Abstract
Even with the availability of targeted drugs, allogeneic hematopoietic cell transplantation (allo-HCT) is the only therapy with curative potential for patients with CLL. Cure can be assessed by comparing long-term survival of patients to the matched general population. Using data from 2589 patients who received allo-HCT between 2000 and 2010, we used landmark analyses and methods from relative survival analysis to calculate excess mortality compared with an age-, sex- and calendar year-matched general population. Estimated event-free survival, overall survival and non-relapse mortality (NRM) 10 years after allo-HCT were 28% (95% confidence interval (CI), 25–31), 35% (95% CI, 32–38) and 40% (95% CI, 37–42), respectively. Patients who passed the 5-year landmark event-free survival (N=394) had a 79% probability (95% CI, 73–85) of surviving the subsequent 5 years without an event. Relapse and NRM contributed equally to treatment failure. Five-year mortality for 45- and 65-year-old reference patients who were event-free at the 5-year landmark was 8% and 47% compared with 3% and 14% in the matched general population, respectively. The prospect of long-term disease-free survival remains an argument to consider allo-HCT for young patients with high-risk CLL, and programs to understand and prevent late causes of failure for long-term survivors are warranted, especially for older patients.
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Acknowledgements
We thank Maja Pohar Perme (Institute for Biostatistics and Medical Informatics, University of Ljubljana, Ljubljana, Slovenia) for help with the software. Further, we are very grateful to Emili Montserrat who gave substantial input and critically revised the manuscript.
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Gerhard Ehninger, Universitaetsklinikum Dresden, Dresden, Germany; Dietger Niederwieser, University Hospital Leipzig, Leipzig, Germany; Pavel Jindra, Charles University Hospital, Pilsen, Czech Republic; Henrik Sengeloev, Rigshospitalet, Copenhagen, Denmark; Martin Gramatzki, University Hospital Schleswig-Holstein Kiel Campus, Kiel, Germany; Peter Dreger, University of Heidelberg, Heidelberg, Germany; Eefke Petersen, University Medical Centre, Utrecht, The Netherlands; Donald Bunjes, Universitätsklinikum Ulm, Ulm, Germany; Michael Potter, Royal Marsden Hospital, London, UK; Dietrich Beelen, University Hospital, Essen, Germany; Jan Cornelissen, Erasmus MC-Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands; Ibrahim Yakoub-Agha, Hôpital HURIEZ, Lille, FranceNigel Russell, Nottingham City Hospital, Nottingham, UK; Jürgen Finke, University of Freiburg, Freiburg, Germany; Hélène Schoemans, University Hospital Gasthuisberg, Leuven, Belgium; Antonin Vitek, Institute of Hematology and Blood Transfusion, Prague, Czech Republic; Alvaro Urbano Ispizua, Hospital Clinic, Barcelona, Spain; Didier Blaise, Institut Paoli Calmettes, Marseille, FranceLiisa Volin, HUCH Comprehensive Cancer Center, Helsinki, Finland; Renate Arnold, Charité Universitätsmedizin Berlin, Berlin, Germany; Patrice Chevallier, CHU Nantes, Nantes, France; Dolores Caballero, Hospital Clínico, Salamanca, Spain; Joan Hendrik Veelken, Leiden University Hospital, Leiden, The