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Sequential allogeneic hematopoietic stem cell transplantation for active refractory/relapsed myeloid malignancies: results of a reduced-intensity conditioning preceded by clofarabine and cytosine arabinoside, a retrospective study on behalf of the SFGM-TC

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Abstract

Allogeneic stem cell transplantation (allo-SCT) represents the most beneficial treatment for patients with active relapsed/refractory (R/R) hematologic malignancies. Recently, sequential regimens combining debulking chemotherapy followed by reduced-intensity conditioning (RIC) have shown encouraging results for these patients. In this retrospective study, we report the extended results of a sequential regimen of clofarabine, cytosine arabinoside, and RIC in 131 adults with active R/R myeloid disease at transplant. Conditioning consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a rest of 3 days, by an RIC combining cyclophosphamide (60 mg/kg) for 1 day, iv busulfan (3.2 mg/kg/day) for 2 days, and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Between 2007 and 2016, 131 patients (males n = 75, median age: 52.6 years) were identified from the SFGM-TC registry. There were 111 acute myeloid leukemia (AML) patients and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was known for all but 4 patients and was primary refractory (n = 81) and 1st or 2nd relapse (n = 46). All patients received allo-SCT from a matched donor (sibling n = 64, unrelated n = 67). Engraftment was observed in 105/122 (86%) evaluable cases and 63% of the patients achieved complete remission (CR) after transplant. The 1-year overall survival, disease-free survival, relapse incidence, non-relapse mortality, and graft-versus-host disease-free/relapse-free survival were 39.2%, 28.1%, 41.0%, 30.8%, and 22.2%, respectively. This study confirms that this sequential clofarabine-based regimen provides a high CR rate in this critical population, although relapse remains a matter of concern.

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Acknowledgments

We wish to thank all investigators and data managers. We thank all staff involved in patient care for their dedication, and we especially thank the patients who took part.

Author information

Authors and Affiliations

  1. Department of Hematology, CHU Hôtel Dieu, Place A. Ricordeau, 44093, Nantes Cedex, France

    Amandine Le Bourgeois, Marie Christine Béné, Thierry Guillaume & Patrice Chevallier

  2. Department of Hematology, Hôpital Saint Antoine, Sorbonne University and INSERM UMRs 938, Paris, France

    Myriam Labopin & Mohamad Mohty

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

    Ambroise Marçais

  4. Department of Hematology, Hôpital Saint Louis & Université Paris 7, Denis Diderot, Paris, France

    Regis Peffault de Latour

  5. Department of Hematology, Centre de Recherche en Cancérologie de Marseille, Institut Paoli Calmettes, Marseille, France

    Didier Blaise

  6. Department of Hematology, CHU de Caen, Caen, France

    Sylvain Chantepie

  7. Department of Hematology, Hôpital Salpétrière, Paris, France

    Stéphanie N’Guyen

  8. Department of Hematology, Hôpital La Miletrie, Poitiers, France

    Natacha Maillard

  9. Department of Hematology, CHU de Bordeaux, Bordeaux, France

    Edouard Forcade

  10. LIRIC INSERM U995, Université Lille 2, CHU de Lille, Lille, France

    Ibrahim Yakoub-Agha

  11. Department of Hematology, CHU de Toulouse, Toulouse, France

    Anne Huynh

  12. Department of Hematology, CHU de Rennes, Rennes, France

    Tony Marchand

  13. Department of Hematology, CHU de Strasbourg, Strasbourg, France

    Karin Bilger

  14. Department of Hematology, CHU de Montpellier, Montpellier, France

    Patrice Ceballos

  15. Department of Hematology, CHU d’Amiens Sud, Amiens, France

    Amandine Charbonnier

  16. Department of Hematology, CHU de Limoges, Limoges, France

    Pascal Turlure

  17. Department of Hematology, CHU de Nancy, Nancy, France

    Marie-Thérese Rubio

Authors
  1. Amandine Le Bourgeois
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  2. Myriam Labopin
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Société Francophone de Greffe de Moelle et de Thérapie Cellulaire

Contributions

A.L.B. and P.C. designed, performed, and coordinated the research; analyzed and interpreted the data; and wrote the manuscript. M.L. performed the statistical analyses and provided the figures. F.S., R.P.d.L., D.B., S.C., S.N.G., N.M., R.T., I.Y.A., A.H., T.M., K.B., P.C., A.C., P.T., M.T.R., T.G., and M.M. contributed data and commented on the manuscript.

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Correspondence to Amandine Le Bourgeois or Patrice Chevallier.

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All patients gave informed consent for collection of their personal data in the PROMISE data base.

The study has been approved by the ethics committee of the STGM-TC.

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Le Bourgeois, A., Labopin, M., Marçais, A. et al. Sequential allogeneic hematopoietic stem cell transplantation for active refractory/relapsed myeloid malignancies: results of a reduced-intensity conditioning preceded by clofarabine and cytosine arabinoside, a retrospective study on behalf of the SFGM-TC. Ann Hematol 99, 1855–1862 (2020). https://doi.org/10.1007/s00277-020-04074-7

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