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Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time

Bone Marrow Transplantation volume 36, pages 757–769 (2005)Cite this article

Summary:

We analysed a large homogeneous group of 14 403 patients transplanted for early leukaemia from an HLA-identical sibling and reported to the EBMT in four time cohorts: 1980–1989 (24%), 1990–1994 (26%), 1995–1998 (30%) and 1999–2001 (20%). We focused on death from infection. End points were survival, death from relapse and transplant-related mortality (TRM), which was subdivided into death from graft-versus-host disease (GvHD) (1315 patients; 25% of deaths), infection (597 patients; 11% of deaths) or ‘other’ causes (1875 patients; 34% of deaths). Survival increased from 52% at 5 years in the first to 62% in the third cohort (P<0.05) and TRM decreased from 36 to 26% (P<0.05) due to a reduction in death from infection (P<0.001). GvHD, ‘other’ causes and relapse did not improve. The relative proportions of bacteria (217 patients; 36%), viruses (183 patients; 31%), fungi (166 patients; 28%) or parasites (32 patients; 5%) as cause of infectious death (cumulative incidence of death at 5 years 1.8, 1.6, 1.4 and ⩾0.3%, respectively) and median time to death from infections (3 months (range 0–158 months)) did not change. Death from infections has been reduced significantly, but it still represents an ongoing risk after HSCT and draws attention to the time beyond the initial period of neutropenia.

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Acknowledgements

The cooperation of all participating teams and their staff (listed in Appendix A), the EBMT JACIE office (A Urbano-Ispizua, A Baur, P Elvy), the European EBMT Data Office in Paris (V Chesnels, NC Gorin), the EBMT Registry Subcommittee (P Ljungman, C Ruiz de Elvira), the French Registry SFGM (JP Jouet), the Dutch Registry TYPHON (A Hagenbeek, Av Biezen, N Tazelaar), the Austrian Registry (H Greinix, B Gritsch), the Czech Registry (Marie Trnkova), the Italian Registry (M Vignetti, W Arcese, R Oneto), the German Registry (H Ottinger, C Müller, B Kubanek, N Schmitz, UW Schaefer), the Swiss Registry (J Passweg, H Baldomero), the British Registry (K Towlson, N Russell), the Turkish Registry (M Arat, G Gurman), and the Spanish Transplantation Office (ONT) (M Naya) is greatly appreciated. We thank A Maerki for excellent secretarial assistance.

The work was supported in part by a grant from the European Leukaemia Net, the Swiss National Research Foundation 3200B0-106105/1, the Swiss Cancer League Oncosuisse and the Horten Foundation. EBMT is supported by grants from the corporate members: Amgen Europe, Hoffmann-La Roche Ltd, Gilead Sciences, Baxter Oncology, Pharmacia Corporation, Chugai-Aventis, Fresenius HemoCare, SangStat, Schering AG, Gambro BCT, Elan Pharmaceuticals, Miltenyl Biotec GmbH, Therakos, Wyeth-Lederlé, Astra, Cobe International, Nextar, Liposome Co., Imtix, Octapharma, Stem Cell Technologies, ICN Pharmaceuticals and Bristol-Meyers Squibb.

Author information

Authors and Affiliations

  1. Division of Hematology, University Hospitals, Basel, Switzerland

    A Gratwohl

  2. Department of Medical Statistics, EBMT Support Office, University of Leiden, The Netherlands

    R Brand

  3. Department of Hematology, Ospedale San Martino, Genova, Italy

    F Frassoni

  4. Department of Hematology, BMT Unit, Hôpital St Louis, Paris, France

    V Rocha

  5. Department of Haematology/Oncology, University of Leipzig, Germany

    D Niederwieser

  6. Division of Medicine, Hôpital du Jura, Porrentruy, Switzerland

    P Reusser

  7. Klinikum der Bayerischen Julius-Maximilian Universität, Würzburg, Germany

    H Einsele

  8. Service d'Hématologie, Hôpital Henri Mondor, Créteil, France

    C Cordonnier

Authors
  1. A Gratwohl
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  6. P Reusser
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  7. H Einsele
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Consortia

for the Acute and Chronic Leukemia Working Parties and the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation (EBMT)

Corresponding author

Correspondence to A Gratwohl.