Netherlands; Ghulam Mufti, GKT School of Medicine, London, UK; Noel Milpied, Hôpital Haut-leveque, Pessac, France; Bruno Benedetto, AOU Citta della Salute e della Scienza di Torino, Torino, Italy; Michel Schaap, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands; Véronique Leblond, Universite Paris IV, Hopital la Pitié-Salpêtrière, Paris, France; Manos Nikolousis, Birmingham Heartlands Hospital, Birmingham, UK; Michael Hallek, University of Cologne, Cologne, Germany; Jakob Passweg, University Hospital, Basel, Switzerland; Per Ljungman, Karolinska University Hospital, Stockholm, Sweden; Tamás Masszi, St István and St Laszlo Hospital, Budapest, Hungary; Matthias Stelljes, University of Münster, Münster, Germany; Paul Browne, St James's Hospital, Dublin, Ireland; Bertram Glass, Asklepios Klinik St Georg, Hamburg, Germany; Carlos Richard Espiga, Hospital U Marqués de Valdecilla, Santander, Spain; Jean Henri Bourhis, Gustave Roussy, Institut de Cancérologie, Villejuif, France; John Gribben, St Bartholomew's and The Royal London NHS Trust, London, UK; Roberto Foa, Univ. 'La Sapienza', Rome, ItalyJorge Sierra, Hospital Santa Creu i Sant Pau, Barcelona, Spain; Jiri Mayer, University Hospital Brno, Brno, Czech Republic; Mauricette Michallet, Centre Hospitalier Lyon Sud, Lyon, France; Kirsty Thomson, University College London Hospital, London, UK; Ellen Meijer, VU University Medical Center, Amsterdam, The Netherlands; Wolfgang Blau, Universitaetsmedizin Berlin, Berlin, Germany; Ernst Holler, University Regensburg, Regensburg, Germany; Andrea Bacigalupo, Ospedale San Martino, Genova, Italy; Francois Guilhot, Hopital La Miletrie, Poitiers, France; Kristina Carlson, University Hospital, Uppsala, Sweden; Pierre Zachée, ZNA, Antwerp, Belgium; Norbert Ifrah, CHRU, Angers, France; José Rafael Cabrera Marín, Hospital Universitario Puerta de Hierro, Madrid, Spain; Gerard Socié, Hopital St Louis, Paris, France; Grant McQuaker, Gartnaval General Hospital, Glasgow, UK; Agostino Cortelezzi, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, Italy; Stig Lenhoff, Skanes University Hospital, Lund, Sweden; Johanna Tischer, Klinikum Grosshadern, Munich, Germany; Giuseppe Irrera, Azienda Ospedaliera, Reggio Calabria, Italy; Renato Fanin, Azienda Ospedaliero Universitaria di Udine, Udine, ItalyYves Beguin, CHU Sart-Tilman, Liege, Belgium; Arnon Nagler, Chaim Sheba Medical Center, Tel-Hashomer, Israel; Stephen Mackinnon, Royal Free Hospital and School of Medicine, London, UK; Maija Itälä-Remes, Turku University, Turku, FinlandEric Deconinck, Hopital Jean Minjoz, Besancon, France; Gerald Wulf, Universitätsklinikum Göttingen, Gottingen, Germany; Paolo Corradini, University of Milano, Milano, Italy; Maria Gilleece, Bexley Wing, St James's Institute of Oncology, Leeds, UK; Andy Peniket, Churchill Hospital, Oxford, UK; Arnold Ganser, Hannover Medical School, Hannover, Germany; Gernot Stuhler, Deutsche Klinik für Diagnostik, Wiesbaden, Germany; Edgar Faber, University Hospital, Olomouc, Czech Republic; Michal Komarnicki, Poznan University of Medical Sciences, Poznan, Poland; Lothar Kanz, Universität Tübingen, Tübingen, Germany; Mats Brune, Sahlgrenska University Hospital, Gothenburg, Sweden; Nicolaus