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

Michael D. Keller, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
Stefan A. Schattgen, Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.
Shanmuganathan Chandrakasan, Aflac Cancer and Blood Disorders Center, Children's Hospital of Atlanta, Atlanta, GA, USA.
E Kaitlynn Allen, Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.
Mariah A. Jensen-Wachspress, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
Christopher A. Lazarski, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
Muna Qayed, Aflac Cancer and Blood Disorders Center, Children's Hospital of Atlanta, Atlanta, GA, USA.
Haili Lang, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
Patrick J. Hanley, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
Jay Tanna, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA.
Sung-Yun Pai, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Suhag Parikh, Aflac Cancer and Blood Disorders Center, Children's Hospital of Atlanta, Atlanta, GA, USA.
Seth I. Berger, Center for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA.
Stephen Gottschalk, Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.
Michael A. Pulsipher, Division of Pediatric Hematology/Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Paul G. Thomas, Department of Immunology, St Jude Children's Research Hospital, Memphis, TN, USA.
Catherine M. Bollard, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, USA. cbollard@childrensnational.org.

Document Type

Journal Article

Publication Date

3-29-2024

Journal

Nature communications

Volume

15

Issue

1

DOI

10.1038/s41467-024-47056-3

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.

Department

Pediatrics

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