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

• Published in: Nature communications Vol. 15; no. 1; pp. 2749 - 9
• Main Authors: Keller, Michael D., Schattgen, Stefan A., Chandrakasan, Shanmuganathan, Allen, E. Kaitlynn, Jensen-Wachspress, Mariah A., Lazarski, Christopher A., Qayed, Muna, Lang, Haili, Hanley, Patrick J., Tanna, Jay, Pai, Sung-Yun, Parikh, Suhag, Berger, Seth I., Gottschalk, Stephen, Pulsipher, Michael A., Thomas, Paul G., Bollard, Catherine M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.03.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/31; 45/23; 631/250/1619/554; 631/250/24/1529; 631/250/2499; 631/250/251; Adverse events; Bone marrow; Bone marrow transplantation; CD4 antigen; Chimerism; Clinical trials; Cytomegalovirus; Drug resistance; Gene expression; Graft rejection; Grafting; Humanities and Social Sciences; Immunocompromised hosts; Lymphocytes; Lymphocytes T; multidisciplinary; Peripheral blood; Rejection; Science; Science (multidisciplinary); Severe combined immunodeficiency; Side effects; T cell receptors; Transplantation; Viremia; Viruses
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-47056-3

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. Infusion of virus-specific T (VST) cells is used for treating drug-resistant viremia. Here the authors report, as part of the clinical trial, NCT03475212, a lethal case of unexpected bone marrow graft loss and chimerism reversal that is induced by the infusion of third-party VST intended to treat transplantation-related cytomegalovirus viremia.