Bone Marrow Transplantation Department, Anadolu Medical Center Hospital, Kocaeli, Turkey; Professor GF Mufti, Department of Haematological Medicine, GKT School of Medicine, London, UK; Professor Menachem Bitan, Tel-Aviv University, Tel-Hashomer, Israel; Professor I Yakoub-Agha, Hôpital Huriez, UAM allo-CSH, CHRU, Lille, France; Professor C Tarella, Azienda Ospedaliera S Giovanni, Torino, Italy; Professor E Petersen, University Medical Centre, Utrecht, The Netherlands; Professor H Greinix, Medical University Graz, Graz, Austria; Professor J-M Ribera Santasusana, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain; Professor G Gunhan, Adult Stem Cell Transplantation Unit, Department of Hematology, Ankara University Faculty of Medicine, Ankara, Turkey; Professor N Fegueux, Département d'Hématologie Clinique, CHU Lapeyronie, Montpellier, France; Professor Depei Wu, Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou, China; Professor A Ghavamzadeh, Hematology-Oncology and BMT Research, Shariati Hospital, Teheran, Iran; Professor J-Y Cahn, Hopital A Michallon, Hématologie Clinique, Pole Cancérologie, Grenoble, France; Professor C Cordonnier, Hôpital Henri Mondor, Creteil, France; Professor J-O Bay, Fédération de Greffe de Moelle et de, Clermont-Ferrand, France; Professor I Majolino, Ospedale S Camillo-Forlanini, Rome, Italy; Professor G Irrera, Azienda Ospedaliera, Reggio Calabria, Italy; Professor M Potter, Royal Marsden Hospital, London, UK; Hôpital Nord, Saint Etienne Cedex 2, France; Professor F Guilhot, Hopital La Miletrie, Poitiers, France; Professor Paul Cannell, RP Group Royal Perth Hospital, Perth, Australia; Professor I Heras, Hospital Morales Meseguer, Murcia, Spain; Professor A Olivieri, Azienda Ospedali Riuniti di Ancona, Ancona-Torrete, Italy; Professor G Ehninger, Universitaetsklinikum Dresden, Dresden, Germany; Professor J Passweg, University Hospital, Basel, Switzerland; Professor O Reman, Centre Hospitalier Universitaire, Caen, France; Professor J Cornish, Bristol Royal Hospital for Children, Bristol, UK; Professor C Craddock, Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK; Professor M-J Pascual Cascon, Hospital Carlos Haya, Málaga, Spain; Professor R Fanin, University Hospital, Udine, Italy; Professor H Einsele, Allogeneic Stem Cell Transplant Center, Würzburg, Germany; Professor K Thomson, University College London Hospital, London, UK; Professor P Gomez Garcia, Hospital Reina Sofia, Córdoba, Spain; Professor BE Gibson, Glasgow Royal Infirmary, Glasgow, UK; Professor C Solano, Hospital Clínico Universitario, Valencia, Spain; Professor M Jurado Chacon, Hospital University Virgen de las Nieves, Granada, Spain; Professor L Clement, Unit de Transplantation Médullaire, Vandoeuvre Les Nancy, France; Professor NH Russell, Nottingham City Hospital, Nottingham, UK; Professor J-L Diez-Martin, Hospital Gregorio Marañón, Madrid, Spain; Professor Mair Pedro de Souza, Hospital Amaral Carvalho, Jau, Brazil; Professor D Bunjes, Medizinische Klinik und Poliklinik, Ulm, Germany; Professor Montserrat Rovira, Hospital Clinic, Barcelona, Spain; Professor Reuven Or, Hadassah University Hospital, Jerusalem, Israel; Professor S Nguyen, Hopital Pitie-Salpetriere, Paris, France; Professor P Pioltelli, Ospedale San Gerardo, Monza, Italy; Professor M Grasso, Az Ospedaliera S Croce e Carle, Cuneo, Italy; Professor N Ifrah, CHRU, Service des Maladies du Sang, Angers, France; Professor G Guillerm, CHU Morvan, Brest, France; Professor T Lamy, Centre Hospitalier Universitaire de Rennes, Rennes, France; Professor W Rösler, University Hospital Erlangen, Erlangen, Germany; Professor F Jardin, Centre Henri Becquerel, Rouen, France; Professor U Schanz, University Hospital, Zürich, Switzerland; Professor J Maertens, University Hospital Gasthuisberg, Leuven, Belgium; Professor Y Bertrand, Hôpital E Herriot, Lyon, France; Professor O Ringden, Department of Hematology, Karolinska University Hospital, Huddinge, Sweden; Professor M Zecca, Policlinico San Matteo, Pavia, Italy; Professor G Martinelli, European Institute of Oncology, Milano, Italy; Professor R Scime, Ospedale V Cervello, Palermo, Italy; Professor M Yeshurun, Beilinson