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The role of anti-thymocyte globulin in allogeneic stem cell transplantation (HSCT) from HLA-matched unrelated donors (MUD) for secondary AML in remission: a study from the ALWP /EBMT

Bone Marrow Transplantation volume 58, pages 1339–1347 (2023)Cite this article

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Abstract

We compared outcomes, of 1609 patients with secondary acute myeloid leukemia (sAML) undergoing allogeneic transplantation (HSCT) in first complete remission (CR1) from matched unrelated donors (MUD) from 2010 to 2021, receiving or not receiving anti-thymocyte globulin (ATG) (ATG-1308, no ATG-301). Median age was 60.9 (range, 18.5–77.8) and 61.1 (range, 21.8–75.7) years, (p = 0.3). Graft versus host disease (GVHD) prophylaxis was cyclosporin-A with methotrexate (41%) or mycophenolate mofetil (38.2%), without significant differences between groups. Day 28, engraftment (ANC > 0.5 × 109/L) was 92.3% vs 95.3% (p = 0.17), respectively. On multivariate analysis, ATG was associated with lower incidence of grade II-IV and grade III-IV acute GVHD (p = 0.002 and p = 0.015), total and extensive chronic GVHD (p = 0.008 and p < 0.0001), and relapse incidence (RI) (p = 0.039), while non-relapse mortality (NRM) did not differ (p = 0.51). Overall survival (OS), and GVHD-free, relapse-free survival (GRFS) were significantly higher in the ATG vs no ATG group, HR = 0.76 (95% CI 0.61–0.95, p = 0.014) and HR = 0.68 (95% CI 0.57–0.8, p < 0.0001), with a tendency for better leukemia-free survival (LFS), HR = 0.82 (95% CI 0.67–1, p = 0.051). The main causes of death were the original disease, infection, and GVHD. In conclusion, ATG reduces GVHD and improves LFS, OS, and GRFS in sAML patients without increasing the RI, despite sAML being a high-risk disease.

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Fig. 1: Outcome of allogeneic stem cell transplantation (HSCT) from unrelated donors with or without anti-thymocyte globulin (ATG) in patients with secondary acute myeloid leukemia (sAML).

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AN, ML, and MM had full access to all study data (available upon data-specific request).

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Acknowledgements

We thank all the EBMT centers and national registries for contributing patients to this study (Supplementary Appendix material). We also thank the data managers for their excellent work.

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Authors and Affiliations

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

    Arnon Nagler

  2. EBMT Paris study office; Department of Haematology, Saint Antoine Hospital, Sorbonne University, INSERM UMR 938, Paris, France

    Myriam Labopin & Mohamad Mohty

  3. Sorbonne University, Department of Haematology, Saint Antoine Hospital; INSERM UMR 938, Paris, France

    Myriam Labopin & Mohamad Mohty

  4. Department of Stem Cell Transplantation, University Medical Center, Hamburg, Germany

    Nicolaus Kröger

  5. University Hospital, Department of Bone Marrow Transplantation, Essen, Germany

    Thomas Schroeder

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

    Tobias Gedde-Dahl

  7. Hannover Medical School, Department of Haematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover, Germany

    Matthias Eder

  8. Medical Clinic and Policinic 1, Hematology and Cellular Therapy University hospital Leipzig, Leipzig, Germany

    Georg-Nikolaus Franke

  9. Charité, University medicine Berlin, Department of Hematology, BMT Unit, Berlin, Germany

    Igor Wolfgang Blau

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

    Urpu Salmenniemi

  11. Hopital St. Louis, Department of Hematology—BMT, Paris, France

    Gerard Socie

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

    Johannes Schetelig

  13. University of Muenster Department of Hematol. /Oncol., Muenster, Germany

    Matthias Stelljes

  14. Hematology & Bone Marrow Transplant, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Fabio Ciceri

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  1. Arnon Nagler
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Contributions

AN wrote the manuscript, designed the study, and interpreted the data. ML and MM designed the study, performed the statistical analyses, interpreted the data, and edited the manuscript. NK, TS, TGD, ME, UP, IWB, US, RPDL, JS, MS, BS, and FC reviewed the manuscript and provided clinical data. All authors approved the final version of the manuscript.

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Correspondence to Arnon Nagler.

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The authors declare that they have no relevant conflict of interest and no competing financial interests. NK received a research grant and honorarium from Neovii.

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Nagler, A., Labopin, M., Kröger, N. et al. The role of anti-thymocyte globulin in allogeneic stem cell transplantation (HSCT) from HLA-matched unrelated donors (MUD) for secondary AML in remission: a study from the ALWP /EBMT. Bone Marrow Transplant 58, 1339–1347 (2023). https://doi.org/10.1038/s41409-023-02095-0

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