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Survival advantage of treosulfan plus fludarabine (FT14) compared to busulfan plus fludarabine (FB4) in active acute myeloid leukemia post allogeneic transplantation: an analysis from the European Society for Blood and Marrow Transplantation (EBMT) Acute Leukemia Working Party (ALWP)

Bone Marrow Transplantation volume 58, pages 1084–1088 (2023)Cite this article

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Abstract

We compared FT14 (fludarabine 150–160 mg/m2, treosulfan 42 g/m2) versus FB4 (fludarabine 150–160 mg/m2, busulfan 12.8 mg/kg) in acute myeloid leukemia (AML) transplanted at primary refractory/relapsed disease. We retrospectively studied: (a) adults diagnosed with AML, (b) recipients of first allogeneic hematopoietic stem cell transplantation (HSCT) from unrelated/sibling donor (2010–2020), (c) HSCT with primary refractory/relapsed disease, (d) conditioning regimen with FT14 or FB4. We studied 346 patients, 113 transplanted with FT14, and 233 with FΒ4. FT14 patients were significantly older, more frequently had an unrelated donor and had received a lower dose of fludarabine. Cumulative incidence (CI) of acute graft-versus-host disease (GVHD) grade III-IV and extensive chronic GVHD was similar. With a median follow-up of 28.7 months, 2-year CI of relapse was 43.4% in FT14 versus 53.2% in FB4, while non-relapse mortality (NRM) was respectively 20.8% versus 22.6%. This led to 2-year leukemia-free survival (LFS) of 35.8% for FT14 versus 24.2% in FB4, and overall survival (OS) of 44.4% versus 34%. Adverse cytogenetics and conditioning regimen independently predicted CI of relapse. Furthermore, conditioning regimen was the only independent predictor of LFS, OS, and GVHD-free/relapse-free survival. Therefore, our real-world multicenter study suggests that FT14 is associated with better outcomes in primary refractory/relapsed AML.

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Fig. 1: Cumulative incidence (CI) of acute graft-versus-host disease (GVHD) grade II–IV and chronic GVHD was similar in both groups.
Fig. 2: Improved outcomes for FT14 versus FB4 in active AML.

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Data will be immediately available upon request to the corresponding author

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Acknowledgements

EG is supported by the ASH Global Research Award.

Author information

Authors and Affiliations

  1. Hematology Department-BMT Unit, G Papanikolaou Hospital, Thessaloniki, Greece

    Eleni Gavriilaki & Ioanna Sakellari

  2. Service d’ Hématologie Clinique et Thérapie Cellulaire, Hospital Saint-Antoine, Sorbonne Université, Centre de Recherche Saint-Antoine (CRSA), Paris, France

    Myriam Labopin & Mohamad Mohty

  3. University Hospital Dresden, Medizinische Klinik und Poliklinik I, TU, Dresden, Germany

    Martin Bornhäuser

  4. Centre Pierre et Marie Curie, Service Hématologie Greffe de Moëlle, Alger, Algeria

    Rose-Marie Hamladji

  5. Klinikum Oldenburg, Abt. Onkologie/Hämatologie, Oldenburg, Germany

    Jochen Casper

  6. Department. of Hematology and Oncology, University Regensburg, Regensburg, Germany

    Matthias Edinger

  7. Charles University Hospital, 4th Department of Internal Medicine – Hematology, Hradec_Kralove, Czech Republic

    Pavel Zák

  8. CHU de Lille, LIRIC, INSERM U995, Université de Lille, Lille, France

    Ibrahim Yakoub-Agha

  9. Ospedale San Raffaele s.r.l. Haematology and BMT, Milano, Italy

    Fabio Ciceri

  10. University Hospital Dept. of Bone Marrow Transplantation, Essen, Germany

    Thomas Schroeder

  11. Dept. of Hematology & BMT, Rambam Medical Center, Haifa, Israel

    Tsila Zuckerman

  12. Heinrich Heine Universitaet, Klinik für Hämat,Onkol,Klin.Immun, Duesseldorf, Germany

    Guido Kobbe

  13. Hematology and BMT Department, Beilinson Hospital, Petach_Tikva, Israel

    Moshe Yeshurun

  14. Azienda Ospedaliero Universitaria di Modena Policlinico, Ematologia, Modena, Italy

    Franco Narni

  15. Department. of Medicine -Hematology, Oncology, University of Freiburg, Freiburg, Germany

    Jürgen Finke

  16. Hospital Gregorio Marañón, Sección de Trasplante de Medula Osea, Madrid, Spain

    Jose Luiz Diez-Martin

  17. Hopital Jean Minjoz, Service d’Hématologie, Besancon, France

    Ana Berceanu

  18. Universitaetsklinikum Jena, Klinik für Innere Medizin II, (Abt. Hämatologie und Onkologie), Am Klinikum 1, Jena, Germany

    Inken Hilgendorf

  19. Klinikum Rechts der Isar, III Med Klinik der TU, Munich, Germany

    Mareike Verbeek

  20. Azienda Ospedali Riuniti di Ancona, Department of Hematology, Ancona University, Ancona, Italy

    Attilio Olivieri

  21. Department of Hematology-Oncology, Vanderbilt University, Medical Center, Nashville, TN, USA

    Bipin Savani

  22. Department of Internal Medicine, Bone Marrow Transplantation Unit, University Hospital of Patras, Patras, Greece

    Alexandros Spyridonidis

  23. Department of Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Arnon Nagler

Authors
  1. Eleni Gavriilaki
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Contributions

EG and IS designed research and wrote the original draft, provided clinical data; ML participated in research design, performed statistical analysis, and drafted the tables and figures; MB, RMH, JC, ME, PZ, IYA, FC, TS, TZ, GK, MY, FN, JF, JLDM, AB, IH, MV, AO, AN provided clinical data and edited the manuscript; BS, AS, AN and MM participated in research design and edited the manuscript. All authors approved the final manuscript.

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Correspondence to Eleni Gavriilaki.

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Gavriilaki, E., Sakellari, I., Labopin, M. et al. Survival advantage of treosulfan plus fludarabine (FT14) compared to busulfan plus fludarabine (FB4) in active acute myeloid leukemia post allogeneic transplantation: an analysis from the European Society for Blood and Marrow Transplantation (EBMT) Acute Leukemia Working Party (ALWP). Bone Marrow Transplant 58, 1084–1088 (2023). https://doi.org/10.1038/s41409-023-02028-x

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