Kröger, University Hospital Eppendorf, Hamburg, Germany; Thierry Lamy, Centre Hospitalier Universitaire de Rennes, Rennes, France; Miguel Sanz, Hospital Universitario La Fe, Valencia, Spain; Slawomira Kyrcz-Krzemien, Medical University of Silesia, Katowice, Poland; Kim Orchard, Southampton General Hospital, Southampton, UK; Ann Hunter, Leicester Royal Infirmary, Leicester, UKAnna Sandstedt, University Hospital, Linköping, Sweden; Nathalie Fegueux, CHU Lapeyronie, Montpellier, France; Giuseppe Bandini, Bologna University, S Orsola-Malpighi Hospital, Bologna, Italy; Stephen Robinson, Bristol Royal Hospital for Children, Bristol, UK; Charles Craddock, Queen Elizabeth Hospital, Birmingham, UK; Charles Crawley, Addenbrookes Hospital, Cambridge, UK; Laimonas Griskevicius, Vilnius University Hospital Santariskiu Klinikos, Vilnius, Lithuania; Adrian Bloor, Christie NHS Trust Hospital, Manchester, UK; Oumédaly Reman, CHU CAEN, Caen, France; Inken Hilgendorf, Universitätsklinikum Jena, Jena, Germany; Paul Cannell, Fiona Stanley Hospital, Perth Western Australia, Australia; Fabio Ciceri, Ospedale San Raffaele srl, Milano, Italy; Peter Kalhs, Medizinische Universitaet Wien, Vienna, Austria; Simona Sica, Universita Cattolica S Cuore, Rome, Italy; Hildegard Greinix, LKH - University Hospital Graz, Graz, AustriaRosanna Scimè, Ospedale V. Cervello, Palermo, Italy; Dominik Selleslag, AZ Sint-Jan, Brugge, Belgium; William Krüger, Klinik für Innere Medizin C, Greifswald, Germany; Anne Huynh, Institut Universitaire du Cancer Toulouse, Toulouse, France; Herman Einsele, Universitätsklinikum Würzburg, Würzburg, Germany; Jörg Bittenbring, University of Saarland, Homburg, Germany; Attilio Olivieri, Azienda Ospedali Riuniti di Ancona, Ancona, Italy; Olivier Hermine, Hôpital Necker, Paris, FranceTobias Gedde-Dahl, Rikshospitalet, Oslo, Norway; Jozsef Zsiros, Emma Kinderziekenhuis, Amsterdam, The Netherlands; Dennis Guyotat, CHRU St Etienne, Saint Etienne, FranceCatherine Cordonnier, Hôpital Henri Mondor, Creteil, FranceAntonio Campos, Inst. Português de Oncologia do Porto, Porto, PortugalMarco Casini, Hospital San Maurizio, Bolzano, Italy; Giovanni Martinelli, European Institute of Oncology, Milano, ItalyLutz Peter Müller, Martin-Luther-Universität Halle-Wittenberg, Halle, Germany; Gustaaf van Imhoff, University Medical Center Groningen (UMCG), Groningen, The Netherlands; Andreas Neubauer, University Hospital Giessen and Marburg, Marburg, Germany; Bruno Lioure, Nouvel Hopital Civil, Strasbourg, France; Rose-Marie Hamladji, Centre Pierre et Marie Curie, Alger, Algeria; Lucien Noens, University Hospital Gent, Ghent, Belgium; Matthias Theobald, University Medical Center Mainz, Mainz, Germany; Flavia Salvi, H SS. Antonio e Biagio, Alessandria, Italy; Ron Ram, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Xavier Poiré, Cliniques Universitaires St Luc, Brussels, Belgium; Reuven Or, Hadassah University Hospital, Jerusalem, IsraelYves Chalandon, Hôpitaux Universitaires de Genève, Geneva, Switzerland; Carlos Solano, Hospital Clínico Universitario, Valencia, Spain; Keith Wilson, University Hospital of Wales, Cardiff, Wales, UK; Josep Maria Ribera Santasusana, ICO-Hospital Universitari Germans Trias i Pujol, Barcelona, Spain; Dimitrios