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Acute Leukemias

Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000

Leukemia volume 24, pages 265–284 (2010)Cite this article

Abstract

Between 1981 and 2000, 6609 children (<18 years of age) were treated in five consecutive trials of the Berlin–Frankfurt–Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL). Patients were treated in up to 82 centers in Germany, Austria and Switzerland. Probability of 10-year event-free survival (EFS) (survival) improved from 65% (77%) in study ALL-BFM 81 to 78% (85%) in ALL-BFM 95. In parallel to relapse reduction, major efforts focused on reducing acute and late toxicity through advanced risk adaptation of treatment. The major findings derived from these ALL-BFM trials were as follows: (1) preventive cranial radiotherapy could be safely reduced to 12 Gy in T-ALL and high-risk (HR) ALL patients, and eliminated in non- HR non-T-ALL patients, if it was replaced by high-dose and intrathecal (IT) MTX; (2) omission of delayed re-intensification severely impaired outcome of low-risk patients; (3) 6-month-less maintenance therapy caused an increase in systemic relapses; (4) slow response to an initial 7-day prednisone window was identified as adverse prognostic factor; (5) condensed induction therapy resulted in significant improvement of outcome; (6) the daunorubicin dose in induction could be safely reduced in low-risk patients and (7) intensification of consolidation/re-intensification treatment led to considerable improvement of outcome in HR patients.

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Acknowledgements

Support: This work was supported by grants from the Deutsche Krebshilfe, Bonn, Germany; Deutsche Leukämieforschungshilfe, Bonn, Germany and from the Madeleine-Schickedanz-Kinder-krebsstiftung, Fürth, Germany. We thank the patients and families who participated in this trial, the physicians and nurses of all hospitals for their input in performing this study and the study committee for productive discussions during the development and progress of the trial. We thank N Götz, D Janousek, U Meyer, I Krämer, K Mischke, M Gerzmehle and K Schwermer for data management, and the staff of the reference laboratories for excellent cooperation and expert diagnostics.

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Authors and Affiliations

  1. Department of Pediatrics, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany

    A Möricke, A Schrauder, M Stanulla & M Schrappe

  2. Department of Pediatric Hematology and Oncology, Medizinische Hochschule, Hannover, Germany

    M Zimmermann, K Welte, E Odenwald & H Riehm

  3. Department of Pediatric Hematology and Oncology, University Children's Hospital, Giessen, Germany

    A Reiter

  4. Department of Pediatric Hematology and Oncology, Charité, Humboldt University, Berlin, Germany

    G Henze

  5. Department of Pediatrics, St Anna Kinderspital, Vienna, Austria

    H Gadner & G Mann

  6. Department of Hematology, Oncology, and Tumor Immunology, Robert-Rössle-Clinic, HELIOS Medical Center Berlin-Buch, Berlin, Germany

    W D Ludwig

  7. Department of Pediatric Hematology and Oncology, University Children's Hospital, Münster, Germany

    J Ritter

  8. Oncogenetic Laboratory, University Children's Hospital, Giessen, Germany

    J Harbott

  9. Department of Pediatric Hematology and Oncology, University Children's Hospital, Frankfurt, Germany

    T Klingebiel

  10. Department of Pediatric Hematology and Oncology, University Children's Hospital, Jena, Germany

    F Zintl

  11. Department of Pediatric Hematology and Oncology, University Children's Hospital, Freiburg, Germany

    C Niemeyer

  12. Department of Pediatric Hematology and Oncology, University Children's Hospital, Essen, Germany

    B Kremens

  13. Department of Pediatric Hematology and Oncology, University Children's Hospital, Zürich, Switzerland

    F Niggli

  14. Department of Pediatric Hematology and Oncology, University Children's Hospital, Tübingen, Germany

    D Niethammer

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  5. A Schrauder
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  6. H Gadner
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  7. W D Ludwig
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  8. J Ritter
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  9. J Harbott
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  10. G Mann
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  11. T Klingebiel
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  14. B Kremens
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  16. D Niethammer
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  17. K Welte
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  18. M Stanulla
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  19. E Odenwald
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  21. M Schrappe
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Corresponding author

Correspondence to M Schrappe.

Additional information

Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

Supplementary information

Appendix

Appendix

Study committee (ALL-BFM 95)

Members of the study committee of the German–Austrian–Swiss ALL-BFM Study Group were as follows (all locations are in Germany, unless otherwise indicated): J Beck, Erlangen; U Bode, Bonn; J Boos, Münster; A Feldges, St Gallen, Switzerland; H Gadner, Wien, Austria; W Havers, Essen; G Henze, Berlin; B Kornhuber, Frankfurt; J Kühl, Würzburg; F Lampert, Gießen; E Maass, Stuttgart; U Mittler, Magdeburg; C Niemeyer, Freiburg; D Niethammer, Tübingen; F Niggli, Zürich, Switzerland; A Reiter, Hannover; H Riehm, Hannover; J Ritter, Münster; M Schrappe, Hannover; C Urban, Graz, Austria; H Wehinger, Kassel; K Welte, Hannover; and F Zintl, Jena.