Appendix A

Appendix A

List of participating centres for the Infection study

Algeria, Alger, R Hamladji, Centre Pierre et Marie Curie [703]

Argentina, Buenos Aires, L Feldman, Antartida Hospital Privado [742]

Australia, Melbourne, A Schwarer, Alfred Hospital [595]

Australia, Perth, R Hermann, Royal Perth Hospital [710]

Australia, Sydney, P Shaw, Children's Hospital of Westmead [711]

Austria, Graz, W Linkesch, Karl Franzens University Graz [308]

Austria, Graz, C Urban, University Children's Hospital [593]

Austria, Innsbruck, G Gastl, University Hospital Innsbruck [271]

Austria, Linz, D Lutz, Elisabethinen-Hospital [594]

Austria, Vienna, H Gadner, St Anna Hospital [528]

Austria, Vienna, H Greinix, AKH Vienna [227]

Austria, Vienna, H Ludwig, Wilhelminenspital [828]

Belarus, Minsk, O Aleinikova, Belorussian Centre for Pediatrics [591]

Belarus, Minsk, A Uss, Hospital No. 9 [801]

Belgium, Antwerp, R de Bock, AZ Middelheim [783]

Belgium, Antwerp, W Schroyens, Universiteit Antwerpen (UZA) [648]

Belgium, Brugge, D Selleslag, AZ Sint-Jan [506]

Belgium, Brussels, D Bron, Institut Jules Bordet [215]

Belgium, Brussels, A Ferrant, Cliniques Universitaires St Luc [234]

Belgium, Brussels, R Schots, University Hospital VUB [630]

Belgium, Charleroi, M Andre, CHNDRF [349]

Belgium, Gent, L Noens, University Hospital Gent [744]

Belgium, Leuven, M Boogaerts, University Hospital Gasthuisberg [209]

Belgium, Liege, Y Beguin, University of Liege [726]

Canada, Ottawa, L Huebsch, Ottawa General Hospital [351]

China, Y Wenwei, Hospital of Blood Disease [550]

Croatia, Zagreb, B Labar, University Hospital Centre-Rebro [302]

Czech Republic, Brno, J Vorlicek, University Hospital Brno [597]

Czech Republic, Hradec Králové, L Jebavy, Charles University Hospital [729]

Czech Republic, Pilsen, V Koza, Charles University Hospital [718]

Czech Republic, Prague, A Vitek, Institute of Hematology and Blood Transfusion [656]

Denmark, Copenhagen, N Jacobsen, Rigshospitalet [206]

Estonia, Tartu, H Everaus, Tartu University Clinics [746]

Finland, Helsinki, U Pihkala, Children's Hospital University of Helsinki [219]

Finland, Helsinki, T Ruutu, Helsinki University Central Hospital [515]

Finland, Turku, K Remes, Turku University Central Hospital [225]

France, Angers, M.Boasson, CHRU [650]

France, Besancon, J Cahn, Hôpital Jean Minjoz [233]

France, Caen, Leporrier, CHU de Caen [251]

France, Clamart, T de Revel, Hôpital Percy [665]

France, Clermont-Ferrand, J Bay, Centre Jean Perrin [273]

France, Clichy, J Briere, Hôpital Beaujon [662]

France, Creteil, C Cordonnier, Hôpital Henri Mondor [252]

France, Dijon, H Guy, Hôpital le Bocage [667]

France, Grenoble, J Sotto, Hôpital A.Michallon [270]

France, Lille, J Jouet, Hôpital Claude Huriez [277]

France, Lyon, M Michallet, Hôpital E.Herriot [671]

France, Lyon, N Philippe, Hôpital Debrousse [806]

France, Marseille, D Blaise, Institut Paoli Calmettes [230]

France, Marseille, C Coze, Hôpital d'Enfants de la Timone [301]

France, Montpellier, F Bernard, Hôpital Arnaud de Villeneuve [988]

France, Montpellier, J Rossi, University Hospital [926]

France, Nancy, P Lederlin, CHRU Nancy [249]

France, Nantes, J Harousseau, Hotel Dieu [253]

France, Nice, N Gratecos, Hôpital de l'Arget [523]

France, Paris, G Andreu, Pitie-Salpetriere [262]

France, Paris, A Baruchel, Hôpital St Louis [748]

France, Paris, A.Buzyn, Hôpital Necker [160]

France, Paris, F Dreyfus, Hôpital Cochin [280]

France, Paris, A Fischer, Hôpital Necker [201]

France, Paris, E Gluckman, Hôpital St Louis [207]

France, Paris, N Gorin, Hôpital St Antoine [213]

