Efficacy and Safety of Adoptive BK Polyomavirus-Reactive T-Cell Therapy for Active Infection or Disease in Transplant Recipients: A Systematic Review

Background and Objectives: BK polyomavirus (BKPyV) causes haemorrhagic cystitis (HC) after allogeneic haematopoietic cell transplantation (HCT) and nephropathy (BKPyVAN) after kidney transplantation, with no antiviral of established efficacy. We evaluated the clinical activity and treatment-emergent safety of adoptively administered BKPyV-reactive T cells. Methods: PubMed, Europe PMC and ClinicalTrials.gov were searched to 1 September 2026 with citation checking; full-length reports of therapeutic infusion were eligible and prophylaxis-only reports excluded, following PRISMA 2020 and SWiM. Results: Twenty-two reports (about eighteen analytic datasets) were included, and overlapping publications linked and not summed. Fifteen independent cohorts contributed 241 evaluable recipients, of whom 178 (73.9%) responded by their own definitions (pooled proportion 87%, 95% CI 73 to 97; I2 = 70%). Response did not follow the expected phenotype gradient (69.1% HC, 70.0% DNAemia, 75.0% BKPyVAN, overlapping intervals), and organ-level outcomes diverged: haematuria or cystitis resolved in 19 of 25 (76.0%), whereas no cohort documented consistent renal recovery once nephropathy was established. In the only placebo-controlled trial, more kidney recipients achieved a week-24 viral load decline with biweekly posoleucel than placebo, but three placebo-controlled posoleucel trials after HCT, including a phase III HC trial of 97 participants, were discontinued in December 2023 for futility without safety concerns. Acute graft-versus-host disease ranged from 0% to 25% (4.0% BKPyV-restricted, 12.2% whole-cohort denominators), rejection occurred in 4 of 69 (5.8%) exposed kidney recipients versus 0 of 19 on placebo, and one fatal cytokine-release syndrome was reported. Conclusions: BKPyV-reactive T cells show reproducible virological activity and acceptable short-term tolerability, but overlapping, mostly uncontrolled evidence does not establish comparative clinical efficacy or graft benefit. Development should target persistent DNAemia after failed reduction in immunosuppression and before irreversible fibrosis.