Most Closely HLA-Matched CTLs for Relapsed Epstein Barr Virus(EBV)-Associated Diseases

First, we will search our cell bank to see if there is a CTL line that is a match with the subject and his/her donor. This matching is done using HLA type, which measures 6 proteins on the cell surface. If HLA type has not been previously checked, we will do a blood draw (half to one tablespoon) so that this can be done. These CTL lines have been made at Baylor College of Medicine from donors for other transplant patients or other normal donors from the National Marrow Donor Program. All donors have been screened in the same way that we screen blood donors. When the CTL lines were made, blood was taken from the donors and used to grow T cells. To do this, we first grew a special type of cells called dendritic cells or monocytes and we put a specially produced human virus (adenovirus) that carries the LMP genes into the dendritic cells or monocytes. They were then used to stimulate T cells. This stimulation trained the T cells to kill cells with LMP on their surface. We then grew these LMP specific CTLs by more stimulation with EBV infected cells (made from the same blood). We also put the adenovirus that carries the LMP genes into these EBV infected cells so that we increased the amount of LMP that these cells had. These EBV infected cells were treated with radiation so they could not grow. Once we made sufficient numbers of T cells, we tested them to make sure they kill cells with LMP on their surface and froze them. To make sure that these cells won't attack the subject's tissues, we will also test the cells against his/her own cells, which we will grow in the laboratory. If the level of circulating T-cells in the patient is relatively high, s/he will receive one treatment of cyclophosphamide. This drug will decrease the numbers of the patient's own T-cells before the investigators infuse the LMP-specific cytotoxic T-lymphocytes. If the patient is already receiving chemotherapy, this may not be needed. The LMP specific CTLs will be thawed and injected IV over 1-10 minutes. Initially, one dose of T-cells will be given. If after the first dose, there is a reduction in the size of the patient's disease, they can receive up to five additional doses of the T-cells if they wish. This is a dose escalation study, which means that the doses of cells will be increased as more patients are treated, as long as the lower doses are determined to be safe.