France, Paris, G Leverger, Hôpital Trousseau [675]

France, Paris, B.Rio, Hotel Dieu [222]

France, Paris, E Vilmer, Hôpital Robert Debré [631]

France, Pessac, J Reiffers, CHU-Bordeaux/Hôpital Haut-Leveque [267]

France, Poitiers, F Guilhot, Hôpital La Miletrie [264]

France, Rennes, E le Gall, CHRU de Rennes-Hôpital Sud Clinique Medicale Infantile [661]

France, Rouen, H Tilly, Centre Henri Becquerel [941]

France, Rouen, JP Vannier, Hôpital Charles Nicolle [932]

France, Saint-Etienne, D Guyotat, CHRU de Saint-Etienne Hôpital Nord [250]

France, Strasbourg, P Dufour, Hôpital de Hautepierre [672]

France, Strasbourg, P Lutz, Hôpital de Hautepierre [953]

France, Toulouse, M Attal, Hôpital de Purpan [624]

France, Toulouse, H Rubie, CHU de Purpan [952]

France, Vandoeuvre, D Sommelet, CHU de Nancy Hopitaux de Brabois-Hôpital d'Enfants [676]

France, Villejuif, J Bourhis, Institut Gustave Roussy [666]

France, Villejuif, D Machover, Hôpital Paul Brousse [567]

Germany, Augsburg, G Schlimok, II Medizinische Klinik [152]

Germany, Berlin, R Arnold, Charite [807]

Germany, Berlin, W Ebell, Charité-Virchow Klinikum [336]

Germany, Berlin, W Knauf, Klin. Benjamin Franklin, FU Berlin [590]

Germany, Berlin, W Siegert, Charite-Virchow Klinikum d.Humboldt-Un [293]

Germany, Dresden, G Ehninger, Universitätsklinikum Dresden [808]

Germany, Düsseldorf, U Göbel, Heinrich Heine Universität [651]

Germany, Düsseldorf, R Haas, Heinrich Heine Universität [390]

Germany, Erlangen, M.Gramtzki, Universität Erlangen [809]

Germany, Essen, U Schaefer, University Hospital Essen [259]

Germany, Frankfurt, D Hoelzer, Universität Frankfurt [297]

Germany, Freiburg, J Finke, University of Freiburg [810]

Germany, Hamburg, A Zander, University Hospital Eppendorf [614]

Germany, Hannover, B Hertenstein, Medical School of Hannover [295]

Germany, Heidelberg, A D Ho, University of Heidelberg [524]

Germany, Homburg, D Beelen, University of Saarland [785]

Germany, Idar-Oberstein, A Fauser, Klinik für KMT und Hämato-Onkologie [592]

Germany, Jena, H Sayer, Friedrich Schiller Universität Jena [533]

Germany, Jena, F Zintl, University of Jena [750]

Germany, Kiel, N Schmitz, Christian-Albrechts-University [256]

Germany, Leipzig, D Niederwieser, University of Leipzig [389]

Germany, Mainz, K Kolbe, Johannes-Gutenberg-University [786]

Germany, Marburg, A Neubauer, Philipps-Universität Marburg [645]

Germany, München, H Kolb, Klinikum Grosshadern [513]

Germany, Nürnberg, H Wandt, Klinikum Nürnberg [625]

Germany, Regensburg, R Andreesen, University Regensburg [787]

Germany, Rostock, M Freund, Universität Rostock [585]

Germany, Tübingen, L Kanz, Medizinische Klinik [223]

Germany, Tübingen, D Niethammer, University Hospital [535]

Germany, Ulm, L Bergmann, Universität Ulm [204]

Germany, Wiesbaden, R Schwerdtfeger, Deutsche Klinik für Diagnostik [311]

Greece, Athens, S Grafakos, ‘St Sophia’ Children's Hospital [752]

Greece, Athens, N Harhalakis, Evangelismos Hospital [622]

Greece, Athens, G Karianakis, Diagnostic and Therapeutic Centre of Athens [643]

Greece, Exokhi (Thessaloniki), A Fassas, The G.Papanicolaou Gen. Hosp. of Thessaloniki [561]

Hungary, Budapest, T Masszi, St Laszlo Hospital [739]

Hungary, Budapest, K Paloczi, National Institute of Hematology and Immunology [504]

Hungary, Miskolc, N Kalman, Postgraduate Medical School [599]

Iran, Teheran, A Ghavamzadeh, Shariati Hospital [633]

