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Impact of patient: donor HLA disparity on reduced-intensity-conditioned allogeneic stem cell transplants from HLA mismatched unrelated donors for AML: from the ALWP of the EBMT

Bone Marrow Transplantation volume 56, pages 614–621 (2021)Cite this article

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Abstract

Patients with acute myeloid leukaemia (AML) who lack a matched sibling or unrelated donor commonly undergo transplantation from a donor matched at 9/10 HLA-A, -B, -C, -DRB1, -DQB1 alleles, and it is unclear if a specific locus mismatch is preferable to any other. We therefore studied 937 patients with AML in complete remission transplanted using a reduced intensity conditioning regimen from an unrelated donor mismatched at a single allele. In a multivariate analysis, patient age, adverse karyotype and patient cytomegalovirus (CMV) seropositivity were correlated with decreased leukaemia free survival (LFS) and overall survival (OS). There was no significant difference in LFS or OS between patients transplanted from donors mismatched at HLA-A, -B, -C or -DRB1 in comparison to a HLA-DQB1 mismatched transplant. In a multivariate analysis, patients transplanted with a HLA-A mismatched donor had higher rates of acute graft-versus-host disease (GVHD) and non-relapse mortality (NRM) than patients transplanted with a HLA-DQB1 mismatched donor. Patient CMV seropositivity was associated with an increase in NRM and acute GVHD and reduced LFS and OS, regardless of donor CMV status. For CMV seropositive patients lacking a fully matched donor, alternative GVHD and CMV prophylaxis strategies should be considered.

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Acknowledgements

Research support and clinical trials funding from CRUK, Bloodwise and Cure Leukaemia acknowledged. Core funding to the Birmingham ECMC Centre programme is gratefully acknowledged.

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Author notes

  1. These authors contributed equally: J Loke, M. Labopin, C Craddock

Authors and Affiliations

  1. Centre for Clinical Haematology, Queen Elizabeth Hospital, Birmingham, UK

    J. Loke & C. Craddock

  2. Paris EBMT Data Coordination Office, Hospital Saint-Antoine, APHP, Université Pierre et Marie Curie UPMC and INSERM U 938, Paris, France

    M. Labopin & M. Mohty

  3. Department of Hematology and Cell Therapy, Hospital Saint-Antoine, Paris, France

    M. Labopin & M. Mohty

  4. University of Leipzig, Leipzig, Germany

    D. Niederwieser

  5. Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands

    J. Cornelissen

  6. State Medical Pavlov University, St. Petersburg, Russia

    B. Afansayev

  7. Department of Haematology/Oncology, Charles University Hospital, Alej Svobody 80, 304 60, Pilsen, Czech Republic

    P. Jindra

  8. Department of Hematology, Acute Leukemia and Transplantation Unit, UZ Leuven, Herestraat 49, B-3000, Leuven, Belgium

    J. Maertens

  9. Transplant and Cellular Therapy Unit, Institut Paoli Calmettes, Marseille, France

    D. Blaise

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

    K. Boriskina

  11. Division of Stem Cell Transplantation and Immunotherapy, University of Kiel, Kiel, Germany

    M. Gramatzki

  12. Department of Haematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Str.1, Hannover, Germany

    A. Ganser

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

    B. Savani

  14. Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel

    A. Nagler

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  1. J. Loke
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Correspondence to C. Craddock.

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Loke, J., Labopin, M., Craddock, C. et al. Impact of patient: donor HLA disparity on reduced-intensity-conditioned allogeneic stem cell transplants from HLA mismatched unrelated donors for AML: from the ALWP of the EBMT. Bone Marrow Transplant 56, 614–621 (2021). https://doi.org/10.1038/s41409-020-01072-1

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