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Untreated donor specific antibodies against HLA are associated with poor outcomes in peripheral blood haploidentical hematopoietic cell transplantation

Bone Marrow Transplantation volume 52, pages 898–901 (2017)Cite this article

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Donor availability has expanded considerably since work by Luznik et al.1 demonstrated that hematopoietic cell transplant (HCT) with bone marrow (BM) grafts from haploidentical (haplo) donors and post-transplantation cyclophosphamide (PTCy) was a safe and effective treatment protocol. Several studies demonstrated commensurate outcomes between haplo-HCT with PTCy and HLA-matched unrelated donor HCT.2, 3, 4 Previously, donor specific anti-HLA antibodies (DSA) were not considered significant in HCT due to the high degree of HLA matching of traditional donors. However, several recent studies have found that DSAs are highly correlated with graft failure, including one cohort of haplo-HCT with BM grafts and PTCy.5, 6, 7, 8, 9, 10, 11 Moreover, one study suggested that DSA with the ability to fix complement may play a role in the pathogenesis of graft failure in DSA-positive patients.11

We employ a modified version of this protocol utilizing G-CSF-mobilized peripheral blood stem cell (PBSC) grafts.4 The use of PBSCs is associated with significantly higher CD34+ cell dose than BM grafts.12 Data from animal models suggest that high cell doses can overwhelm DSAs and allow engraftment.13 Further, previous studies have been performed in cohorts with some patients undergoing desensitization prior to transplant. Therefore, we undertook a retrospective analysis focusing on the period before standardized treatment of DSAs was implemented at our institution.

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References

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Acknowledgements

The research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR000448, sub-award TL1TR000449, from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. We would like to acknowledge Kathryn Trinkaus, PhD, for her work on the statistical analysis for this manuscript.

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Authors and Affiliations

  1. Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    J Zou & B J Grossman

  2. Department of Medicine, Bone Marrow Transplant and Leukemia Section, Washington University, St Louis, MO, USA

    R Romee, M Slade & J Keller

  3. HLA Laboratory, Barnes-Jewish Hospital, St Louis, MO, USA

    D Phelan

  4. Norton Thoracic Institute Research Laboratory, St Joseph’s Hospital & Medical Center, Phoenix, AZ, USA

    T Mohanakumar

  5. Department of Pathology and Immunology, Washington University, St Louis, MO, USA

    B J Grossman

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  1. J Zou
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Correspondence to J Zou.

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Zou, J., Romee, R., Slade, M. et al. Untreated donor specific antibodies against HLA are associated with poor outcomes in peripheral blood haploidentical hematopoietic cell transplantation. Bone Marrow Transplant 52, 898–901 (2017). https://doi.org/10.1038/bmt.2017.7

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