Hospital, Petach-Tikva, Israel; Professor J-S Kühl, Charité, Campus Benjamin Franklin, Berlin, Germany; Professor X Poiré, University Hospital VUB, Brussels, Belgium; Professor T de Revel, Hôpital Percy, Clamart, France; Professor JH Veelken, Leiden University Hospital, Leiden, The Netherlands; Professor Jane Apperley, Imperial College, London, UK; Professor P Kalhs, Medizinische Universitaet Wien, Vienna, Austria; Professor T Zuckerman, Department of Hematology, Rambam Health Care Campus, Haifa, Israel; Professor L Castagna, Istituto Clinico Humanitas, Milano, Italy; Professor M Aljurf, Oncology (Section of Adult Haematolgy/BMT), King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; Professor A Anagnostopoulos, Haematology Department/BMT Unit, George Papanicolaou General Hospital, Thessaloniki, Greece; Professor E Tholouli, Manchester Royal Infirmary, Manchester, UK; Professor N Kröger, Department of Stem cell Transplantation, University Hospital Eppendorf, Hamburg, Germany; Professor Bourhis, BMT Service, Division of Hematology, Department of Medical Oncology, Gustave Roussy, Institut de Cancérologie, Villejuif, France; Professor Y Beguin, University of Liege, Liege, Belgium; Professor D Caballero, Hospital Clínico, Salamanca, Spain; Professor C Favre, Unità Operativa Oncoematologia Pediatrica, Pisa, Italy; Professor C Schmid, Klinikum Augsburg, II Medizinische Klinik, Augsburg, Germany; Professor L Cavanna, Hospital Guglielmo da Saliceto, Piacenza, Italy; Professor A Peniket, Department of Haematology, Oxford, UK; Professor Y Chalandon, Hopitaux Universitaires de Geneve, Geneva, Switzerland; Professor R Cairoli, Ospedale di Niguarda Ca' Granda, Milano, Italy; Professor G Saglio, University of Torino, Torino, Italy; Professor S Sica, Universita Cattolica S Cuore, Rome, Italy; Professor P Dreger, University of Heidelberg, Medizinische Klinik u Poliklinik V, Heidelberg, Germany; Professor C Peschel, Klinkum Rechts der Isar, Munich, Germany; Professor J Sanchez de Toledo, Hospital Vall d'Hebron, Barcelona, Spain; Professor J Clausen, Elisabethinen-Hospital, Linz, Austria; Professor A Huynh, CHU de Toulouse Department of Hematologie, Hopital Purpan, Toulouse, France; Professor K Schäfer-Eckart, Klinikum Nürnberg, Nürnberg, Germany; Professor D Deeren, Hematology and Oncology Department; Heilig Hartziekenhuis, Roeselare, Belgium; Professor G Specchia, Universita degli Studi di Bari, Bari, Italy; Professor B Lioure, CHU Hautepierre, Service d'Onco Hematologie, Strasbourg, France; Professor A Wahlin, Umea University Hospital, Umeå, Sweden; Professor LA Noens, University Hospital Gent, Gent, Belgium; Professor I Espigado, Hospital 'Virgen del Rocio', Sevilla, Spain; Professor E Holler, University Regensburg, Regensburg, Germany; Professor E Angelucci, Ospedale A Businco, Cagliari, Italy; PO 'R Binaghi', Cagliari, Italy; Professor D Bordessoule, CHRU Limoges, Limoges, France; Professor P Galieni, Mazzoni Hospital, Ascoli Piceno, Italy; Professor O Hermine, Hôpital Necker, Paris, France; Professor G Sucak, Gazi Universitesi Tip Fakültesi, Ankara, Turkey; Professor T Gedde-Dahl, Department of Medicine, Rikshospitalet, The National Hospital, Oslo, Norway; Professor C Richard Espiga, Hospital U Marqués de Valdecilla, Santander, Spain; Professor K Carlson, University Hospital, Uppsala, Sweden; Professor M Nikolousis, Birmingham Heartlands Hospital, Birmingham, UK; Professor M Brune, Sahlgrenska University Hospital, Goeteborg, Sweden; Professor C Kratz, Hannover Medical University, Hannover, Germany; Professor P Mazza, Ospedale Nord, Taranto, Italy; Professor D Konstantinov, Specialized Children’s Oncohematology Hospital, Sofia, Bulgaria; Professor D Niederwieser, University Hospital Leipzig, Leipzig, Germany; Professor G Kobbe, Heinrich Heine Universität, Düsseldorf, Germany; Professor K Vettenranta, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland; Professor M Hallek, Department of Medicine, University of Cologne-I, Cologne, Germany; Professor J-L Bello Lopez, Hospital Clinico Universitario, Santiago De Compostela, Spain; Professor F Abdel-Rahman, King Hussein Cancer Centre, Amman, Jordan; Professor H Ozdogu, Baskent University Hospital, Adana, Turkey; Professor