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Late graft failure with donor-derived GPI-deficient cells in a mixed chimera following allogeneic bone marrow transplantation for severe aplastic anemia

Bone Marrow Transplantation volume 58, pages 465–468 (2023)Cite this article

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Late graft failure (LGF) associated with mixed chimerism (MC) is a serious complication that can lead to graft rejection in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT). Several risk factors for MC have been identified. These include use of reduced-intensity conditioning regimens, non-irradiation-containing regimens, and donor/recipient sex-mismatch [1,2,3]. MC is common in patients who undergo HSCT for acquired aplastic anemia (AA) because they often have these risk factors [1, 2]. When patients with MC develop progressive pancytopenia accompanied by a gradual increase in recipient cells, second HSCT usually needs to be considered to eliminate recipient-derived alloantigen-specific T cells that attack donor-derived hematopoietic stem cells (HSCs).

By contrast, donor-type LGF occurs in patients with complete donor chimerism. Although the pathogenesis of such donor-type LGF is multifactorial, donor-derived T cells specific for antigens expressed by donor HSCs are often involved in its development, and the presence of glycosylphosphatidylinositol (GPI)-anchored protein-deficient (GPI[-]) cells is thought to be evidence of immune attack on HSCs by donor T cells [4,5,6,7]. In contrast to donor-type LGFs, GPI(-) cells have never been detected in patients with MC, in whom LGF is usually caused by recipient T cells. Here, we present a case of LGF with MC that was associated with an increase in donor-derived GPI(-) cells, and eventually improved after combination therapy with cyclosporine (CsA) and the thrombopoietin-receptor agonist (TPO-RA) romiplostim (ROMI).

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Fig. 1: Clinical course after bone marrow transplantation and detection of GPI-anchored protein-deficient (GPI[−]) cells.

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Authors and Affiliations

  1. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan

    Hiroo Katsuya, Kyosuke Yamaguchi, Haruhiko Sano, Hidekazu Itamura, Sho Okamoto, Mariko Yoshimura, Hiroshi Ureshino, Toshihiko Ando & Shinya Kimura

  2. Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan

    Trung Cao Dung & Shinji Nakao

  3. Department of Infection Control and Prevention, Kanazawa University Hospital, Kanazawa, Japan

    Yoshitaka Zaimoku

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  1. Hiroo Katsuya
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Contributions

HK, KY, HS, HI, SO, MY, HU, TA, and SK treated the patient; HK and SN analyzed data, wrote, and revised the manuscript; TCD and YZ performed the experiment; and all authors reviewed the manuscript and approved it for the publication.

Corresponding authors

Correspondence to Hiroo Katsuya or Shinji Nakao.

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Competing interests

SN reports receiving honoraria from Kyowa-Kirin and Novartis. The other authors declare no conflicts of interest.

Ethical approval

The study protocol was approved by the Ethics Committee for Human Genome/Gene Analysis Research at Kanazawa University Graduate School of Medical Science and the institutional review board at Saga University Hospital. Informed consent was obtained from the patient for publication of the report.

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Katsuya, H., Yamaguchi, K., Dung, T.C. et al. Late graft failure with donor-derived GPI-deficient cells in a mixed chimera following allogeneic bone marrow transplantation for severe aplastic anemia. Bone Marrow Transplant 58, 465–468 (2023). https://doi.org/10.1038/s41409-023-01923-7

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