Multivirus-specific T Cells in the Treatment of Refractory CMV and/or EBV Infection After Allo-HSCT

An Exploratory Clinical Study of Multivirus-specific T Cells in the Treatment of Refractory Cytomegalovirus and/or Epstein-Barr Virus Infection After Allogeneic Hematopoietic Stem Cell Transplantation

To evaluate the safety and tolerability of partial HLA-matched VSTs against both CMV and EBV viruses in recipients of allogeneic hematopoietic stem cells with refractory viral infections (CMV and/or EBV).

Preliminary evaluation of the efficacy of partial HLA-matched VSTs against both CMV and EBV viruses in recipients of allogeneic hematopoietic stem cells with refractory viral infections (CMV and/or EBV); To monitor the duration and expansion of multi-virus VSTs cells after infusion.

This study consists of two parts: (1) The first stage is the safety evaluation of multi-virus VSTs and the exploration of DLT and MTD; (2) The second phase is to evaluate the safety and efficacy of multi-viral VSTs in selecting appropriate doses in the first phase.

Inclusion Criteria:

• Age ≥18 years old, and less than or equal to 70 years old, gender is not limited.
• Prior myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplantation.
• Persistent infection with CMV and/or EBV persists despite standard treatment .
• Prednisone or its equivalent hormone is less than or equal to 0.5 mg/kg/ day when enrolled.
• ECOG score ≤3, expected survival greater than 3 months.
• End blood oxygen saturation ≥90% on room air.
• Available multi-virus-specific cytotoxic T lymphocytes.
• Negative pregnancy test in female patients if applicable.
• Written informed consent and/or signed assent line from patient, parent or guardian.

Exclusion Criteria:

• Within 28 days after allogeneic hematopoietic stem cell transplantation.
• Active III-IV acute GVHD, and/or moderate and above chronic GVHD.
• Severe organ dysfunction: Heart: New York Heart Association (NYHA) levels III and IV; Liver: Total bilirubin>34umol/l; ALT, AST>2 times the normal upper limit; Kidney: Blood creatinine >130umol/L; Lung: Type I or II respiratory failure; Brain: unconsciousness, intracranial hypertension.
• Received DLI, other CTL, CAR-T, NK and other cell therapies, T cell monoclonal antibody immunosuppressants, or participated in any other clinical research related to drugs and medical devices within 28 days before enrollment.
• Poor compliance, and subjects deemed unsuitable for study participation by the investigator.