Ireland, Dublin, S McCann, St James Hospital Trinity College [257]

Ireland, Dublin, A O'Meara, Our Lady's Hospital for Sick Children [774]

Israel, Haifa, J Rowe, Rambam Medical Centre [345]

Israel, Jerusalem, S Slavin, Hadassah University Hospital [258]

Israel, Petach-Tikva, I Yaniv, Schneider Children's Med.Centre of Israel [755]

Israel, Tel-Hashomer, T Amos, Tel-Aviv University [572]

Israel, Tel-Hashomer, A Nagler, Tel-Aviv University [754]

Italy, Bergamo, T Barbui, Ospedale Bergamo [658]

Italy, Bologna, A Pession, University of Bologna [790]

Italy, Bologna, S Tura, Hospital San Orsola [240]

Italy, Brescia, T Izzi, Spedali Civili – Brescia [288]

Italy, Brescia, F Porta, Universitá degli Studi di Brescia [741]

Italy, Cagliari, G Broccia, Ospedale Oncologico [791]

Italy, Cagliari, A Cao, Ospedale Regionale Microcitemie [812]

Italy, Cagliari, L Contu, Univ. di Cagliari [811]

Italy, Catania, R Giustolisi, University of Catania [792]

Italy, Cremona, S.Morandi, Centro Trapianti Midollo Osseo, II [226]

Italy, Firenze, A Bosi, Ospedale di Careggi [304]

Italy, Genova, A Bacigalupo, Ospedale San Martino [217]

Italy, Genova, G Dini, Insitute G Gaslini [274]

Italy, Milano, C Bordignon, Isitituto Scientifico H.S. Raffaele [813]

Italy, Milano, G Lambertenghi Deliliers, Ospedale Maggiore di Milano [265]

Italy, Milano, E Morra, Ospedale di Niguarda Ca'Granda [294]

Italy, Monza, E Pogliani, Ospedale San Gerardo [544]

Italy, Monza, C Uderzo, Ospedale San Gerardo/Pediatrica [279]

Italy, Napoli, B Rotoli, University of Napoli [766]

Italy, Padova, C Messina, Clinica Oncoematologia Pediatrica e Centro Leucemie Infantili [285]

Italy, Palermo, G Mariani, Univ. di Palermo [814]

Italy, Palermo, R Scime, Ospedale V Cervello [392]

Italy, Parma, V Rizzoli, Univ. di Parma [245]

Italy, Pavia, E Alessandrino, Policlinico San Matteo IRCCS [286]

Italy, Pavia, F Locatelli, Policlinico San Matteo IRCCS/Pediatrica [557]

Italy, Perugia, M Martelli, University of Perugia [794]

Italy, Pesaro, G Lucarelli, Pesaro Hospital [529]

Italy, Pescara, P di Bartolomeo, Ospedale Civile [248]

Italy, Pisa, M Petrini, University of Pisa [795]

Italy, Reggio Calabria, P Iacopino, Azienda Ospedaliera “Bianchi-Melacrino-Morelli” [587]

Italy, Rome, S Amadori, Univ. Tor Vergata, St Eugenio Hospital [756]

Italy, Rome, W Arcese, Univ. “La Sapienza” [232]

Italy, Rome, G Leone, Universita Cattolica S Cuore [307]

Italy, Rome, I.Majolino, Ospedale San Camillo [287]

Italy, Taranto, P Mazza, Hospedale Nord [332]

Italy, Torino, F Fagioli, Ospedale Regina Margherita [305]

Italy, Torino, M Falda, Azienda Ospedaliera S Giovanni [231]

Italy, Trieste, M Andolina, Istituto Per L'Infanzia Burlo Garofolo [525]

Italy, Udine, R Fanin, Udine University Hospital [705]

Italy, Verona, F Benedetti, University of Verona [623]

Italy, Vicenza, F Rodeghiero, S Bortolo Hospital [797]

The Netherlands, Amsterdam, H van den Berg, Academic Medical Centre [247]

The Netherlands, Leiden, R Willemze, Leiden University Hospital [203]

The Netherlands, Maastricht, H Schouten, University Hospital Maastricht [565]

The Netherlands, Nijmegen, A Schattenberg, University Medical Centre, St Radboud [237]

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Gratwohl, A., Brand, R., Frassoni, F. et al. Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time. Bone Marrow Transplant 36, 757–769 (2005). https://doi.org/10.1038/sj.bmt.1705140

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