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Chronic Myeloid Leukemia, BCR/ABL Studies and Myelo-Proliferative Syndromes

Gender aspects in chronic myeloid leukemia: long-term results from randomized studies

Abstract

Gender-related aspects in chronic myeloid leukemia (CML) have not been studied well. We therefore analyzed 856 patients with Ph/BCR-ABL-positive CML from the German randomized CML-studies I (interferon α (IFN) vs hydroxyurea (HU) vs busulfan) and II (IFN+HU vs HU alone). The median observation time was 8.6 years. A total of 503 patients (59%) were male. Female patients were older (51 vs 46 years; P<0.0001), presented with lower hemoglobin (11.7 vs 12.5 g/dl; P<0.0001), higher platelet counts (459 vs 355 × 109/l; P<0.0001), smaller spleen size (3 vs 4 cm below costal margin; P=0.0097), a lower rate of additional cytogenetic aberrations (9 vs 15%; P=0.018) and a less favorable risk profile (P=0.036). The transplantation rate was 14% for female (n=48) and 22% for male patients (n=113). Median survival was longer in female patients (58 vs 49 months; P=0.035) mainly attributable to better survival in the low- and intermediate-risk groups and, independent from risk groups, in the HU group. These results were confirmed by matched-pair analyses based on German population data (n=496, 59 vs 45 months; P=0.0006). This is the first analysis of gender aspects in CML using randomized trials. It demonstrates the relevance of analyses of gender differences in CML and in malignant disease at large.

