Secondary bone marrow graft loss after third-party virus-specific T cell infusion: Case report of a rare complication.
Publication Year:
2024
PubMed ID:
38553461
Funding Grants:
Public Summary:
Viral specific T-cells (VSTs) are an innovative way to treat severe viral infections in immune-compromised patients. They have generally been free from severe side effects, but we report here a unique event in a child with severe combined immune deficiency (SCID) who underwent bone marrow transplantation with T-cell depletion. One month after infusion of the VSTs, the patient rejected their marrow. The only T-cells remaining in the patient were from the VST product, suggesting that the VSTs may have caused the rejection. Caution should be used when giving this therapy very early after transplant in patients with SCID undergoing T-cell depleted bone marrow transplantation.
Scientific 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.
