Outcome Analysis Post Virus-Specific T Cell Therapy for the Treatment of Adenoviremia in Immunocompromised Pediatric Patients

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Introduction Adenovirus infection poses a major risk to immunocompromised patients, including those with inborn errors of immunity (IEI) and those undergoing hematopoietic cell transplant (HCT). Adoptive immunotherapy using virus-specific T cells (VSTs) has emerged as a promising therapeutic approach. Detailed outcomes of VST therapy specifically for adenovirus in pediatric patients remains poorly understood. Further, treatment of adenoviremia is often a smaller component of larger studies addressing multiple viral infections. Over 500 patients globally have received adenovirus-specific VSTs post-HCT in the academic setting, though comprehensive studies focusing exclusively on pediatric populations are limited. Objectives To evaluate the efficacy and safety of adenovirus-specific VSTs in pediatric patients with adenoviremia following HCT. Methods We analyzed patients who received VSTs for adenoviral infection post-HCT through our Program between 2013-2024. A complete response (CR) was defined as resolution of viremia and clinical disease, while a partial response (PR) was defined as a sustained reduction in viral load of > 1 log. Statistical analysis was performed by two-tailed T tests. Results Forty-four patients received 1–3 VST infusions for adenoviral infection following HCT. Underlying diagnoses were IEI (n=22), hematologic malignancy (n=20), or other non-malignant diseases (n=2). VSTs were derived from HCT donors (n=9) or third-party donors (n=35), and given at a median of 88 days post HCT. Most patients (n=35) also received antiviral therapy (cidofovir or brincidofovir). Overall response rate was 73% (28 CR, 4 PR) (95% CI, 64% to 82%), with a median response time of 16 days post-infusion. Adverse events included grade II to IV GVHD (n=5, with two de novo), cytokine release syndrome (n=2), and neurologic disease (n=2). There was no association between overall HLA match (p=0.32), or day of infusion post HCT (p=0.90) and likelihood of antiviral response. Conclusions VST therapy is generally well-tolerated and effective against adenovirus in pediatric patients post-HCT. This study represents one of the largest pediatric series focused solely on adenovirus-specific VST therapy. Future VST trials may further define associated risks, and gene-editing approaches could enhance treatment efficacy, especially in the context of immunosuppression.

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