2009/07/08 by Karen M. Frank, D. Kyle Hogarth, Jonathan Miller +5 · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · #CAR-T cell therapy research #Virus-based gene therapy research #Viral Infections and Immunology Research
paper · pdf · doi:10.1056/nejmoa0801066
openalex publication_date 2009/07/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
We present a case of disseminated histoplasmosis, complicated by retroperitoneal bleeding and leading to death, in a patient who was receiving systemic immunosuppressive therapy for rheumatoid arthritis and who was enrolled in a gene-therapy trial. This trial was designed to evaluate intraarticular delivery of a tumor necrosis factor alpha (TNF-alpha) antagonist, through an adeno-associated virus (AAV) type 2 delivery system, for inflammatory arthritis. The patient's receipt of concurrent anti-TNF-alpha therapy and other immunosuppressive therapy while she was living in an area where histoplasmosis was endemic was thought to be the most likely explanation for the infection; the evidence presented suggests that this fatal infection was unlikely to have been related to exposure to the agent administered in the gene-therapy trial. This case reinforces the importance of considering infectious complications, such as those from endemic mycoses, in patients receiving treatment with a TNF-alpha antagonist and the importance of having a well-designed monitoring plan when subjects in a research study become ill. (ClinicalTrials.gov number, NCT00126724.)