J Lopez-Jimenez, Hospital Ramon y Cajal, Madrid, Spain; Professor A Unal, Department of Hematology and Oncology, Erciyes Medical School, Kayseri, Turkey; Professor S Zver, University Medical Center, Ljubljana, Slovenia; Professor AE Hunter, Leicester Royal Infirmary, Leicester, UK; Professor A Sampol, Hospital Universitario Son Espases, Palma De Mallorca, Spain; ICO – Professor R Duarte Palomino, Hospital Duran i Reynals, Barcelona, Spain; Professor H Campbell, Royal Liverpool Children’s NHS Trust, Liverpool, UK; Professor J Snowden, North Trent BMT Programme (Adults), Sheffield, UK; Professor G Storti, A.O.R.N. 'San.G Moscati', Avellino, Italy; Professor A Velardi, Sezione di Ematologia, Dipartimento di Medicina Clinica e Sperimentale, Università di Perugia; Ospedale Santa Maria della Misericordia, Perugia, Italy; Professor W Wiktor-Jedrzejczak, Central Clinical Hospital, Warsaw, Poland; Professor D Russo, AZ. Spedali Civili- Brescia Universitu of Brescia, Brescia, Italy; Professor G Cardinale, A.R.N.A.S. Civico, Di Cristina, U.O. Ematologia, Palermo, Italy; Professor R Ram, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Professor Z Bolaman, Adnan Menderes University Medical Faculty, Aydin, Turkey; Professor G Michel, Hopital d'Enfants de la Timone, CHU Département Hématologie Oncologie Pédiatrique, Marseille, France; Professor L Kanz, Universität Tübingen, Tübingen, Germany; Professor X Poiré, Cliniques Universitaires St Luc, Brussels, Belgium; Professor M Gramatzki, Division of Stem Cell Transplantation and Immunotherapy, Kiel, Germany; Professor MN Chonghaile, St James Hospital Trinity College, Dublin, Ireland; Professor A Campos, Institute of Portugues de Oncologia do Porto, Porto, Portugal; Professor H Martin, Goethe-Universität, Frankfurt am Main, Germany; Professor M Casini, Hospital San Maurizio, Bolzano, Italy; Professor G Stuhler, Deutsche Klinik für Diagnostik, KMT Zentrum, Wiesbaden, Germany; Professor G Marotta, Policlinico Le Scotte, Siena, Italy; Professor J Moraleda, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain; Professor H Bittencourt, Ste-Justine Hospital, Montréal, Canada; Professor R Salim, Royal Liverpool University Hospital, Liverpool, UK; Professor D Selleslag, A.Z. Sint-Jan, Brugge, Belgium; Professor N Cascavilla, IRCCS, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; Professor G Visani, Pesaro Hospital, Pesaro, Italy; Professor A Lange, DCTK, Wroclaw, Poland; Professor T Masszi, Department of Haematology and Stem Cell Transplant, Budapest, Hungary; Professor D Stamatovic, Military Medical Academy, Belgrade, Serbia and Montenegro; Professor Dr Axel A Fauser, Klinik für Knochenmark Transplantation, Hämatologie und Onkologie, Idar-Oberstein, Germany; Professor C Vallejo Llamas, Hospital Aranzazu, San Sebastian, Spain; Hospital Ampang, Ampang, Malaysia; Professor P Corradini, University of Milano, Milano, Italy; Professor F Benedetti, Policlinico G.B. Rossi, Verona, Italy; Professor K Theunissen, Virga Jesse Hospital, Hasselt, Belgium; Professor S Gonzalez Muniz, Hospital Covadonga, Oviedo, Spain; Professor V Pavone, Hospital C Panico, Tricase (Lecce), Italy; Professor A Vitek, Institute of Hematology and Blood Transfusion, Prague, Czech Republic; Professor C Bokemeyer, Universitätsklinikum Hamburg-Eppendorf, Onkologisches Zentrum, II. Medizinische Klinik und Poliklinik, Hamburg, Germany; Professor M Musso Ospedale La Maddalena, Department of Oncologico, Palermo, Italy; Professor T O’Brien, Sydney Children’s Hospital, Randwick, Australia; Professor P Shaw, The Children’s Hospital at Westmead, Sydney, Australia; Professor A Sandstedt, University Hospital, Linköping, Sweden; Professor G de Rosa, Division of Hematology, Federico II' Medical School, University of Napoli, Napoli, Italy; Professor J Gribben, St Bartholomew’s and The Royal London Hospital, London, UK; Professor J Finke, Department of Medicine-Hematology, Oncology, University of Freiburg, Freiburg, Germany; Professor F Salvi, H SS. Antonio e Biagio, Alessandria, Italy; Professor L Fouillard, Centre Hospitalier de Meaux, Haematology, Meaux, France; Professor H Tilly, Pédiatrie et Génétique Médicale, Rouen, France.

