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Secondary bone marrow graft loss after third-party virus-specific T cell infusion: Case report of a rare complication

Author

Listed:
  • Michael D. Keller

    (Children’s National Hospital
    Children’s National Hospital
    George Washington University)

  • Stefan A. Schattgen

    (St Jude Children’s Research Hospital)

  • Shanmuganathan Chandrakasan

    (Children’s Hospital of Atlanta)

  • E. Kaitlynn Allen

    (St Jude Children’s Research Hospital)

  • Mariah A. Jensen-Wachspress

    (Children’s National Hospital)

  • Christopher A. Lazarski

    (Children’s National Hospital)

  • Muna Qayed

    (Children’s Hospital of Atlanta)

  • Haili Lang

    (Children’s National Hospital)

  • Patrick J. Hanley

    (Children’s National Hospital
    George Washington University
    Children’s National Hospital)

  • Jay Tanna

    (Children’s National Hospital
    Children’s National Hospital)

  • Sung-Yun Pai

    (National Cancer Institute)

  • Suhag Parikh

    (Children’s Hospital of Atlanta)

  • Seth I. Berger

    (Children’s National Hospital)

  • Stephen Gottschalk

    (St Jude Children’s Research Hospital)

  • Michael A. Pulsipher

    (University of Utah)

  • Paul G. Thomas

    (St Jude Children’s Research Hospital)

  • Catherine M. Bollard

    (Children’s National Hospital
    George Washington University
    Children’s National Hospital)

Abstract

Virus-specific T cells (VST) from partially-HLA matched donors have been effective for treatment of refractory viral infections in immunocompromised patients in prior studies with a good safety profile, but rare adverse events have been described. Here we describe a unique and severe adverse event of VST therapy in an infant with severe combined immunodeficiency, who receives, as part of a clinical trial (NCT03475212), third party VSTs for treating cytomegalovirus viremia following bone marrow transplantation. At one-month post-VST infusion, rejection of graft and reversal of chimerism is observed, as is an expansion of T cells exclusively from the VST donor. Single-cell gene expression and T cell receptor profiling demonstrate a narrow repertoire of predominantly activated CD4+ T cells in the recipient at the time of rejection, with the repertoire overlapping more with that of peripheral blood from VST donor than the infused VST product. This case thus demonstrates a rare but serious side effect of VST therapy.

Suggested Citation

  • Michael D. Keller & Stefan A. Schattgen & Shanmuganathan Chandrakasan & E. Kaitlynn Allen & Mariah A. Jensen-Wachspress & Christopher A. Lazarski & Muna Qayed & Haili Lang & Patrick J. Hanley & Jay Ta, 2024. "Secondary bone marrow graft loss after third-party virus-specific T cell infusion: Case report of a rare complication," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47056-3
    DOI: 10.1038/s41467-024-47056-3
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    References listed on IDEAS

    as
    1. Mikhail Shugay & Dmitriy V Bagaev & Maria A Turchaninova & Dmitriy A Bolotin & Olga V Britanova & Ekaterina V Putintseva & Mikhail V Pogorelyy & Vadim I Nazarov & Ivan V Zvyagin & Vitalina I Kirgizova, 2015. "VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires," PLOS Computational Biology, Public Library of Science, vol. 11(11), pages 1-16, November.
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