Adoptive transfer of third-party donor CMV-specific T cells for refractory cytomegalovirus infection following umbilical cord blood transplantation.

Refractory cytomegalovirus (CMV) infection is a severe complication following umbilical cord blood transplantation (UCBT). Antiviral agents, the standard first-line therapy, are limited by toxicity and resistance without robust T-cell immunity. We evaluated third-party donor (TPD)-derived CMV-specific T cells (CMVSTs) as a treatment option. In a prospective phase I trial, UCBT recipients under 60 years with refractory CMV infection were enrolled. CMV-seropositive TPDs, matched for at least one human leucocyte antigen (HLA) class I allele at high resolution, were selected from family members. CMVSTs were manufactured for two infusions within 1 month. Safety and feasibility were primary end-points while efficacy and immune reconstitution were secondary end-points. Ten patients (median age: 15.5 years, range: 3-46 years) received CMVSTs (median doses: 2.2 × 10⁷/m² and 4.2 × 10⁷/m²). Products showed high CD3⁺ T-cell purity and memory T-cell dominance. Infusions caused mild adverse events, with no severe toxicities. At 6 months post-first infusion, 80% (8/10) achieved durable virological clearance; 60% (6/10) survived at 2 years with sustained CMV control. TPD-derived CMVST infusions are safe and feasible for refractory CMV infection post-UCBT, offering durable virological control while larger studies are needed to confirm efficacy. This trial was registered at www.chictr.org.cn as # ChiCTR2000034951.