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CML, BCR/ABR Studies and Myeloproliferative Disorders

Cytogenetic response to prior treatment with interferon-α is predictive for survival after allogeneic hematopoietic stem cell transplantation in chronic myeloid leukemia

Abstract

We investigated the impact of a cytogenetic response (CyR) to IFN prior to and at the time of allogeneic hematopoietic stem cell transplantation (HSCT) on transplant-related mortality (TRM), relapse rate and survival probability after HSCT in 162 transplanted patients with chronic myeloid leukemia. One-hundred-one patients (62.3%) achieved a CyR prior to HSCT. Survival probabilities were higher in patients, who achieved any CyR prior to HSCT than in patients without CyR (63.6 vs 49.2%: P=0.019). Survival probabilities in patients, who achieved a major CyR were better than in patients with minimal and minor CyR or in patients with no CyR (69.4 vs 58.8% vs 49.2%: P=0.040). TRM and survival of chronic phase patients without CyR at the time of HSCT were similar to that of patients transplanted in advanced phase. Both groups combined had an outcome inferior to patients with at least minimal CyR (TRM, Gray test: P=0.016, survival, log-rank test: P=0.002). Univariate and multivariate analyses identified CyR prior to or at HSCT as a strong and independently favorable prognostic factor. We therefore conclude that allogeneic HSCT in CyR should be investigated prospectively as an alternative treatment option in defined patient groups.

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Acknowledgements

The assistance of Matthias Dumke, Christine Folz, Margit Hummel and Gabriele Lalla is gratefully acknowledged.

