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HLA-DPB1 mismatch reduce relapse and improve survival in T-cell replete unrelated donor allogeneic stem cell transplantation

Bone Marrow Transplantation volume 55, pages 1658–1661 (2020)Cite this article

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Outcome of allogeneic hematopoietic stem cell transplants (HSCTs) with matched-unrelated donors (MUDs) for hematological malignancies is now comparable with human leukocyte antigen (HLA)-matched sibling donors [1]. A major contributor to this improvement is the use of high-resolution typing for HLA class I and class II gene loci [2]. Unrelated donors matched at HLA-A, -B, -C, DRB1 (8/8), and DQB1 (10/10) provide superior outcome compared with donors with one or more mismatches [2, 3]. However, HLA-DPB1 is often not included in the donor-matching algorithm [4] and 75–90% of allogeneic stem cell transplantations are performed across DPB1 matching [5, 6].

HLA-DPB1 mismatches can be further classified as permissive or non-permissive, based on T-cell epitopes shared by different HLA-DPB1 alleles [4] or the correlation between variant rs9277534, a single-nucleotide polymorphism located within the 3′-untranslated region of DPB1, and the expression level of the allele [7]. Most studies demonstrate an association between DPB1 non-permissive mismatches and risk of acute graft-vs.-host disease (GVHD). However, they report diverging incidences of relapse, transplant-related mortality (TRM), relapse-free survival (RFS), and overall survival (OS). In addition, studies differ with respect to in vivo T-cell depletion, conditioning intensity, stem cell source, and DQB1 matching [2, 6, 8,9,10]. Due to discordant data and low availability of fully matched 12/12 MUDs, the clinical significance of DPB1 matching remains unclear.

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Fig. 1: Outcome after allo-HSCT with unrelated donor dependent of HLA-DPB1 match.

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Acknowledgements

This study was supported by grants from the Swedish Research Council (2017-00355).

Funding

YF received funding from the Norwegian Cancer Society.

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Author notes

  1. These authors contributed equally: Y. Fløisand, T. Gedde-Dahl

Authors and Affiliations

  1. Department of Haematology, Oslo University Hospital, Oslo, Norway

    B. Grønvold, M. M. Ali, M. Remberger, A. E. Myhre, I. W. Abrahamsen, D. Heldal, I. Dybedal, G. E. Tjønnfjord, Y. Fløisand & T. Gedde-Dahl

  2. Department of Medical Sciences, Uppsala University and KFUE, Uppsala University Hospital, Uppsala, Sweden

    M. Remberger

  3. Gloria and Seymour Epstein Chair in Cell Therapy and Transplantation, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada

    J. Mattsson

  4. Institute of Immunology, Oslo University Hospital, Oslo, Norway

    T. Egeland & K. U. Lundin

  5. Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    T. Egeland, G. E. Tjønnfjord & T. Gedde-Dahl

  6. Centre for Cancer Cell Reprogramming, Department of Molecular Cell Biology, Oslo University Hospital, Oslo, Norway

    Y. Fløisand

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Correspondence to B. Grønvold.

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Conflict of interest

We thank The Norwegian Bone Marrow Donor Registry and Section of Transplantation Immunology, Oslo University Hospital, Oslo, for providing donor and patient data.

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Grønvold, B., Ali, M.M., Remberger, M. et al. HLA-DPB1 mismatch reduce relapse and improve survival in T-cell replete unrelated donor allogeneic stem cell transplantation. Bone Marrow Transplant 55, 1658–1661 (2020). https://doi.org/10.1038/s41409-020-0827-3

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