Introduction: Post-transplant BKV nephritis is a leading cause of graft loss in adults and children. No specific therapy has proven efficacy, with antiviral drugs often being ineffective and presenting frequent side effects and nephrotoxicity. The use of virus-specific T-cell therapy (VST) shows promise in treating refractory EBV, BKV, or CMV infections, including in children. We report a case of a child treated with VST, discussing cell procurement, donor selection, immunological matching, cell administration, and therapy side effects.
Methods: We present a single center experience of adjuvant treatment with VST in an 8-year-old girl with a combined Liver-Kidney transplant. She developed BKV nephropathy 2 months post-transplant, with uncontrolled viremia (up to 4E6) despite reduced immunosuppression. Leflunomide treatment was discontinued due to severe side effects (hepatotoxicity and medullary depression). High-dose IVIG was ineffective. She progressed to severe kidney failure (eGFR of 10 ml/min/1.73m²) with repeated biopsies showing severe nephritis and progressive fibrosis (up to 60%). VST cells were provided as rescue therapy by the alloCell lab of the Hannover Medical School.
A suitable donor with partial HLA-match and documented BK was identified. Optimized HLA matching included at least one match in class I and class II for recipient and graft, avoiding preexisting specific antibodies against the VST. Donor lymphocytes were collected via apheresis, activated with specific peptides, and isolated using a CliniMAC system combined with IFN-γ Cytokine Capture System. VSTs were expanded in vitro, cryopreserved, and shipped to our center in Geneva.
VSTs were bedside thawed with a water bath and rapidly injected to avoid DMSe toxicity. Five doses of 2.5E4 cells/kg were administered over 5 months, with transient side effects including fever and minor intestinal discomfort in the first 24 hours. Transient polyuria was observed, possibly linked to graft interstitial inflammation and tubular necrosis, requiring repeated i.v. fluid administration.
Results: VST therapy significantly reduced BKV viremia to 8E2 and stabilized kidney function (eGFR of 15 ml/min/1.73m²) ten months post-therapy. The most recent biopsy revealed diffuse interstitial fibrosis, affecting up to 70%. Whether VST contributed to fibrosis or if it resulted from severe inflammation due to persistent nephritis remains unclear.
Conclusion: VST aims to increase targeted immune response without further reducing immunosuppression, minimizing rejection risk. VST appears safe and effective in children, with minor and transient side effects. More studies are needed to identify patients who would benefit from VST therapy, optimal timing, and dosage of cell administration. Efficacy and long-term outcomes should be compared in RCTs to existing therapies.