Introduction
Partially-HLA matched VSTs are safe and effective after failure of at least two weeks standard antiviral therapy to resolve viral infection. In this phase I trial, we assessed their safety when administered earlier in the course of viral infection post-HSCT.
Methods
A cell bank of VSTs was established from G-CSF mobilised peripheral blood from healthy donors. After stimulation with peptide mixes, VSTs were selected by expression of CD137 and cultured with cytokines. HSCT recipients were treated with up to 4 doses of 2x107of VST/m2commencing within 7 days of initial treatment for viral reactivation.
Results
A total of 188 doses of VST were manufactured from 7 donors with 12 product manufacturing runs (CMV n=3, EBV n=4 and Adv n=5). Median virus specificity was 75% for CMV, 83% for EBV and 37% for Adv. Thirty HSCT recipients were treated with VSTs within 7 days of initial antiviral treatment for viral reactivation at a median of 55 days post-transplant. Data from 25 patients were available for analysis (CMV n=22, EBV n=2, Adv n=1). Median age was 58 (0-71). 18 patients received a single infusion, 6 received 2 and 1 received 4 infusions. There were no immediate infusion-related toxicities. 23/25 patients (92%) had complete viral clearance (CR), 2 had a partial response (PR). Median time to best viral response was 20 days. There were 5 deaths (refractory aGVHD in 2 patients, pulmonary veno-occlusive disease/CMV pneumonitis, relapse of haematological malignancy, and sepsis/aspiration pneumonia). Overall survival at a median 348 days follow up post-infusion (56-668) was 80%.
Conclusion
Early infusion of third-party donor partially HLA-matched VSTs for viral reactivation after HSCT is associated with no immediate toxicity, a low rate of graft-versus-host disease and complete viral clearance in 92% of recipients.