Safety and Efficacy of Donor-Derived Virus Specific Cytotoxic T Lymphocytes(CTL) Administered in Treatment for CMV/EBV Infections after Allogenetic Stem Cell Transplantation

Objective:

To investigate the safety and efficacy of donor-derived cytomegalovirus(CMV) specific cytotoxic T lymphocytes(CTL) and Epstein-Barr virus(EBV) specific cytotoxic T lymphocytes(CTL) as immune therapy in CMV viremia and EBV viremia postallogeneic transplant.

Methods:

A total of fifty-three patients receiving haplo-identical allogeneic HSCT for hematological malignancy were eligible for recruitment to the study from February 2013 to December 2015. Thirty-eitht patients of CMV viremia postallogeneic transplant received CMV CTL. Fifteen patients of EBV viremia postallogeneic transplant received EBV CTL. The criteria for inclusion were: (1) plasma CMV/EBV DNA >1×10³/ml. (2) Antiviral therapy (ganciclovir and foscaret) was not effective.(3) Antiviral therapy was not tolerated for pancytopenia. The criteria for exclusion were: (1) plasma CMV/EBV DNA <1×10³/ml. (2) Prophylactically administered CMV-specific T cells and EBV-specific T cell. T-cell infusion: Patients were infused with a single dose of 2-3×10⁵/kg weekly. Median number of infusion was 8(2-15). Criterion of therapeutical effect: Virus DNA copy number decreased by a log rank or above (Valid). Virus DNA copy number to zero(negative). Virus DNA copy number increased or not reduced ( Invalid).

Results:

38 cases of CMV viremia were effective in 28 cases, the effective rate was (73.7±7.1)%, the median onset time was 5 days (2-10). Plasma CMV was negative in 28 cases, the negative rate was (73.7±7.1)%, the median negative time was 11 days (2-24). 15 cases of EBV viremia were effective in 13 cases, the effective rate was (86.7±8.8)%, the median onset time was 5 days (2-11). Plasma EBV was negative in 13 cases, the negative rate was (86.7±8.8)%, the median negative time was 10 days (3-24). Adverse events: fever(n=1), skin rash(n=3), hypoxemia(n=2), diarrhea (n=1 uncertain), Tachycardia of sinus( n=1)

Conclusion:

Safety and efficacy of virus specific cytotoxic T lymphocytes(CTL) administered postallogenetic HSCT are exact. CTL can be used as second-line therapy of viral infections postallogenetic HSCT.