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Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT

Bone Marrow Transplantation volume 58, pages 506–513 (2023)Cite this article

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Abstract

In this registry-based study we retrospectively compared outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) for adult patients with acute lymphoblastic leukemia (ALL) following conditioning with total body irradiation (TBI) combined with either cyclophosphamide (Cy) or fludarabine (Flu). TBI 12 Gy + Cy was used in 2105 cases while TBI 12 Gy + Flu was administered to 150 patients in first or second complete remission. In a multivariate model adjusted for other prognostic factors, TBI/Cy conditioning was associated with a reduced risk of relapse (HR = 0.69, p = 0.049) and increased risk of grade 2–4 acute graft-versus-host disease (GVHD, HR = 1.57, p = 0.03) without significant effect on other transplantation outcomes. In a matched-pair analysis the use of TBI/Cy as compared to TBI/Flu was associated with a significantly reduced rate of relapse (18% vs. 30% at 2 years, p = 0.015) without significant effect on non-relapse mortality, GVHD and survival. We conclude that the use of myeloablative TBI/Cy as conditioning prior to allo-HCT for adult patients with ALL in complete remission is associated with lower risk of relapse rate compared to TBI/Flu and therefore should probably be considered a preferable regimen.

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Fig. 1: Allo-HCT for ALL patients according to the type of conditioning regimen. Results of a matched-pair analysis.

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Data availability

Dataset is part of the EBMT registry. It may be accessed upon request.

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Acknowledgements

We sincerely thank the centers of the EBMT for contributing patient information and data collection.

Author information

Authors and Affiliations

  1. Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland

    Sebastian Giebel

  2. Sorbonne Université, INSERM UMR-S 938, CRSA, Service d’hématologie et Thérapie Cellulaire, AP-HP, Hôpital Saint-Antoine, Paris, France

    Myriam Labopin, Eolia Brissot & Mohamad Mohty

  3. European Society for Blood and Marrow Transplantation Paris Study Office/CEREST-TC, Paris, France

    Myriam Labopin & Mohamad Mohty

  4. Hématologie APHP Hôpital Saint Louis, INSERM U976, Université de Paris, Paris, France

    Gerard Socié

  5. Oncology (Section of Adult Haematolgy/BMT), King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

    Mahmoud Aljurf

  6. Stem Cell Transplantation Unit, HUCH Comprehensive Cancer Center, Helsinki, Finland

    Urpu Salmenniemi

  7. Centre Hospitalier Lyon Sud, Pavillon Marcel Bérard -Bat 1G Service Hematologie, Lyon, France

    Hélène Labussière-Wallet

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

    Micha Srour

  9. University Hospital Eppendorf, Bone Marrow Transplantation Centre, Hamburg, Germany

    Nicolaus Kröger

  10. King Abdul - Aziz Medical City, Riyadh, Saudi Arabia

    Mohsen Al Zahrani

  11. Nouvel Hopital Civil, Strasbourg, France

    Bruno Lioure

  12. Department of Haematology and Stem Cell Transplant, Dél-pesti Centrumkórház – Országos Hematológiai és Infektológiai Intézet, Budapest, Hungary

    Péter Reményi

  13. Hematopoietic SCT Unit, Demiroglu Bilim University Istanbul Florence Nightingale Hospital, Istanbul, Turkey

    Mutlu Arat

  14. Department of Hematology, Gustave Roussy Cancer Campus BMT Service, Villejuif, France

    Jean Henri Bourhis

  15. Dept. of Haematology and BMT, Silesian Medical University, Katowice, Poland

    Grzegorz Helbig

  16. King Hussein Cancer Centre, Queen Rania Street – Aljubiha, Amman, Jordan

    Abdelghani Tbakhi

  17. CHU Bordeaux, Hôpital Haut-Leveque, Pessac, France

    Edouard Forcade

  18. CHU - Institut Universitaire du Cancer Toulouse, Oncopole, I.U.C.T-O, Toulouse, France

    Anne Huynh

  19. BMT Unit, University Hospital of Patras, Patras, Greece

    Alexandros Spirydonidis

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

    Bipin N. Savani

  21. Department of Internal Medicine, University of Zagreb School of Medicine, Zagreb, Croatia

    Zinaida Peric

  22. Hematology Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Arnon Nagler

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  1. Sebastian Giebel
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Contributions

SG designed the study, interpreted results, and wrote the manuscript; ML designed the study, performed statistical analysis, interpreted results, and reviewed the manuscript; GS, MA, US, HL-W, MS, NK, MA-Z, BL, PR, MA, JHB, GH, AT, EF, AH contributed data, interpreted results, and reviewed the manuscript; EB, AS, BNS, ZP, AN, MM designed the study, interpreted results, and reviewed the manuscript.

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Correspondence to Sebastian Giebel.

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Giebel, S., Labopin, M., Socié, G. et al. Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT. Bone Marrow Transplant 58, 506–513 (2023). https://doi.org/10.1038/s41409-023-01917-5

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