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Therapy in APL

Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia

Leukemia volume 14, pages 1362–1370 (2000)Cite this article

Abstract

A prospective multicenter study was performed to investigate the clinical and molecular results of intensified double induction therapy including high-dose cytarabine (ara-C) in combination with ATRA in newly diagnosed acute promyelocytic leukemia (APL), followed by consolidation and 3 years maintenance therapy. Fifty-one patients, diagnosed and monitored from December 1994 to June 1999, were evaluated. The median age was 43 (16–60) years. The morphologic diagnosis was M3 in 40 (78%) and M3v in 11 (22%) patients. In 15 (30%) patients the initial white blood cell counts were ⩾5 × 109/l. The cytogenetic or molecular proof of the translocation t(15;17) was a mandatory prerequisite for eligibility. The diagnosis was confirmed by karyotyping in 46 and by RT-PCR of the PML/RARα transcript in 45 cases. The rate of complete hematological remission was 92% and the early death rate 8%. Monitoring of minimal residual disease by RT-PCR of PML/RARα (sensitivity 10−4) showed negativity in 29 of 32 (91%) evaluable cases after induction, in 23 of 25 (92%) after consolidation, and in 27 of 30 (90%) during maintenance, after a median time of 2, 4 and of 18 months after diagnosis, respectively. After a median follow-up of 27 months, the estimated actuarial 2 years overall and event-free survival were both 88% (79, 97), and the 2 years relapse-free survival 96% (90, 100). The high antileukemic efficacy of this treatment strategy is demonstrated by a rapid and extensive reduction of the malignant clone and by a low relapse rate. The results suggest that the intensity of the induction chemotherapy combined with ATRA is one of the factors which may have a critical influence on the outcome of APL. A randomized trial should assess the value of an induction therapy including ATRA and high-dose ara-C in comparison to standard-dose ara-C.

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Acknowledgements

The authors are indebted to Prof Dr Wolfgang Köpcke, University of Münster, for his biostatistical advice. We are grateful to the clinicians who entered their patients into this trial. The following institutions participated. Medizinische Klinik II, Rheinisch-Westfälische Technische Hochschule Aachen (T Ittel); Humaine Klinikum Bad Saarow (W Schulze), Krankenhaus Neukölln, Berlin (A Grüneisen); Universitätsklinikum Charité, Berlin (A Trittin); Robert-Rössle-Klinik, Humboldt-Universität, Berlin (W-D Ludwig); Knappschaftskrankenhaus Bochum (W Schmiegel); Zentralkrankenhaus Bremen (H Rasche, U Kubica); Evangelische Diakonissenanstalt Bremen (K Pflüger); Klinik I für Innere Medizin, Universität zu Köln (V Diehl, P Staib); Krankenhaus Düren (J Karow); Medizinische Klinik Heinrich-Heine-Universität Düsseldorf (C Aul, A Heyll); Medizinische Klinik II, St Johannes-Hospital Duisburg (M Westerhausen, C Schadeck-Gressel); St-Antonius-Hospital Eschweiler (R Fuchs, A Thomalla); Klinik für Knochenmarktransplantation, Universitätsklinikum Essen (U Schaefer, D Beelen); Westdeutsches Tumorzentrum, Universitätsklinikum Essen (M Nowrousian); Evangelisches Krankenhaus Essen-Werden (W Heidt, C Tirier); Zentrum Innere Medizin, Georg-August-Universität Göttingen (W Hiddemann, B Wörmann, D Haase, C Schoch); Katholisches Krankenhaus Hagen (H Eimermacher); Städtisches Krankenhaus Halle-Dölau (U Haak); Klinikum Hannover-Siloah (H Kirchner); Allgemeines Krankenhaus Altona, Hamburg (K Mainzer, D Braumann); Evangelisches Krankenhaus Hamm (L Balleisen, D Grote-Metke); Städtische Kliniken Kassel (W Hirschmann, B Eggeling); II. Medizinische Klinik, Klinikum der Christian-Albrechts-Universität Kiel (H Löffler, W Gassmann, T Haferlach); Medizinische Klinik II, Klinikum Krefeld (K Becker, M Planker); Städtisches Krankenhaus Süd, Lübeck (H Bartels); Klinikum Ludwigshafen (M Uppenkamp, M Baldus); III. Medizinische Klinik Mannheim der Universität Heidelberg (R Hehlmann, E Lengfelder); Krankenhaus Maria Hilf, Mönchen-Gladbach (HW Reis, B Trenn); Städtisches Krankenhaus München-Neuperlach (M Garbrecht, H Schäfer); Klinikum Osnabrück (J Hartlapp, T Hegge); Paracelsus-Klinik Osnabrück (O Koch); I. Medizinische Klinik, Klinikum der Universität Regensburg (R Andreesen, A Reichle); Medizinische Universitätsklinik Ulm (L Bergmann). The NB4 cell line was provided by the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmBH, Braunschweig.

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Authors and Affiliations

  1. III. Medizinische Klinik Mannheim, University of Heidelberg, Germany

    E Lengfelder, A Reichert, W Seifarth, S Saussele, A Hochhaus & R Hehlmann

  2. Department of Hematology/Oncology, University of München, Germany

    C Schoch, T Haferlach & W Hiddemann

  3. Department of Hematology/Oncology, University of Göttingen, Germany

    D Haase & B Wörmann

  4. Department of Hematology/Oncology, University of Kiel, Germany

    H Löffler & W Gassmann

  5. Department of Hematology/Oncology, University of Köln, Germany

    P Staib

  6. Department of Hematology/Oncology, University of Düsseldorf, Germany

    A Heyll & C Aul

  7. Institut für Medizinische Biologie, University of Wien, Austria

    C Fonatsch

  8. Department of Hematology/Oncology Robert-Rössle Medical Center, Humboldt University Berlin, Germany

    W-D Ludwig

  9. Klinik für Knochenmarktransplantation, University of Essen, Germany

    D Beelen

  10. Department of Biostatistics, University of Münster, Germany

    M-C Sauerland & A Heinecke

  11. Department of Hematology/Oncology, University of Münster, Germany

    T Büchner

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Lengfelder, E., Reichert, A., Schoch, C. et al. Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia. Leukemia 14, 1362–1370 (2000). https://doi.org/10.1038/sj.leu.2401843

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