Karakasis, Evangelismos Hospital, Athens, Greece; Kerstin Schäfer-Eckart, Klinikum Nürnberg, Nürnberg, Germany; Anders Wahlin, Umea University Hospital, Umeå, Sweden; Mohamad Mohty, Hospital Saint Antoine, Paris, France; Andrea Velardi, Ospedale Santa Maria della Misericordia, Perugia, Italy; Dominique Bron, Institut Jules Bordet, Brussels, Belgium; Adrián Alegre, Hospital de la Princesa, Madrid, Spain; Roberto Cairoli, Ospedale di Niguarda Ca' Granda, Milano, Italy; Giuseppe Marotta, Azienda Ospedaliera Universitaria Senese, Siena, Italy; Andrzej Lange, DCTK, Wroclaw, Poland; Franco Narni, Azienda Ospedaliero Universitaria di Modena Policlinico, Modena, Italy; Axel Fauser, Klinik für Knochenmarktransplantation, Idar-Oberstein, Germany; Alessandro Rambaldi, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy; Gaelle Guillerm, C.H.R.U de Brest, Brest, France; Inmaculada Heras, Hospital Morales Meseguer, Murcia, Spain; John Snowden, Royal Hallamshire Hospital, Sheffield, UK; Wieslaw Wiktor-Jedrzejczak, Central Clinical Hospital, Warsaw, Poland; Urs Schanz, University Hospital, Zürich, Switzerland; Jean Yves Cahn, Hopital A. Michallon, Grenoble, France; Manuel Abecasis, Inst. Portugues Oncologia, Lisboa, Portugal; Guido Kobbe, Heinrich Heine Universität, Düsseldorf, Germany; Rahuman Salim, Royal Liverpool University Hospital, Liverpool, UK; Christian Junghanss, Universität Rostock, Rostock, Germany; Erik Kay Segel, Arhus Amtssygehus, Aarhus, DenmarkL. Clement, Hopital d'Enfants, Vandoeuvre Les Nancy, France; Pavel Zák, Charles University Hospital, Hradec Králové, Czech Republic; Bernd Metzner, Klinikum Oldenburg, Oldenburg, Germany; Ildefonso Espigado, Hospital Universitario Virgen del Rocío, Sevilla, Spain; Herve Tilly, Centre Henri Becquerel, Rouen, France; Wilfried Schroyens, Antwerp University Hospital (UZA), Antwerp Edegem, Belgium; Claudio Favre, Azienda Ospedaliera Universitaria Pisa, Pisa, Italy; Domenico Russo, Azienda Ospedaliera Spedali Civili Di Brescia, Brescia, Italy; Günther Gastl, University Hospital Innsbruck, Innsbruck, Austria; Jacques-Olivier Bay, CHU ESTAING, Clermont-Ferrand, France; Emilio Paolo Alessandrino, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Ignazio Majolino, Ospedale S Camillo, Rome, Italy; Alberto Bosi, Ospedale di Careggi, Firenze, Italy; Tsila Zuckerman, Rambam Medical Center, Haifa, IsraelMahmoud Aljurf, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia; Jackie Thomson, Haematology Pretoria East Hospital, Pretoria Gauteng, South Africa; Pietro Pioltelli, Ospedale San Gerardo, Monza, Italy; Achilles Anagnostopoulos, George Papanicolaou General Hospital, Thessaloniki, GreeceHarry Schouten, University Hospital Maastricht, Maastricht, The Netherlands; Eleni Tholouli, Manchester Royal Infirmary, Manchester, UK; Gunhan Gurman, Ankara University Faculty of Medicine, Ankara, Turkey; Filiz Vural, Ege University Medical School, Izmir, Turkey; Samo Zver, University Medical Center, Ljubljana, Slovenia; Soledad González Muñiz, Hospital Universitario Central de Asturias, Asturias, Spain; Boris Afanasyev, Saint Petersburg State Medical Pavlov University, St Petersburg, Russia; David Pohlreich, Charles University Hospital, Prague, Czech Republic; Andrzej