Participating centers and clinicians

Aachen, Kinderklinik der Medizinisches Fakultät der Rheinisch-Westfälischen Technischen Hochschule (Dr R Mertens); Aarau, Kinderklinik, Hämatologie/Onkologie (Professor Dr R Imbach, Dr E Signer); Augsburg, Kinderklink I des Krankenhauszweckverbandes Augsburg, Hämatologie/Onkologie (Professor P Heidemann); Bad Mergentheim, Caritaskrankenhaus, Kinderklinik (Dr K Rager); Basel, Basler Kinderspital, Onkologie/Hämatologie Poliklinik (Professor Dr P Imbach); Bayreuth, Klinikum Bayreuth, Kinderklinik (Professor Dr GF Wündisch); Berlin, Kinderklinik der Charité, Abteilung Hämatologie/Onkologie (Professor Dr G Henze, Professor Dr G Gaedicke); Berlin, Klinikum Berlin II Buch, Kinderklinik (Dr W Dörffel); Bonn, Zentrum für Kinderheilkunde der Universität Bonn, Abteilung Pädiatrische Hämatologie/Onkologie (Professor Dr U Bode); Braunschweig, Städtisches Krankenhaus Kinderklinik (Dr W Eberl, Professor Dr G Mau); Celle, Allgemeines Krankenhaus, Kinderklinik (Professor Dr H Jacobi); Chemnitz, Klinikum Chemnitz gGmbH, Klinik für Kinder- und Jugendmedizin, Abteilung Hämatologie/Onkologie (Dr K Hofmann); Coburg, Landeskrankenhaus, Kinderklinik (Dr JD Thaben); Cottbus, Carl-Thiem-Klinikum, Kinderklinik, Abteilung Hämatologie/Onkologie (Dr D Möbius); Datteln, Vestische Kinderklinik, Universität Witten/Herdecke (Professor Dr W Andler); Delmenhorst, Städtische Kliniken, Kinderklinik (Dr C Niekrens); Dortmund, Städtische Kliniken, Kinderklinik (Dr H Breu); Dresden, Städtisches Krankenhaus, Dresden-Neustadt, Kinderklinik (Dr V Scharfe); Duisburg, Städtische Kinderklinik (Dr P Zickler); Erfurt, Helios Klinikum Erfurt GmbH, Klinik für Kinderheilkunde (Dr G Weinmann); Erlangen, Klinik für Kinder und Jugendliche der Universität Erlangen-Nürnberg (Professor Dr J-D Beck); Essen, Universitätsklinikum Essen, Kinderklinik, Hämatologie und Onkologie (Professor Dr W Havers, Dr B Kremens); Feldkirch, Landeskrankenhaus, Kinderklinik (Dr G Müller); Frankfurt/Main, Universitäts-Kinderklinik, Klinik für Kinderheilkunde III, Pädiatrische Hämatologie und Onkologie (Professor Dr B Kornhuber); Freiburg, Universitäts-Kinderklinik, Hämatologie u. Onkologie (Professor Dr C Niemeyer); Gießen, Klinikum der Justus-Liebig-Universität, Zentrum für Kinderheilkunde, Abteilung Hämatologie u. Onkologie (Professor Dr A Reiter, Professor Dr F Lampert); Göttingen, Universitäts-Kinderklinik (Professor Dr M Lakomek); Graz, Landeskrankenhaus, Universitäts-Kinderklinik, Abt. für Hämatologie/Onkologie (Professor Dr C Urban); Gummersbach, Kreiskrankenhaus Gummersbach, Kinderklinik, Hämatoonkologie (Dr V Gerein); Halle, Martin-Luther-Universität, Medizinische Fakultät, Zentrum für Kinderheilkunde, Klinik für Kinder und Jugendmedizin (Professor Dr P Exadaktylos, Professor Dr St Burdach); Hannover, Medizinische Hochschule Hannover, Kinderheilkunde IV, Pädiatrische Hämatologie und Onkologie (Professor Dr H Riehm, Professor Dr K Welte); Heidelberg, Universitäts-Kinderklinik, Pädiatrische Onkologie, Hämatologie, und Immunologie (Dr B Selle); Herdecke, Gemeinschaftskrankenhaus, Kinderabteilung (Dr Ch. Tautz); Homburg/Saar, Universitätsklinik für Kinder- und Jugendmedizin, Pädiatrische Hämatologie und Onkologie (Professor Dr N Graf); Innsbruck, Ä. ö. Landeskrankenhaus, Universitäts-Kinderklinik (Dr K Dengg); Jena, Klinikum der Friedrich-Schiller-Universität, Klinik für Kinder- und Jugendmedizin (Professor Dr F Zintl); Kaiserslautern, Westpfalz-Klinikum GmbH, Kinderklinik (Dr FJ Gutwein); Karlsruhe, Städtisches Klinikum Karlsruhe, Kinderklinik (Dr G Nessler, Dr W Dupuis); Kassel, Städtische Kinderklinik (Professor Dr H Wehinger, Dr M Rodehüser); Klagenfurt, A. ö. Krankenhaus des Landes Kärnten, Kinderinterne Abteilung (Dr W Kaulfersch); Koblenz, Städtisches Krankenhaus Kemperhof, Kinderklinik (Professor Dr M