Hospital exemption use of virus-specific T-lymphocytes in children: early experience within the Allovista clinical trial framework

Background Adoptive transfer of virus-specific T lymphocytes (VST) is an emerging strategy for refractory viral infections in immunocompromised individuals and is being prospectively evaluated in the ALLOVISTA clinical trial. Here we describe our experience with hospital-exemption advanced therapy medicinal product (ATMP-HE) VST in six pediatric transplant recipients. Methods Six children and adolescents (median age 4.5 years, range 2.5–18.5) treated in two Polish centers received VST for refractory viremia after allogeneic hematopoietic stem cell transplantation: adenovirus (ADV) in three cases, EBV-driven disease (EBV/PTLD or HL relapse with EBV reactivation) in three, including one patient with concomitant CMV/EBV/ADV infection. All patients had failed conventional antiviral and/or immunochemotherapy (cidofovir, rituximab, chemotherapy). VST were generated from allo-HSCT or related donors using automated CliniMACS Prodigy Cytokine Capture System (IFN-γ CCS, Miltenyi Biotec) following antigenic stimulation with viral peptide pools and released as ATMP-HE according to the ALLOVISTA protocol. A single intravenous infusion of 1.01×10 5 –1.85×10 6 VST (median 2.5×10 5 ) was administered. Virological response was assessed by quantitative PCR up to 4 weeks post-infusion, acute GVHD (aGVHD) and survival were recorded. Results Virological outcomes were evaluable in five patients. Four of five (80%) evaluated patients achieved at least a 1-log reduction in viral load, including two (40%) with complete clearance by week 4 (one EBV, one ADV). Two additional patients had marked but incomplete or transient viral load reductions, one patient showed minimal virological change. Despite biological activity, four children died: from progressive EBV disease (n=1), ADV infection (n=1), relapse of HL (n=1) and multi-organ failure with invasive fungal disease in a child with multi-viral infection (n=1). Two patients with complete virological responses are alive with sustained remission of viremia at the last follow-up. No new-onset or worsening aGVHD was documented after VST infusion. Conclusions VST administered as an ATMP-HE are feasible in routine clinical practice and demonstrate rapid antiviral activity in heavily pretreated pediatric patients. However, advanced viral disease and competing complications limit overall survival, underscoring the need for earlier intervention and advocating for treatment within the ongoing ALLOVISTA trial.