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Comparison of reduced-intensity conditioning regimens in patients with acute lymphoblastic leukemia >45 years undergoing allogeneic stem cell transplantation—a retrospective study by the Acute Leukemia Working Party of EBMT

Bone Marrow Transplantation volume 55, pages 1560–1569 (2020)Cite this article

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Abstract

The optimal reduced-intensity conditioning (RIC) for patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. We retrospectively analyzed 417 patients > 45 years with ALL in first complete remission who underwent a matched sibling or unrelated allo-HSCT and compared outcomes between fludarabine/busulfan (FLUBU, n = 127), fludarabine/melphalan (FLUMEL, n = 190), and fludarabine-TBI (FLUTBI, n = 100) conditioning. At 2 years, there were no differences between the groups in terms of cumulative incidence (CI) of relapse (40% for FLUBU vs 36% for FLUMEL vs 41% for FLUTBI, p = 0.21); transplant-related mortality (TRM) (18% for FLUBU, 22% for FLUMEL, 14% for FLUTBI, p = 0.09); overall survival (55% for FLUBU, 50% for FLUMEL, 60% for FLUTBI, p = 0.62) or leukemia-free survival (43% for FLUBU, 42% for FLUMEL, 45% for FLUTBI, p = 0.99), but GVHD-relapse-free survival was significantly lower in the FLUTBI group than FLUBU and FLUMEL group (18% vs 35% vs 28%, p = 0.02). However, this difference was lost in the multivariate analysis when adjusted for the in vivo T-cell depletion. Finally, the FLUMEL regimen was shown to be an independent risk factor for a higher TRM (HR 1.97, 95% CI 1.05–3.72, p = 0.04). We conclude that the three most popular RIC regimens yield similar transplant outcomes.

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Fig. 1: Outcomes of allo-HSCT in RIC groups.

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Authors and Affiliations

  1. University Hospital Centre Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia

    Zinaida Peric

  2. EBMT Paris study office/CEREST-TC, Saint Antoine Hospital, INSERM UMR 938, University Pierre et Marie Curie, Paris, France

    Myriam Labopin, Christophe Peczynski, Emmanuelle Polge & Arnon Nagler

  3. Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands

    Jan Cornelissen

  4. University College London Hospital, London, UK

    Ben Carpenter

  5. Royal Marsden Hospital, London, UK

    Mike Potter

  6. University Hospital Birmingham NHS Trust, Queen Elizabeth Medical Centre, Edgbaston, Birmingham, UK

    Ram Malladi

  7. Nottingham University Hospital, Nottingham, UK

    Jenny Byrne

  8. University Hospital Maastricht, Maastricht, The Netherlands

    Harry Schouten

  9. University Hospital Centre Lapeyronie, Montpellier, France

    Nathalie Fegueux

  10. Hospital St. Louis, AP-HP, University of Paris, Paris, France

    Gerard Socié

  11. Hospital Clinic, Institute of Hematology & Oncology, Barcelona, Spain

    Montserrat Rovira

  12. University Medical Centre, Utrecht, The Netherlands

    Jurgen Kuball

  13. Leeds Teaching Hospitals Trust, Leeds, UK

    Maria Gilleece

  14. Maria Sklodowska-Curie Institute—Oncology Center, Gliwice Branch, Gliwice, Poland

    Sebastian Giebel

  15. Hematology Division, Chaim Sheba Medical Centre, Tel-Hashomer, Israel

    Arnon Nagler

  16. Saint Antoine Hospital, University Pierre et Marie Curie, Paris, France

    Mohamad Mohty

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  1. Zinaida Peric
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Contributions

ZP assembled and analyzed data and wrote the first version of the manuscript. AN, SG, and MM designed the study, supervised research, analyzed data, and helped with writing the manuscript. EP, ML, and CP assembled the data, performed statistical analysis, and commented on the manuscript. All other co-authors collected data, recruited patients, and helped with writing the manuscript. All authors approved submission of the manuscript for publication.

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Correspondence to Zinaida Peric.

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Peric, Z., Labopin, M., Peczynski, C. et al. Comparison of reduced-intensity conditioning regimens in patients with acute lymphoblastic leukemia >45 years undergoing allogeneic stem cell transplantation—a retrospective study by the Acute Leukemia Working Party of EBMT. Bone Marrow Transplant 55, 1560–1569 (2020). https://doi.org/10.1038/s41409-020-0878-5

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