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The outcome of two or more HLA loci mismatched unrelated donor hematopoietic cell transplantation for acute leukemia: an ALWP of the EBMT study

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Abstract

A mismatched unrelated (MMUD) donor represents an alternative therapeutic option for patients who need allogeneic hematopoietic cell transplantation (allo-HCT) and do not have a human leukocyte antigen (HLA) matched donor. We studied outcomes of patients with acute leukemia transplanted from ≥2 HLA allele MMUD. The study population consisted of 465 patients. The median follow-up period was 63 and 75 months in the AML and ALL groups, respectively. The incidence of grade II–IV and grade III–IV acute (a) graft-versus-host disease (GVHD) during the first 100 days was 37% and 16%, respectively. Total and extensive chronic (c) GVHD rates at 2 years were 38% and 17%, respectively. In the entire population, the 5-year relapse incidence (RI), non-relapse mortality (NRM), leukemia-free survival (LFS), overall survival and refined GVHD-free, relapse-free survival (GRFS) was 33%, 31%, 37%, 41%, and 27%, respectively. In the multivariate analysis, HLA-DR mismatch was a poor prognostic factor, giving a significantly higher NRM [hazard ratio (HR), 1.67, p = 0.02]; poorer LFS (HR, 1.42, p = 0.03); OS (HR, 1.46, p = 0.03) and higher aGVHD grade II–IV (HR, 1.46, p = 0.05). In this study, allo-HCT from ≤6/8 HLA allele MMUD in acute leukemia patients resulted in acceptable LFS and refined GRFS. HLA-DR mismatch was a poor prognostic factor.

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Fig. 1: Transplant outcomes using a mismatched unrelated donor in patients with acute leukemia.
Fig. 2: Transplant outcomes of the patients with or without HLA-DR allele mismatch.

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Acknowledgements

We sincerely thank the centers of the EBMT and national registries for contributing patient information and data collection. Supporting information is available at the EBMT website (www.ebmt.org). Reporting institutions included in this study are available in the Online Supporting Information Appendix.

Author information

Author notes

  1. These authors contributed equally: Arnon Nagler; Bhagirathbhai Dholaria

Authors and Affiliations

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

    Arnon Nagler

  2. EBMT ALWP Office, Saint Antoine Hospital, Paris, France

    Arnon Nagler

  3. Department of Hematology-Oncology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Bhagirathbhai Dholaria & Bipin N. Savani

  4. Department of Haematology and EBMT Paris Study Office/CEREST-TC, Saint Antoine Hospital, Paris, France

    Myriam Labopin

  5. S.S.C.V.D Trapianto di Cellule Staminali, A.O.U Citta della Salute e della Scienza di Torino Presidio Molinette, Torino, Italy

    Benedetto Bruno

  6. Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, Italy

    Alessandro Rambaldi

  7. Clinica Ematologica dell’Università di Milano-Bicocca, Monza, Italy

    Pietro Pioltelli

  8. Centro Trapianti Unico Di CSE Adulti e Pediatrico A. O Brotzu, P.O. R. Binaghi, Cagliari, Italy

    Giorgio La Nasa

  9. Department of Hematology–BMT, Hopital St. Louis, Paris, France

    Gerard Socié

  10. Department of Hematology, Karolinska University Hospital, Stockholm, Sweden

    Stephan Mielke

  11. Department of Hematology, S. Bortolo Hospital, Vicenza, Italy

    Marco Ruggeri

  12. Cell Therapy and Transfusion Medicine Unit, Azienda Ospedaliera Universitaria Careggi, Firenze, Italy

    Riccardo Saccardi

  13. Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany

    Georg-Nikolaus Franke

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

    Jürgen Finke

  15. Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Roma, Italy

    Annalisa Ruggeri

  16. Sorbonne University, Paris, France

    Mohamad Mohty

  17. Service d’Hématologie Clinique et Thérapie Cellulaire, Hopital Saint-Antoine, AP-HP, Paris, France

    Mohamad Mohty

  18. INSERM, UMRs 938, Paris, France

    Mohamad Mohty

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  1. Arnon Nagler
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  2. Bhagirathbhai Dholaria
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Contributions

A.N., M.M., and M.L.-contributed to the conception and design of the study; B.D., A.N., M.L., M.M., B.N.S. contributed to the writing of the manuscript; all authors critically reviewed the manuscript and approved the final version.

Corresponding author

Correspondence to Bhagirathbhai Dholaria.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

The scientific boards of the ALWP of the EBMT approved the study. All patients gave informed consent to use their personal information for research purposes. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.

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The dataset used in this study is available at www.ebmt.org.

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Nagler, A., Dholaria, B., Labopin, M. et al. The outcome of two or more HLA loci mismatched unrelated donor hematopoietic cell transplantation for acute leukemia: an ALWP of the EBMT study. Bone Marrow Transplant 56, 20–29 (2021). https://doi.org/10.1038/s41409-020-0974-6

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