Rister); Köln, Klinik für Kinderheilkunde der Universität zu Köln (Professor Dr F Berthold); Kiel, Klinik für Allgemeine Pädiatrie, Universitäts-Kinderklinik (Professor Dr R Schneppenheim, Dr M Suttorp); Köln, Städtisches Kinderkrankenhaus (Dr W Sternschulte); Lausanne, Centre Hospitalier Universitaire Vandois, Département de pédiatrie, Unité d'onco-hematologie (Dr RM Garcia); Leipzig, Universitäts-Kinder- und Poliklinik, Abteilung Hämatologie (Dr M Domula); Leoben, Landeskrankenhaus, Kinderabteilung (Professor Dr I Mutz, Dr R Moser); Linz, Landes-Kinderkrankenhaus (Professor Dr K Schmitt, Dr G Ebetsberger); Linz, A. ö. Krankenhaus der Barmherzigen Schwestern, Kinderabteilung (Dr O Stöllinger); Locarno, Ospedale regionale, Pediatria (Dr L Nobile Buetti); Lübeck, Medizinische Universität zu Lübeck, Klinik für Pädiatrie (Professor Dr P Bucsky); Ludwigshafen, Kinderklinik St Annastift, Pädiatrische Onkologie, Hämatologie und Immunologie (Professor Dr HC Dominick); Luzern, Kantonspital Luzern, Pädiatrische Klinik, Kinderonkologie (Dr U Caflisch); Magdeburg, Otto-von-Guericke-Universität, Medizinische Fakultät, Zentrum für Kinderheilkunde (Professor Dr U Mittler); Mannheim, Klinikum der Stadt Mannheim, Kinderklinik (Dr O Sauer); Marburg, Klinikum der Philipps-Universität, Medizinisches Zentrum für Kinderheilkunde (Dr H Christiansen); Minden, Kinderklinik des Klinikum Minden (Professor Dr W Tillmann); München, Städtisches Krankenhaus München-Schwabing, Kinderklinik der Technischen Universität, Hämatologie/Onkologie (Professor Dr S Müller-Weihrich); München, Kinderpoliklinik der Ludwig-Maximilians-Universität (Professor Dr C Bender-Götze); Münster, Westfälische Wilhelms-Universität, Klinik und Poliklinik für Kinderheilkunde, Pädiatrische Hämatologie und Onkologie (Professor Dr H Jürgens, Professor Dr J Ritter); Nürnberg, Cnopf'sche Kinderklinik, Onkologie (Dr A Jobke); Nürnberg, Stadt Nürnberg-Klinikum Süd, Kinderklinik, (Dr U Schwarzer); Neunkirchen, Gemeinnützige Klinik-Gesellschaft des Landkreises Neunkirchen mbH, Kinderklinik Kohlhof (Professor O Schofer); Rostock, Universitäts-Kinderklinik K1 (Professor Dr G Eggers); Stuttgart, Olga-Hospital, Kinderklinik K1, Pädiatrisches Zentrum, Abteilung Hämatologie/Onkologie (Professor Dr J Treuner); Saarbrücken, Saarbrücker Winterbergkliniken, Gemeinnützige GmbH, Kinderklinik (Dr R Geib); Salzburg, Regional Hospital, Department of Paediatrics (Dr N Jones); Sankt Augustin, Johanniter Kinderklinik für den Rhein-Sieg-Kreis (Dr R Dickerhoff); Schwerin, Klinikum Schwerin, Kinderklinik (Dr D Neubert); Siegen, Deutsches Rotes Kreuz, Kinderklinik (Dr F-J Göbel); Steyr, Landeskrankenhaus, Kinderabteilung (Dr R Ploier); St Gallen, Ostschweizer Kinderspital, Foederatio Medicorum Helveticorum Pädiatrie, spez. Hämatologie (Dr A Feldges, Dr J Greiner); Trier, Krankenanstalt Trier, Mutterhaus der Borromäerinnen, Pädiatrische Abteilung (Professor Dr W Rauh); Tübingen, Universitäts-Kinderklinik, Abteilung Kinderheilkunde I, Hämatologie/Onkologie (Professor Dr D Niethammer, Professor Dr T Klingebiel); Ulm, Universitäts- Kinder- und Poliklinik (Professor Dr K-M Debatin, Professor E Kleihauer); Vechta, St Marienhospital, Kinderabteilung (Dr D Franke); Wien, St Anna Kinderspital (Professor Dr H Gadner, Dr Ch. Peters, Dr G Mann); Wolfsburg, Stadtkrankenhaus, Kinderklinik (Professor Dr J Otte); Würzburg, Universitäts-Kinderklinik (Dr J Kühl); Wilhelmshaven, Reinhard-Nieter-Krankenhaus, Kinderklinik (Professor Dr H-P Krohn); Zürich, Kinderspital Zürich, Universitäts-Kinderklinik (Dr F Niggli).

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Möricke, A., Zimmermann, M., Reiter, A. et al. Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000. Leukemia 24, 265–284 (2010). https://doi.org/10.1038/leu.2009.257

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