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

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 Tanna, Sung-Yun Pai, Suhag Parikh, Seth I. Berger, Stephen Gottschalk, Michael A. Pulsipher, Paul G. Thomas and Catherine M. Bollard ()
Additional contact information
Michael D. Keller: Children’s National Hospital
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
Jay Tanna: 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

Nature Communications, 2024, vol. 15, issue 1, 1-9

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47056-3

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