Participating institutions were as follows: Aachen: Hämatologisch-Onkologische Praxis (R Weinberg, D Tummes); Augsburg: Zentralklinikum, II. Med Klinik (G Schlimok); Bad Hersfeld: Kreiskrankenhaus (P-J Majunke); Basel: Kantonsspital, Hämatologie/Onkologie (A Gratwohl, A Tichelli); Bayreuth: Krankenhaus Hohe Warte, Med Klinik (D Seybold); Berlin: Champus Charité, Medizinische Klinik und Poliklinik II. (K Possinger); Krankenhaus Berlin-Neukölln, II. Innere Abteilung (AC Mayr, A Grüneisen); Klinik Charité Berlin, Medizinische Klinik II. mit Schwerpunkt Hämatologie, Onkologie und KMT (R Arnold); Bern: Inselspital/Universitätsspital (A Tobler); Bietigheim-Bissingen: Krankenhaus Bietigheim, Innere Medizin I (G Dietrich, S Walker); Bonn: Universitätspoliklinik (H Vetter, G Geisen); Bremen: Zentralkrankenhaus (H Rasche); Dresden: Universitätsklinikum, Medizinische Klinik und Poliklinik (G Ehninger, J Mohm); Duisburg: St-Johannes-Hospital, Med Klinik II. (C Aul); Düsseldorf: Universitätsklinikum Düsseldorf, Klinik für Hämatologie (N Gattermann); Heinrich-Heine-Univ Düsseldorf, Klinik f Hämatologie, Onkologie und klein Immunologie (R Haas); Emden: Hans-Susemihl-Krankenhaus, Med Klinik (H Becker); Erfurt: Klinikum, Med Klinik (D Küstner); Essen: Klinik und Poliklinik für KMT (DW Beelen); Frankfurt/M: Univ-Klinik, Zentrum der Inneren Medizin (L Bergmann, D Hoelzer, B Waßmann); Freiburg: Medizinische Univ-Klinik Freiburg, Innere Medizin I, Abt Hämatologie/Onkologie (J Finke); Fürth: II. Med Klinik (J Fink); Göttingen: Universität Göttingen, Abt Hämatologie/Onkologie (F Griesinger); Hagen: Katholisches Krankenhaus, Hämatologie/Onkologie (H Eimermacher); Hamburg: Allgem Krankenhaus St Georg (N Schmitz); Hämatologisch-Onkologische Praxis (UR Kleeberg); Internistische Praxis (A Mohr); Universitätsklinik, Hamburg-Eppendorf (C Bokemeyer, H Renges AR Zander); Hannover: Medizinische Hochschule Hannover, Zentrum Innere Medizin (A Ganser, D Peest); Homburg: Universitätsklinik, Innere Medizin (M Pfreundschuh); Idar-Oberstein: Klinik für Knochenmarktransplantation und Hämatologie/Onkologie (AA Fauser); Kaiserslautern: Westpfalz-Klinikum (H Link); Karlsruhe: Städt Klinikum, II. Med Klinik (JT Fischer, Y Dencausse); Kassel: Klinikum, Abt f Hämatologie/Onkologie (W-D Hirschmann); Katowice: Medical University of Silesia, Dept of Hematology (J Holowiecki, D Kata); Kempten: Klinikum Kempten-Oberallgäu, Innere Abteilung (O Prümmer); Kiel: Klinik für Allgemeine Innere Medizin (F Gieseler); Städt Krankenhaus (H Löffler); Köln: Universitätsklinik I Med Klinik (M Hallek, C Scheid); Lebach: Caritas-Krankenhaus (S Kremers); Lemgo: Klinikum Lippe/Lemgo (H-P Lohrmann); Mainz: Klinikum, Abt für Hämatologie (C Huber); Mannheim: Universitätsklinikum, III. Med Klinik (R Hehlmann, U Berger, A Hochhaus, A Reiter, T Lahaye, O Maywald); München: Klinikum r d Isar d TU (C Peschel); Krankenhaus München-Neuperlach, IV Med Abt (M Garbrecht, HJ Schäfer); Krankenhaus München-Schwabing (C Nerl); Universitätsklinikum Großhadern (W Hiddemann, H-J Kolb, A Muth); Institut für Med Informationsverarbeitung, Statistik und Biomathematik der LMU und Biometrisches Zentrum für Therapiestudien (K Überla, J Hasford, M Pfirrmann); Münster: Universitätsklinik, Kinderheilkunde (B Rath); Münster: Universitätsklinikum, Medizinische Klinik und Poliklinik (WE Berdel, M Steins); Nürnberg: Medizinische Klinik (W Brockhaus); Ravensburg: St Elisabeth-Krankenhaus, Med Klinik (S Mende, A Egger, G Wiedemann); Regensburg: Krankenhaus der Barmherzigen Brüder (ED Kreuser, M Schenk); Universitätsklinikum Regensburg, Innere Medizin 1 (S Krause); St Gallen: Kantonsspital, Onkologische Abteilung (HJ Senn, T Cerny, U Hess); Stuttgart: Bürgerhospital Stuttgart, Medizinische Klinik 1 (W Grimminger, H Benöhr); Diakonie-Klinikum, Medizinische Klinik II. (R Mück, E Heidemann); Tübingen: Universitätsklinikum, Innere Medizin II. (L Kanz); Ulm: Universitätskinderklinik (A Schulz, E Kohne); Universitätsklinik, Med Klinik III. (H Döhner, M Griesshammer); Waldbröl: Kreiskrankenhaus, Med Klinik (L Labedzki); Wien: Universitätsklinik für Innere Medizin I (K Lechner); Wiesbaden: Dr-Horst-Schmidt-Kliniken GmbH (N Frickhofen, H-G Fuhr); Deutsche Klinik für Diagnostik, Zentrum für Knochenmarktransplantation (R Schwerdtfeger); Würzburg: Universitätsklinik, Med Poliklinik (K Wilms, M Wilhelm, H Rückle-Lanz, ME Goebeler); Zürich: Universitätsspital Zürich, Hämatologie (J Gmür).

The study was supported by a grant from the German Ministry of Education and Research (BMBF), Competence network ‘Acute and chronic leukemias’-01 GI9980/6, by a grant of Hoffmann-La Roche to the Süddeutsche Hämoblastosegruppe (SHG), by the Gesellschaft für Informationsverarbeitung und Statistik in der Medizin (GIS), München, and the Swiss National Research Foundation.

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Maywald, O., Pfirrmann, M., Berger, U. et al. Cytogenetic response to prior treatment with interferon-α is predictive for survival after allogeneic hematopoietic stem cell transplantation in chronic myeloid leukemia. Leukemia 20, 477–484 (2006). https://doi.org/10.1038/sj.leu.2404100

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