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Allogeneic hematopoietic cell transplantation for older patients with AML with active disease. A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

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Abstract

Older adults with acute myeloid leukemia (AML) refractory to initial or reinduction chemotherapy have a dismal prognosis if they do not undergo hematopoietic stem-cell transplantation (HCT). However, data assessing HCT outcomes from different donors are scarce. We evaluated results from a retrospective analysis on patients aged ≥70 years, with AML not in remission who received an allogeneic HCT from HLA-matched sibling donor (MSD), HLA-10/10 matched unrelated donor (MUD), or T-cell replete haploidentical (Haplo) donor, from 2010 to 2021, reported to the ALWP-EBMT database. A total of 360 patients (median age 72 years, range 70–79) were included in the analysis. Median follow-up for the entire population was 35.5 months. Donors were MSD (n = 58), 10/10 HLA-MUD (n = 228), and Haplo (n = 74). A total of 213 (59.2%) patients were primary induction failures, while 147 (40.8%) were in first or subsequent relapse. Graft source was peripheral blood in 92% of the patients. Patients transplanted from Haplo donors more frequently received marrow grafts (p < 0.01) and presented the combination female donor to male recipient (p < 0.01). The overall 2-year rates of overall survival (OS) and leukemia-free survival (LFS) were: 62.4% (95% CI 47.2–74.3) and 47.6% (95% CI 33.1–60.8) for MSD, 43% (95% CI 35.8–49.9), and 37.5% (95% CI 30.7–44.4) for MUD, and 25.9% (95% CI 15.8–37.2), and 26.5% (95% CI 16.3–37.8) for recipients of Haplo transplants. The 2-year cumulative incidence of relapse (RI) was slightly lower for Haplo recipients at 29.6% (95% CI 19–40.9), for MUD it was 30.2% (95% CI 23.9–36.7), and for MSD 34.9% (95% CI 22–48.2); counterbalanced by a higher incidence of non-relapse mortality (NRM) of 43.9% (95% CI 31.6–55.6) for Haplo recipients, 32.2% (95% CI 26–33.1) for MUD and 17.5% (95% CI 8.4–29.3) for MSD. Graft-versus-host disease (GVHD-free, relapse-free survival (GRFS) was 35.3% (95% CI 22.3–48.5) for MSD, 29.6% (95% CI 23.2–36.2) for MUD, and 19.2% (95% CI 10.7–29.6) for Haplo patients. In the multivariate model, compared to the referent group of MSD recipients, the risk of NRM was higher among patients transplanted from Haplo donors ([hazard ratio] HR 5.1, 95% CI 2.23–11.61, p < 0.001) and MUD (HR 3.21, 95% CI 1.48–0.6.94, p = 0.003). Furthermore, both Haplo and MUD were associated with inferior OS, (HR 3.6, 95% CI 1.98–0.6.56, p < 0.001, and HR 2.3, 95% CI 1.37–0.3.88, p = 0.002, respectively), and LFS (HR 2.24, 95% CI 1.31–0.3.84, p = 0.003, and HR 1.64, 95% CI 1.04–0.2.60, p = 0.034, respectively). Patients transplanted from Haplo donors were also associated with worse GFRS (HR 1.72, 95% CI 1.07–2.77, p:0.025) compared with MSD patients. Older adult AML patients with active disease transplanted from MSD experienced prolonged OS and LFS compared to 10/10 MUD and Haplo due to lower NRM. Prospective clinical trials are warranted.

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Fig. 1: Clinical outcomes stratified by donor type.
Fig. 2: Chronic GVHD incidence and GRFS estimation by donor type.

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Data availability

Published data are available on specific request to the Acute Leukemia Working Party Chair.

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Author information

Authors and Affiliations

  1. IRCCS Azienda Ospedaliero-Universitaria di Bologna; Istituto “L. e A. Seràgnoli”, Bologna, Italy

    Enrico Maffini

  2. EBMT ALWP Statistical Unit, Paris, France

    Myriam Labopin

  3. University Medical Center Hamburg, Department for Stem Cell Transplantation, Hamburg, Germany

    Nicolaus Kröger

  4. Department of Medicine -Hematology Oncology, University of Freiburg, Freiburg, Germany

    Jürgen Finke

  5. Department of Medicine A, Hematology, Oncology, and Pneumology, University Hospital Münster, Münster, Germany

    Matthias Stelljes

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

    Thomas Schroeder

  7. Universitaetsklinikum Wuerzburg, Med. Klinik und Poliklinik II, Wuerzburg, Germany

    Herman Einsele

  8. Klinikum Grosshadern, Medizinische Klinik III, Munich, Germany

    Johanna Tischer

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

    Martin Bornhäuser

  10. Universitaet Tuebingen Medizinische Klinik, Tuebingen, Germany

    Wolfgang Bethge

  11. Deutsche Klinik fuer Diagnostik, KMT Zentrum, Wiesbaden, Germany

    Arne Brecht

  12. University Hospital Erlangen, Department of Internal Medicine 5, Erlangen, Germany

    Wolf Rösler

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

    Peter Dreger

  14. Klinikum Nuernberg, 5. Medizinische Klinik, BMT-Unit, Nuernberg, Germany

    Kerstin Schäfer-Eckart

  15. University Hospital, Hematology, Basel, Switzerland

    Jakob Passweg

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

    Igor Wolfgang Blau

  17. Sheba Medical Center, Tel-Hashomer, Tel-Aviv University, Ramat-Gan, Israel

    Arnon Nagler

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

    Fabio Ciceri

  19. Sorbonne University, Clinical Hematology and Cellular Therapy Department, Saint Antoine Hospital, INSERM UMRs 938, Paris, France

    Mohamad Mohty

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  1. Enrico Maffini
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Contributions

E.M. designed the study proposal, acquired data, interpreted the results and wrote the manuscript; M.L. performed the statistical analysis and interpreted the results. A.N. and M.M. critically appraised the paper. N.K., J.F. M.S., T.S., H.E. J.T., M.B., W.B., A.B., W.R., P.D., K.S.-E., J.P., I.W.B. and F.C. acquired data and approved the final version of the manuscript.

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Correspondence to Enrico Maffini.

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Maffini, E., Labopin, M., Kröger, N. et al. Allogeneic hematopoietic cell transplantation for older patients with AML with active disease. A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02275-6

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