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Acknowledgements

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 by the Forschungsfonds der Fakultät für Klinische Medizin Mannheim der Universität Heidelberg. The assistance of Matthias Dumke, Christine Folz, Gabriele Lalla, Markus Lindauer and Margit Hummel is gratefully acknowledged. Participating institutions were as follows: Aachen: Hämatologisch-Onkologische Praxis (U Essers, L Habets); Aalen: Kreiskrankenhaus, Innere Abteilung (J-D Faulhaber); Aarau: Kantonsspital, Med. Klinik (K Giger, M Wernli); Aschaffenburg: Klinikum, Med. Klinik (W Fischbach, J Brücher); Augsburg: Zentralklinikum, II. Med. Klinik (G Schlimok); Bad Saarow: Humaine Klinikum, Klinik f. Innere Medizin (W Schultze); Basel: Kantonsspital, Hämatologie/Onkologie (A Gratwohl, A Tichelli); Bayreuth: Krankenhaus Hohe Warte, Med. Klinik (D Seybold); Berlin: Hämatologische Praxis (BR Suchy); Krankenhaus Moabit, II. Innere Abteilung (K-P Hellriegel); Krankenhaus Berlin-Neukölln, II. Innere Abteilung (AC Mayr, G Middelhoff, A Grüneisen); II. Kinderklinik Berlin-Buch (W Dörffel); Univ.-Klinikum Charlottenburg, Kinderklinik u. Poliklinik (G Henze); Hämatologisch-Onkologische Schwerpunktpraxis (I Blau); Onkol-Hämatol. Schwerpunktpraxis (I Weißenfels); Bern: Inselspital/Universitätsspital (A Tobler); Böblingen: Kreiskrankenhaus, Innere Abteilung (U Pfeilsticker, J Öller); Bonn: Universitätspoliklinik (H Vetter, YD Ko); Bremen: Zentralkrankenhaus (H Rasche, CR Meier); Bremerhaven: St Joseph-Hospital, Med. Klinik (H-H Heidtmann, A Pott); Duisburg: St-Johannes Hospital, Med. Klinik II (M Westerhausen, W Fett, C Aul); Emden: Hans-Susemihl-Krankenhaus Med. Klinik (F Lindemann); Erfurt: Hämatologische Praxis (J Weniger); Klinikum, Med. Klinik (K Wutke, D Küstner); Internistische Praxis (U Hauch); Erlangen: Med. Univ-Klinik (D Strobel, G Pongratz); Eschweiler: St-Antonius-Hospital, Hämatologie/Onkologie (R Fuchs); Frankfurt/M.: Univ.-Klinik, Zentrum der Inneren Medizin (L Bergmann, D Hoelzer, B Waßmann); Onkologische Gemeinschaftspraxis (M Fischer, Th Klippstein, F Walther); Freiburg: Med. Univ.-Klinik (L Kanz, J Finke, M Tilmann); Fürth: II. Med. Klinik (J Fink); Füssen: Kreiskrankenhaus (H Kremer); Göppingen; Klinik am Eichert, Med. Klinik II (E Kurrle, T Schmeiser); Gießen: Medizinische Klinik V, Zentrum für Innere Medizin (H Pralle); Hagen: Katholisches Krankenhaus, Hämatologie/Onkologie (H Eimermacher); Hamburg: Universitätsklinik, Hamburg-Eppendorf (DK Hossfeld, U Dührsen); Hämatologisch-Onkologische Praxis (UR Kleeberg); Allgemeines Krankenhaus Barmbek (U Müllerleile); Allgemeines Krankenhaus Altona, II. Med. Abt. (K Mainzer, Dr Meyran); Allgem. Krankenhaus St Georg (R Kuse, C zur Verth); Internistische Praxis (A Mohr); Hannover: Pathologisches Institut und Institut f. Klinische Immunologie der MHH (A Georgii, T Buhr); Institut f. Klinische Immunologie der MHH (H Deicher, P von Wussow); Heidelberg: Med. Univ.-Klinik (D Tapalaga, U Räth); Herford: Kreiskrankenhaus, Med. Klinik II (U Schmitz-Huebner); Kaiserslautern: Westpfalz-Klinikum (H Kreiter); Karlsruhe: Städt. Klinikum, II. Med. Klinik (JTh Fischer); Kempten: Klinikum Kempten-Oberallgäu, Innere Abteilung (V Hiemeyer); Kiel: Städt. Krankenhaus (H Löffler); Universitätsklinik (HD Bruhn); Köln: Universitätsklinik I. Med. Klinik (V Diehl, C Scheid); Praxisgemeinschaft (R Zankovich); Lebach: Caritas-Krankenhaus (D Hufnagl, S Kremers) Lemgo: Klinikum Lippe/Lemgo (H-P Lohrmann); Lindenfels: Luisenkrankenhaus (J Hesselmann); Ludwigshafen: St Marienkrankenhaus, Med. Klinik (HH Weiss, A Seifert); Lugano: Medicina Interna ed Ematologia FMH (E Beck); Lüneburg: Gemeinschaftspraxis (B Goldmann); Mannheim: Universitätsklinikum, III. Med. Klinik (R Hehlmann, U Berger, A Hochhaus, A Reiter, G Metzgeroth, O Maywald, W Queißer); München: Universitätsklinikum Großhadern (H-J Kolb, A Muth); Universitätsklinikum Innenstadt (B Emmerich, M Hallek); Krankenhaus München-Schwabing (C Nerl, W Kaboth); Städt. Krankenhaus München-Harlaching (R Hartenstein, N Brack); Klinikum r. d. Isar d. TU (J Rastetter, M Perker); Med. Poliklinik (N Zöllner, M Jahn-Eder); Krankenhaus München-Neuperlach, IV. Med. Abt. (M Garbrecht, HJ Schäfer); Hämatologische Praxis (A Wohlrab); Institut für Med. Informationsverarbeitung, Statistik und Biomathematik der LMU und Biometrisches Zentrum für Therapiestudien (K Überla, J Hasford, H Ansari, M Pfirrmann); Münster: Universitätsklinik, Kinderheilkunde (B Rath); Neuruppin: Ruppiner Klinikum, Med. Klinik B, (H Eggebrecht, D Nürnberg); Nürnberg: VII Medizinische Klinik (W Brockhaus), V. Medizinische Klinik (WM Gallmeier, C Falge); Oberhausen: Gemeinschaftspraxis (A Brunöhler); Oldenburg: Städt. Kliniken, Innere Medizin (F del Valle); Penzberg: Städt. Krankenhaus (K Ranft); Ravensburg: St. Elisabeth-Krankenhaus Med. Klinik (G Meuret, S Mende); Regensburg: Krankenhaus der Barmherzigen Brüder (W Wellens, J Weiß, M Schenk); Schwäbisch-Hall: Diakonie-Krankenhaus (HH Heißmeyer, T Geer); St. Gallen: Kantonsspital, Onkologische Abteilung (T Cerny, L Schmid); Traunstein: Stadtkrankenhaus, Onkologische Abteilung (G Biedermann); Ulm: Universitätsklinik, Med. Klinik III (H Heimpel, M Griesshammer); Institut f. Humangenetik (TM Fliedner, B Heinze) Waldbröl: Kreiskrankenhaus, Med. Klinik (L Labedzki); Wiesbaden: Dr-Horst-Schmidt-Kliniken GmbH (N Frickhofen, H-G Fuhr); Wilhelmshaven: St Willehad-Hospital (W Augener); Würzburg: Universitätsklinik, Med. Poliklinik (K Wilms, M Wilhelm, H Rückle-Lanz).

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Berger, U., Maywald, O., Pfirrmann, M. et al. Gender aspects in chronic myeloid leukemia: long-term results from randomized studies. Leukemia 19, 984–989 (2005). https://doi.org/10.1038/sj.leu.2403756

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