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Post-transplantation-emerging anti-HLA DQA1/DQB1 antibody possibly responsible for graft rejection after myeloablative-unrelated marrow grafting

Bone Marrow Transplantation volume 51, pages 601–603 (2016)Cite this article

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Pretransplant donor-specific anti-HLA antibodies (DSAs) have been shown to be important factors responsible for graft rejection in allogeneic stem cell transplantation (SCT).1, 2, 3 Previous studies referring to the deleterious effects of DSAs in allogeneic SCT suggested that the presence of DSAs in serum samples from pretransplant patients, not generated during the post-transplantation period, indicate a risk of graft rejection. We present the first reported case of graft rejection associated with anti-HLA DQA1/DQB1 antibody generation after SCT from an HLA-DRB1-, HLA-DQA1- and HLA-DQB1-mismatched unrelated donor.

A 4-year-old boy with mucopolysaccharidosis type II (MPS-II) was referred to the Tokai University Hospital to receive unrelated bone marrow transplantation (UBMT) to prevent neurological deterioration.4 HLA typing performed before UBMT revealed matches for HLA-A, HLA-B and HLA-C 6/6, and a mismatch for HLA-DRB1 (Table 1). HLA-DQA1 and HLA-DQB1 typing were not performed. Before referral, the patient was treated with a weekly infusion of idursulfatase, and no blood transfusion was performed. The conditioning procedure comprised busulfan (17.6 mg/kg), cyclophosphamide (200 mg/kg) and anti-thymocyte globulin (5 mg/kg; Genzyme, Cambridge, MA, USA). Prophylaxis against GvHD was performed by short-term administration of methotrexate (MTX; 15 mg/m2 per day on day 1 and 10 mg/m2 per day on post-transplantation days 3, 6 and 11) and tacrolimus (0.03 mg/kg per day continuous intravenous infusion). Granulocyte CSF at a dose of 7 μg/kg was administered from post-transplantation day 5 until a neutrophil count >1.5 × 109/L was achieved. On day 0, the patient’s peripheral blood findings showed profound myelosuppression with a white blood cell count of 0.075 × 109/L, and 3.1 × 108/kg bone marrow nucleated cells (2.6 × 106/kg bone marrow CD34-positive cells) were infused via a central venous catheter. Blood products were not transfused before graft infusion. A neutrophil count >0.5 × 109/L and a reticulocyte count >20 × 109/L were achieved at days 16 and 19, respectively. On day 25, the white blood cell count increased to 5.6 × 109/L and the reticulocyte count reached 5.4%. Donor cell engraftment was examined by the STR method, and 93.8% donor-type cells were detected by using bone marrow cells collected on day 28. The white blood cell count began to decrease from day 33, and the proportion of donor-derived CD3+ cells was reduced to 8.9% in the peripheral blood at day 39, finally resulting in complete graft rejection.

Table 1 HLA typings of the recipient, first unrelated bone marrow donor and second unrelated cord blood
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Acknowledgements

This work was supported (in part) by ‘Research on Measures for Intractable Diseases’ Project: matching fund subsidy from Ministry of Health Labour and Welfare of Japan.

Author contributions

HY and MY designed the manuscript and HY wrote the paper. SK, TS, FT and MM analyzed HLA and antibodies. All other authors contributed equally to this work. All authors approved the final version of the manuscript.

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Authors and Affiliations

  1. Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Isehara, Japan

    H Yabe, S Kato & M Yabe

  2. Department of Pediatrics, Tokai University School of Medicine, Isehara, Japan

    T Morimoto, H Takakura, R Ikegaya & H Mochizuki

  3. Department of Pediatrics, Dokkyo Medical University School of Medicine, Tochigi, Japan

    M Okuya

  4. Division of Medical Technology, Tokai University Hospital, Isehara, Japan

    T Sugimoto, F Tsuchida & M Murakami

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  1. H Yabe
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Correspondence to H Yabe.

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Yabe, H., Morimoto, T., Takakura, H. et al. Post-transplantation-emerging anti-HLA DQA1/DQB1 antibody possibly responsible for graft rejection after myeloablative-unrelated marrow grafting. Bone Marrow Transplant 51, 601–603 (2016). https://doi.org/10.1038/bmt.2015.292

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