Author Contributions

AR, EG, VR, FC and MM designed the study, AR prepared and analyzed data, AR wrote the paper, AR and ML, performed the statistical analysis, GS, WA, AB, DB, AB, HH, DK, YK, MM, AP, JS, SS, HS, JS, LV and AN provided cases for the study, SP and FV helped with data and manuscript preparation. All the authors edited and approved the manuscript.

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Affiliations

  1. Hôpital Saint Antoine, Service d’Hématologie et Thérapie Cellulaire, AP-HP, Paris, France

    • A Ruggeri
    • , M Labopin
    •  & M Mohty
  2. INSERM, UMRs 938, Paris, France

    • A Ruggeri
    •  & M Mohty
  3. Hôpital Saint Louis, Eurocord, IUH University Paris VII, Paris, France

    • A Ruggeri
    • , F Volt
    • , E Gluckman
    •  & V Rocha
  4. Hôpital Saint Antoine, Université Pierre and Marie Curie, Paris, France

    • M Labopin
    •  & M Mohty
  5. Hospital Universitario y Politécnico La Fe, Valencia, Spain

    • G Sanz
    •  & J Sanz
  6. Hematology and BMT Unit, San Raffaele Scientific Institute, Milano, Italy

    • S Piemontese
    •  & F Ciceri
  7. Rome Transplant Network, University Tor Vergata, Rome, Italy

    • W Arcese
    •  & A Picardi
  8. Dipartimento di Ematologia, Ospedale San Martino, Genova, Italy

    • A Bacigalupo
  9. Institut Paoli Calmettes, Marseille, France

    • D Blaise
  10. Careggi University Hospital, Firenze, Italy

    • A Bosi
  11. Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

    • H Huang
  12. Evangelismos Hospital, Division of Hematology, BMT Unit, Athens, Greece

    • D Karakasis
  13. Stem Cell Transplant Unit, Medical Park, Antalya, Turkey

    • Y Koc
  14. Hôpital Edouard Herriot, Lyon, France

    • M Michallet
  15. Ospedale Civile, Dipartimento di Ematologia, BMT Unit, Pescara, Italy

    • S Santarone
  16. Rigshospitalet, Copenhagen, Denmark

    • H Sengelov
  17. Hospital Santa Creu i Sant Pau, Jose Carreras Institute, Universitat Autonoma de Barcelona, Barcelona, Spain

    • J Sierra
  18. CHU Montpellier, Montpellier, France

    • L Vincent
  19. Chaim Sheba Medical Center, Tel-Hashomer, Israel

    • A Nagler
  20. ALWP Office Hôpital Saint Antoine, Service d’Hématologie et Thérapie Cellulaire, AP-HP, Paris, France

    • A Nagler
  21. Monacord, Centre Scientifique de Monaco, Monaco, France

    • E Gluckman
  22. Churchill Hospital, Oxford University, Oxford, UK

    • V Rocha

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Correspondence to A Ruggeri.

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