Cytomegalovirus (CMV) and Epstein Barr Virus (EBV) cause significant morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients in China. Antiviral drugs given either prophylactically or as early therapy for patients with detectable viral loads appear to be an effective strategy for reducing viral infections. However, long-term treatment with these drugs is associated with significant toxicity, expense and the appearance of drug resistant virus isolates ultimately resulting in treatment failure. CMV and EBV specific T cells infusion to immunocompromised patients following HSCT is able to induce a successful anti-viral response. The primary purpose of this study is to determine the safety and efficacy of the infusion of CMV and EBV specific cytotoxic T cells (CTLs) for patients with CMV and EBV reactivation or infection.

To generate CMV/EBV specific CTLs, G-CSF mobilized hemopoietic progenitor cell (G-HPC) products or nonmobilized peripheral blood apheresis collectings were stimulated with CMV/EBV specific peptides covering most HLA alleles among Chinese populations. Once the investigators made sufficient numbers of T cells, they tested their ex vivo properties.Then a fraction of CTLs were separated for immediate infusion and the others were frozen for further infusion.

If the donor was available, the donor derived CTLs were started to produce when CMV reactivation was detected by qPCR in recipients peripheral blood. Otherwise, autologous CTLs were used. For patients at high risk of developing CMV/EBV infections after stem cell transplantation, a small part of G-HPC products was extracted for CTLs generation.

Inclusion Criteria:

• Patients with any type of allogeneic HSCT
• CMV, adenovirus or EBV activation or infection which is defined as below. EBV/CMV reactivation is defined as CMV/EBV DNA levels > 1000 IU/ml for a single test or > 500 IU/ml for two consecutive tests. EBV/CMV related disease were defined as the demonstration of CMV/EBV biopsy specimen or clinical diagnosis through symptoms, signs or radiography.
• Written informed consent and/or signed assent line from patient, parent or guardian
• Positive CMV or EBV serology of the donor
• Absence of severe renal disease (Creatinine > 3x upper limit normal)
• Absence of severe hepatic disease (Bilirubin > 3x upper limit normal, AST > 3x upper limit normal)
• Life expectancy > 30 days

Exclusion Criteria:

• Active acute GVHD grades II-IV
• Received donor lymphocytes infusion(DLI) within 30 days
• Received ATG or other immunosuppressive monoclonal antibodies within 30 days
• Uncontrolled acute infections
• Active and relapse of malignancy
• Received steroids treatment more than 0.5 mg/kg/day prednisone