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Recurrent secondary graft failure likely due to a DRB4 donor-specific antibody in a patient with aplastic anemia and DRB4 null allele

Bone Marrow Transplantation volume 56, pages 2603–2605 (2021)Cite this article

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Allogeneic stem cell transplant (HSCT) is a well-established treatment option in Aplastic Anemia and other bone marrow failure syndromes [1]. A different principle to malignancy applies in the conditioning and supportive care of patients with these syndromes with profound immunosuppression the cornerstone of therapy. Additionally, rejection is a potential complication; however, the role of specific donor-specific antibodies (DSA) is unclear [2]. We report a case of probable HLA-DRB4 mediated DSA rejection in an aplastic anemia patient that was overcome using a HLA-DRB4 null allele donor.

The patient was diagnosed with severe aplastic anemia in 2009. In the absence of a matched sibling bone marrow transplant donor, he commenced immunosuppressive therapy with horse anti-thymocyte globulin (ATGAM®) and ciclosporin as per standard guidelines [3]. By 2011 immunosuppressive therapy had been successfully weaned with adequate blood count. A small (3%) paroxysmal nocturnal haemoglobinuria (PNH) clone was detected by peripheral blood flow cytometry. In 2016 severe pancytopenia recurred, with a large PNH clone (type I erythrocytes 66%, type II erythrocytes 26%, granulocytes 71%, monocytes 66%). A next-generation exome panel, performed on bone marrow aspirate, did not detect commonly implicated myeloid mutations suggestive of a myelodysplastic syndrome. Treatment with Eculizumab commenced. At 3 months, the lactate dehydrogenase had reduced from 1500 to 500 U/L; however, the patient remained severely cytopenic with recurrent infections and transfusion-dependence. Therefore, the patient proceeded to peripheral blood HSCT from a matched unrelated donor. While standard guidelines for unrelated donor selection were followed [4], a strong HLA DSA to DRB4 was present in the patient, whilst the patient was demonstrated to have a HLA-DRB4 null allele. The patient typed as (using CONEXIO SBT Resolver, OneLamda Inc. LABType SSO, West Hills CA, and Immucor Mia Fora NGS Flex HLA typing Kits, Norcross, GA):

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Fig. 1: Hemoglobin, neutrophil, and platelet count after three allogeneic transplants.

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Authors and Affiliations

  1. Department of Haematology, St Vincent’s Hospital, Sydney, NSW, Australia

    Richard Blennerhassett, Annabel Horne & John Moore

  2. University of New South Wales, Medical School, Sydney, NSW, Australia

    Richard Blennerhassett & John Moore

  3. Australian Red Cross LifeBlood, NSW Transplantation and Immunogenetics Service, Sydney, NSW, Australia

    Jonathan H. Moses, Nelly Coulits, Jessica Marshall & Lyanne Weston

  4. Mid North Coast Haematology, Macquarie, NSW, Australia

    Jock Simpson

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  1. Richard Blennerhassett
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Blennerhassett, R., Moses, J.H., Coulits, N. et al. Recurrent secondary graft failure likely due to a DRB4 donor-specific antibody in a patient with aplastic anemia and DRB4 null allele. Bone Marrow Transplant 56, 2603–2605 (2021). https://doi.org/10.1038/s41409-021-01402-x

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