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Etoposide plus cytarabine versus cyclophosphamide or melphalan in busulfan-based preparative regimens for autologous stem cell transplantation in adults with acute myeloid leukemia in first complete remission: a study from the Acute Leukemia Working Party of the EBMT

Bone Marrow Transplantation volume 58, pages 1197–1202 (2023)Cite this article

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Abstract

We retrospectively compared the impact of the conditioning regimen in adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) that received high-dose myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) from 2010 to 2021 with either high-dose cytarabine, etoposide and busulfan (BEA), busulfan with cyclophosphamide (BUCY) or busulfan and high-dose melphalan (BUMEL) registered in the EBMT database. Overall 1560 patients underwent ASCT, of which 156, 1143 and 261 received BEA, BUCY and BUMEL, respectively. Compared to BUCY and BUMEL, BEA patients were younger (p < 0.001) and less frequently had NPM1 mutations (p = 0.03). Transplant outcomes at 5 years with BEA, BUCY and BUMEL were: cumulative incidence of relapse 41.8%, 46.6% and 51.6%; non-relapse mortality (NRM) 1.5%, 5.2% and 7.3%; probability of leukemia-free survival (LFS) 56.7%, 48.2% and 41.1%; and overall survival (OS) 71.3%, 62.3% and 56%, respectively. In multivariable analysis the BEA regimen showed significant improvement in OS compared to BUCY (hazard ratio [HR] 0.65; 95% CI, 0.42–0.83; p = 0.048) and BUMEL (HR 0.59; 95% CI, 0.37–0.94; p = 0.029). In conclusion, high-dose myeloablative combination chemotherapy with BEA offered improved outcomes compared to classical BUCY or BUMEL in patients with AML in CR1 undergoing ASCT.

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Fig. 1: Comparison of autologous stem cell transplant outcomes for patients receiving conditioning with either BEA, BUCY or BUMEL.

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Materials described in the manuscript, including all relevant raw data, will be freely available to any researcher wishing to use them for non-commercial purposes, without breaching participant confidentiality.

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Author information

Author notes

  1. These authors jointly supervised this work: Mohamad Mohty, Fabio Ciceri.

Authors and Affiliations

  1. Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain

    Jaime Sanz & Juan Montoro

  2. CIBERONC, Instituto Carlos III, Madrid, Spain

    Jaime Sanz & Juan Montoro

  3. EBMT Paris Office, Hospital Saint Antoine, Paris, France

    Myriam Labopin & Norbert Claude Gorin

  4. Department of Medical Oncology, University Hospital, Inselspital, Bern, Switzerland

    Thomas Pabst

  5. Erasmus MC Cancer Institute, Department of Hematology, University Medical Center Rotterdam, Rotterdam, The Netherlands

    Jurjen Versluis

  6. Department Internal Med.Hematology/Oncology, University Hospital Maastricht, Maastricht, The Netherlands

    Gwendolyn Van Gorkom

  7. Department of Hematology (Br 250), VU University Medical Center, Amsterdam, The Netherlands

    Ellen Meijer

  8. Clinic for Cancer Medicine, Hematology Department, Section for Stem Cell Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway

    Tobias Gedde-Dahl

  9. Tor Vergata University of Rome, Stem Cell Transplant Unit, Policlinico Universitario Tor Vergata, Rome, Italy

    William Arcese

  10. Servicio de Hematologia y Hemoterapia, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS/CISC), Sevilla, Spain

    Jose Antonio Pérez-Simón

  11. Radboud University Medical Centre, Nijmegen, The Netherlands

    Nicolaas Schaap

  12. Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium

    Johan Maertens

  13. University Hospital Center Rebro, Zagreb, Croatia

    Radovan Vrhovac

  14. Hematology Unit, Ravenna Hospital- University of Bologna, Bologna, Italy

    Francesco Lanza

  15. Hôpital Saint-Antoine, Sorbonne University, INSERM UMRs 938, Paris, France

    Norbert Claude Gorin & Mohamad Mohty

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

    Fabio Ciceri

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  1. Jaime Sanz
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  2. Myriam Labopin
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Contributions

JS, NCG, MM and FC: designed the study. ML: performed statistical analysis and helped with the interpretation of the results. JS: wrote the manuscript. TP, JV, GVG, EM, TG-D, JM, WA, JAP-S, NS, JM, RV, FL: provided patients for the study. All authors edited and approved the manuscript.

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Correspondence to Jaime Sanz.

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Sanz, J., Labopin, M., Pabst, T. et al. Etoposide plus cytarabine versus cyclophosphamide or melphalan in busulfan-based preparative regimens for autologous stem cell transplantation in adults with acute myeloid leukemia in first complete remission: a study from the Acute Leukemia Working Party of the EBMT. Bone Marrow Transplant 58, 1197–1202 (2023). https://doi.org/10.1038/s41409-023-02075-4

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