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Successful rescue transplantation with desensitization procedure after primary graft failure due to donor-specific antibody

Bone Marrow Transplantation volume 54, pages 1374–1376 (2019)Cite this article

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Hematopoietic stem cell transplantation from human leukocyte antigen (HLA)-haploidentical donors (haplo-SCT) is becoming an alternative option for patients without suitable donors. However, donor-specific anti-HLA antibodies (DSA), detected in ~15% among haplo-SCT recipients, are associated with higher incidence of primary graft failure (GF) [1,2,3]. Thus, desensitization procedure before stem cell infusion is recommended for DSA-positive patients [4]. Desensitization methods include antibody removal (e.g., plasma exchange), antibody neutralization (e.g., intravenous immunoglobulin (IVIg), platelet concentrate transfusion expressing DSA-targeted HLA (DSA-PC)), inhibition of additional antibody production (e.g., rituximab, bortezomib), and complement cascade inhibition (e.g., IVIg and eculizumab) [4]. Most reported cases [1, 2, 5] were concomitantly treated with these methods; thus, the efficacy of each procedure or optimal combination remains uncertain.

Recently, close association between the presence of DSAs and GF has been evident among haplo-SCT recipients: the incidence of GF is reportedly up to 30% in this setting [1,2,3,4]. Haplo-SCT recipients who experienced GF showed higher cumulative incidence of transplant-related mortality [3] and inferior overall survival than those who did not experience GF [2, 3]. Therefore, desensitizing DSAs is critical to improve transplant outcome, and as our case suggests, repeated HLA antibody test just before the conditioning could be recommended among patients with low-titer DSAs and frequent transfusion support before transplant to manage the risk of GF. Prompt re-examination of DSAs is also necessary when GF is suspected in haplo-SCT recipients, as DSAs can develop after transplantation. However, optimal management of newly identified DSAs after the first transplant remains uncertain. In this setting, treatment options might be restricted by the time frame needed for DSA reduction, accessibility, and the patients’ status. We initially employed rituximab to eliminate the remaining CD20+ B-cells, a precursor of antibody-producing plasma cells [8]. The serum half-life of rituximab is as long as 12 days [8], and its influence on the stem cell graft remains unclear; thus, we administered it on day −8, as further as possible from the second graft infusion. We added IVIg to potentiate complement cascade blockage, because its activation plays an important role in the GF development [2, 4]. Previous studies using mouse models have clarified that preformed DSA existence during stem cell infusion results in graft rejection within a few hours post-infusion [9]. From this perspective, DSA-PC is most reasonable as it efficiently eliminates DSA as fast as 3 h post-transfusion [1, 5]. Based on these findings, we conducted multiple DSA-PC transfusions even on day 0. These procedures dramatically reduced the MFI of anti-HLA B*35:01 from 14,142 to 449 (Fig. 1; day −19 and 14 of the second haplo-SCT, respectively). The MFI of anti-HLA A*11:01 only slightly decreased after the desensitization (21,564 to 18,397) compared to the targeted anti-HLA B*35, suggesting the marked effect of DSA-PCs; however, we also observed the MFI reduction of HLA class II antibodies not expressed on platelets, confirming the beneficial role of concomitant use of rituximab and IVIg (data not shown).

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Fig. 1

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  1. These authors contributed equally: Mariko Minami, Takumi Matsushima

Authors and Affiliations

  1. Department of Medicine and Biosystemic Science, Kyushu University, Graduate School of Medical Sciences, Fukuoka, Japan

    Mariko Minami, Takumi Matsushima, Yasuo Mori, Daisuke Ishihara, Fumiaki Jinnnouchi, Katsuto Takenaka, Goichi Yoshimoto, Akihiko Numata, Koji Kato, Toshihiro Miyamoto & Koichi Akashi

  2. Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka, Japan

    Tomoko Henzan & Takahiro Maeda

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  1. Mariko Minami
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Correspondence to Yasuo Mori.

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Minami, M., Matsushima, T., Mori, Y. et al. Successful rescue transplantation with desensitization procedure after primary graft failure due to donor-specific antibody. Bone Marrow Transplant 54, 1374–1376 (2019). https://doi.org/10.1038/s41409-019-0486-4

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