Hellmann, Medical University of Gdansk, Gdansk, Poland; Wolf Rösler, University Hospital Erlangen, Erlangen, Germany; Sonja Martin, Robert-Bosch-Krankenhaus, Stuttgart, Germany; Jane Apperley, Hammersmith Hospital, London, UK; Damian Finnegan, Belfast City Hospital, Belfast, Northern Ireland, UK; Marc Renaud, Hopital Bretonneau, Tours, France; Damir Nemet, University Hospital Center Rebro, Zagreb, Croatia; Dominic Culligan, Aberdeen Royal Infirmary – Foresterhill, Aberdeen, UK; Luca Castagna, Istituto Clinico Humanitas, Rozzano Milano, Italy; Nicola Cascavilla, IRCCS, Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy; Mickey Koh, St George's Hospital, London, UK; Manuel Jurado Chacón, Hospital Universitario Virgen de las Nieves, Granada, Spain; Hakan Ozdogu, Baskent University Hospital, Yuregir Adana, Turkey; Andrew Spencer, The Alfred Hospital, Melbourne, Australia; Carlos Vallejo Llamas, Hospital Universitario Donostia, San Sebastian Gipuzkoa, Spain; Mariella Grasso, Az. Ospedaliera S Croce e Carle, Cuneo, Italy; Sebastian Garzon Lopez, Hospital del SAS, Cádiz Jerez de la Frontera, Spain; Fabio Benedetti, Policlinico GB Rossi, Verona, Italy; Dries Deeren, AZ Delta, Roeselare, Belgium; Thierry de Revel, Hôpital d'instruction des armées Percy, Clamart, France; Maurizio Musso, Ospedale La Maddalena - Dpt. Oncologico, Palermo, Italy; Kazimierz Halaburda, Institute of Hematology and Transfusion Medicine, Warsaw, Poland; Anna Sureda, ICO-Hospital Duran i Reynals, Barcelona, Spain; Emanuele Angelucci, Ospedale 'A Businco' Cagliari, Cagliari, Italy; José Luis Diez-Martin, Hospital Gregorio Marañón, Madrid, Spain; Hannah Hunter, Derriford Hospital, Plymouth, UK; Yener Koc, Medical Park Hospitals, Antalya, Turkey; Dominique Bordessoule, CHRU Limoges, Limoges, France; Loic Fouillard, Centre Hospitalier de Meaux, Meaux, France; Paolo Di Bartolomeo, Ospedale Civile, Pescara, Italy; Patrizio Mazza, Ospedale Nord, Taranto, Italy; Nicolas Novitzky, University of Cape Town Faculty of Health Sciences, Cape Town, South Africa; Christian Peschel, Klinkum Rechts der Isar, Munich, Germany; Jose Luis Bello López, Complexo Hospitalario Universitario de Santiago (CHUS), Santiago De Compostela, Spain; Maria Jesús Pascual Cascon, Hospital Regional de Málaga, Málaga, Spain; Kenneth R. Romeril, Wellington Hospital, Wellington, New ZealandRik Schots, Universitair Zieken; huis Brussel, Brussels, Belgium; Pirjo Koistinen, Oulu University Hospital, Oulu, Finland; William Arcese, Policlinico Universitario Tor Vergata, Rome, Italy; Melih Aktan, Ýstanbul Tip Fakultesi, Istanbul, Turkey; Francesco Rodeghiero, S Bortolo Hospital, Vicenza, Italy; Andrew Butler, Canterbury Health Laboratories, Christchurch, New Zealand; Michele Pizzuti, Ospedale San Carlo, Potenza, Italy; Anglea Melpignano, Perrino Hospital, Brindisi, Italy; Angelo Michele Carella, Azienda Ospedaliera Universitaria San Martino, Genova, Italy; David Valcárcel/José Sánchez de Toledo Codina, Hospital Vall d'Hebron, Barcelona, Spain; Piero Galieni, Mazzoni Hospital, Ascoli Piceno, Italy; Peter Bader, Universitätsklinikum Frankfurt, Frankfurt am Main, Germany; Dr Hahn, Buergerhospital, Stuttgart, GermanyLuigi Cavanna, Hospital Guglielmo da Saliceto, Piacenza, Italy; Gülsan