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Impact of conditioning regimen intensity on outcomes of second allogeneic hematopoietic cell transplantation for secondary acute myelogenous leukemia

Bone Marrow Transplantation volume 57, pages 1116–1123 (2022)Cite this article

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A Correction to this article was published on 07 October 2022

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Abstract

Limited data is available on factors impacting the outcomes of second hematopoietic cell transplantation (HCT2) in patients with secondary acute myeloid leukemia (sAML). This study aimed to assess HCT2 outcome for sAML comparing reduced-intensity (RIC) to myeloablative (MAC) conditioning. Two hundred and fifteen patients were included: RIC (n = 134), MAC (n = 81). The median follow-up was 41.1 (95% CI: 26.7–69.3) and 28.5 (95% CI: 23.9–75.4) months, respectively. At two years, the relapse incidence (RI) was 58.3% versus 51.1% in RIC and MAC, respectively. The 2-year leukemia free survival (LFS) was 26.6% versus 26%, and the graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) was 16.4% versus 12.1%, while OS was 31.4% and 39.7%, for RIC and MAC respectively. MVA showed a significantly lower RI [hazard ratio (HR) = 0.46 (95% CI, 0.26–0.8, p = 0.006)] and improved LFS [HR = 0.62 (95% CI, 0.39–0.98, p = 0.042)] with MAC versus RIC. The choice of conditioning regimen did not impact non-relapse mortality [HR = 1.14 (95% CI, 0.52–2.5, p = 0.74)], overall survival (OS) [HR = 0.72 (95% CI, 0.44–1.17, p = 0.18)] or GRFS [HR = 0.89 (95% CI, 0.59–1.36, p = 0.6)]. In conclusion, MAC was associated with a lower RI and superior LFS. These results support the use of MAC for eligible patients with sAML who are being considered for HCT2.

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Fig. 1: Transplant outcomes.
Fig. 2: GVHD outcomes.

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Acknowledgements

We thank all the European Society for Blood and Marrow Transplantation (EBMT) centers and national registries for contributing patients to this study (Supplementary Appendix Material). We also thank the data managers for their excellent work and the patients who contributed their data.

Author information

Authors and Affiliations

  1. Division of Hematology, Sheba Medical Center, Tel Hashomer, Israel

    Arnon Nagler

  2. ALWP of the EBMT Paris office, Paris, France

    Christophe Peczynski

  3. Vanderbilt University Medical Center, Nashville, TN, USA

    Bhagirathbhai Dholaria & Bipin N. Savani

  4. Sorbonne University, Sevice d’hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, INSERM UMRs 938, Paris, France

    Myriam Labopin & Mohamad Mohty

  5. University Medical Center Schleswig Holstein, Campus Kiel, Section for Stem Cell Transplantation and Immunotherapy, Kiel, Germany

    Thomas Valerius

  6. University of Heidelberg, Medizinische Klinik u. Poliklinik V, Heidelberg, Germany

    Peter Dreger

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

    Nicolaus Kröger

  8. University Duisburg-Essen, University Hospital Essen, Dept. of Bone Marrow Hematology and Stem Cell Transplantation, Essen, Germany

    Hans Christian Reinhardt

  9. University of Freiburg, Dept. of Medicine -Hematology, Oncology, Freiburg, Germany

    Jürgen Finke

  10. Medical Clinic and Policinic 1, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany

    Georg-Nikolaus Franke

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

    Fabio Ciceri

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

    Mareike Verbeek

  13. Medizinische Klinik m. S. Hämatologie, Onkologie und Tumorimmunologie, Charité Universitätsmedizin, Berlin, Germany

    Igor Wolfgang Blau

  14. Universitaetsklinikum Dresden, Medizinische Klinik und Poliklinik I, Dresden, Germany

    Martin Bornhäuser

  15. Hematology Stem Cell Transplant Unit, School of Medicine, University of Patras, Patras, Greece

    Alexandros Spyridonidis

  16. Department of Medicine 2, Hematology and Oncology, Goethe University Frankfurt, Frankfurt, Germany

    Gesine Bug

  17. Bone Marrow Transplantation Program, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Ali Bazarbachi

  18. Department of Hematology and Oncology, University Hospital Augsburg, Augsburg, Germany

    Christophe Schmid

  19. CHU de Lille, Univ Lille, INSERM, U1285, Lille, France

    Ibrahim Yakoub-Agha

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  1. Arnon Nagler
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Contributions

AN, MM, and ML- contributed to the conception and design of the study; ML- analyzed the data; AN, BD, BNS, ML, MM- contributed to the writing of the manuscript; All authors critically reviewed the manuscript and approved the final version.

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Correspondence to Bhagirathbhai Dholaria.

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Competing interests

HCR received consulting and lecture fees from Abbvie, AstraZeneca, Vertex and Merck. HCR received research funding from Gilead Pharmaceuticals. HCR is a co-founder of CDL Therapeutics GmbH. BD reported Institutional research funding: Takeda, Janssen, Angiocrine, Pfizer, Poseida, MEI, Sorrento. Consultancy: Jazz, Gamida Cell, MJH BioScience The remaining authors report no relevant conflict of interest concerning this work.

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The original online version of this article was revised: The caption of Fig. 1 was corrected to read “Transplant outcomes. Non-relapse mortality (a, NRM), relapse incidence (b, RI), leukemia-free survival (c, LFS), and overall survival (d, OS) of patients receiving reduced intensity versus myeloablative conditioning regimen”.

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Nagler, A., Peczynski, C., Dholaria, B. et al. Impact of conditioning regimen intensity on outcomes of second allogeneic hematopoietic cell transplantation for secondary acute myelogenous leukemia. Bone Marrow Transplant 57, 1116–1123 (2022). https://doi.org/10.1038/s41409-022-01693-8

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