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Therapy

Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid therapy followed by timed sequential chemotherapy and stem cell transplantation

Leukemia volume 14, pages 1006–1013 (2000)Cite this article

Abstract

The purpose of this study was to assess the safety and efficacy of stem cell transplantation (SCT) mainly autologous SCT as consolidation therapy in APL patients who relapsed and achieved a second complete remission (CR2). Fifty adult patients with a first relapsed APL, of whom 39 had been previously treated with ATRA, entered a multicenter trial of oral ATRA until complete remission (CR) achievement followed by timed sequential chemotherapy (EMA combining etoposide 200 mg/m2/day for 3 days, mitoxantrone 12 mg/m2/day for 3 days, and cytarabine 500 mg/m2/day for two sequences of 3 days). ema was started either after cr achievement, or on day 1 of atra because of initial white blood cell (wbc) counts >5 × 109/l, or rapidly added to ATRA in order to prevent ATRA syndrome because WBC count increased under ATRA. Forty-five patients (90%, 95% CI 78%–97%) were in CR after induction therapy. Five patients died from infection during aplasia following EMA chemotherapy. Eleven patients who achieved CR had a familial HLA-identical donor and were allografted. The median disease-free survival (DFS) of allografted patients was 8.2 months. The 34 other CR patients were scheduled for autologous peripheral blood (PB) SCT (intent-to-treat group). Actually, autologous transplantation was only carried out in 22 patients (65%) (17 PBSCT and five autologous bone marrow transplantation (BMT)). Reasons for not autografting were early relapse (three patients), severe toxicity of EMA chemotherapy (six patients), and refusal or failure of stem cell harvest (three patients). The 3-year DFS rate of patients actually autografted was 77%. Among the 17 autografted patients still in CR2, nine patients have already reached a longer CR2 than first CR (CR1). Results of detection of PML/RARα by RT-PCR after autologous transplantation show negative findings in eight of the nine patients tested. We conclude that (1) ATRA combined to EMA chemotherapy is effective in the treatment of relapsed APL; (2) allogeneic BMT may be too toxic after salvage treatment including EMA intensive chemotherapy; (3) clinical outcome of autografted patients and preliminary molecular results regarding detection of PML/RARα after autologous PBSCT are encouraging.

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Acknowledgements

This work was supported by PHRC 1995 (CHU Lille).

Author information

Authors and Affiliations

  1. Department of Hematology, Hôpital Edouard Herriot, Lyon, France

    X Thomas

  2. Department of Hematology, Hôpital St Louis, Paris, France

    H Dombret, C Chomienne & L Degos

  3. Department of Hematology, Hôpital Henri Mondor, Creteil, France

    C Cordonnier

  4. Department of Hematology, Hôpital du Haut Levêque, Pessac, France

    A Pigneux

  5. Department of Hematology, Hôpital Beaujon, Clichy, France

    C Gardin

  6. Department of Hematology, Hôpital de Brabois, Vandoeuvre, France

    A Guerci

  7. Department of Hematology, Hôpital de l'Hôtel-Dieu, Paris, France

    A Vekhoff

  8. Department of Hematology, Hôpital Jean Bernard, Poitiers, France

    A Sadoun

  9. Department of Hematology, Centre Henri Becquerel, Rouen, France

    A Stamatoullas

  10. Department of Hematology, Hôpital Lapeyronie, Montpellier, France

    N Fegueux

  11. Department of Hematology, Hôpital de Hautepierre, Strasbourg, France

    F Maloisel

  12. Department of Hematology, Hôpital Jean Minjoz, Besançon, France

    JY Cahn

  13. Department of Hematology, Hôpital Georges Clémenceau, Caen, France

    O Reman

  14. Department of Hematology, Hôpital de l'Archet, Nice, France

    N Gratecos

  15. Department of Hematology, Centre Hospitalier Universitaire, Brest, France

    C Berthou

  16. Department of Hematology, Hôpital Purpan, Toulouse, France

    F Huguet

  17. Department of Hematology, Klinika Hematologie a Transfuziologie FN, Bratislava, Slovakia, France

    P Kotoucek

  18. Department of Hematology, Hôpital de l'Hôtel-Dieu, Clermont-Ferrand, France

    P Travade

  19. Department of Hematology, Hôpital Necker-Enfants Malades, Paris, France

    A Buzyn

  20. Department of Hematology, Hôpital d'Instruction des Armées Percy, Clamart, France

    T de Revel

  21. Department of Hematology, Hôpital Robert Debré, Reims, France

    JP Vilque

  22. Department of Hematology, Institut Gustave Roussy, Villejuif, France

    P Naccache

  23. Department of Hematology, Hôpital Claude Huriez, Lille, France

    P Fenaux

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  1. X Thomas
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  2. H Dombret
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  24. L Degos
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Thomas, X., Dombret, H., Cordonnier, C. et al. Treatment of relapsing acute promyelocytic leukemia by all-trans retinoic acid therapy followed by timed sequential chemotherapy and stem cell transplantation. Leukemia 14, 1006–1013 (2000). https://doi.org/10.1038/sj.leu.2401800

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