Sucak, Gazi Universitesi Tip Fakültesi Hastanesi, Ankara, Turkey; Angus JM Broom, Western General Hospital, Edinburgh, UK; Pedro Gomez García, Hospital Reina Sofia, Córdoba, Spain; Emmanuelle Nicolas-Virelizier, Centre Leon Berard, Lyon, France; Vittorio Rizzoli, University of Parma, Parma, ItalyF Witz, CHU Nancy-Brabois, Nancy, France; Mike Potter, The Trustee of London Clinic, London, UK; Matthew Collin, Freeman Hospital, Newcastle Upon Tyne, UK; Mark Ringhoffer, Klinikum Karlsruhe gGmbH, Karlsruhe, Germany; Emin Kansu, Hacettepe University, Ankara, Turkey; Hans Martin, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany; José Moraleda, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain; Delphine Pranger, GHDC, Charleroi, Belgium; Richard Greil, Landeskliniken Betriebsges.mbH, Salzburg, Austria; Ali Bazarbachi, American University of Beirut Medical Center, Beirut, Lebanon; Mustafa Ozturk, Gülhane Military Medical Academy, Ankara Etlik, Turkey; Franca Fagioli, Ospedale Infantile Regina Margherita, Torino, Italy; Esa Jantunen, Kuopio University Hospital, Kuopio, Finland; Moshe Yeshurun, Beilinson Hospital, Petach-Tikva, Israel; Fevzi Altuntas, Ankara Oncology Research and Education Hospital, Ankara, Turkey; Renato Bassan, Ospedale Dell'Angelo, Venezia-Mestre, Italy; Pierre-Simon Rohrlich, CHU Nice — Hôpital de l'ARCHET I, Nice, France; Santiago Jimenez, Hospital de Gran Canaria 'Dr Negrin', Las Palmas, De Gran Canaria, Spain; Sylvie Glaisner, Centre Rene Huguenin, Saint-Cloud, France; Orazio Vinante, Civic Hospital, Noale, Italy; Johannes Clausen, Elisabethinen-Hospital, Linz, Austria; Javier López-Jiménez, Hospital Ramón y Cajal, Madrid, Spain; Koen Theunissen, Jessa Ziekenhuis, Hasselt, Belgium; Giorgina Specchia, Azienda Ospedaliero Universitaria Policlinico Bari, Bari, Italy; Vincenzo Pavone, Hospital C Panico, Tricase, Lecce, Italy; Jürgen Krauter, Städtisches Klinikum Braunschweig, Braunschweig, Germany; David Edwards, Ysbyty Gwynedd, Bangor, Wales, UK; Jose Rifón, Clínica Universitaria de Navarra, Pamplona, Spain; Hele Everaus, Tartu University Hospital, Tartu, Estonia; Gian Antonia Da Prada, Fondazione S Maugeri, Pavia, Italy; Mohammed Wattad, Kliniken Essen Süd, Essen, Germany; Giuseppe Milone, Ospedale Ferrarotto, Catania, Italy; Jan Walewski, The Maria Sklodowska-Curie Memorial Cancer Centre, Warsaw, Poland; Catherine Thieblemont, Hôpital St Louis, Paris, France; Giorgio La Nasa, Centro Trapianti di Midollo Osseo, Cagliari, ItalyMichel Duchosal, Universitaire Vaudois, Lausanne, Switzerland; Felicetto Ferrara, Cardarelli Hospital, Napoli, Italy; Alain Devidas, Centre Hospitalier Gilles de Corbeil, Corbeil-Essone, France; Alain Delmer, Hôpital Robert Debre, Reims, France; Laurent Degos, St Louis, Paris, France
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van Gelder, M., de Wreede, L., Bornhäuser, M. et al. Long-term survival of patients with CLL after allogeneic transplantation: a report from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant 52, 372–380 (2017). https://doi.org/10.1038/bmt.2016.282
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DOI: https://doi.org/10.1038/bmt.2016.282
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