The incidence of early-onset CMV disease occurring during the first 100 days post-transplant has been significantly reduced by the prophylactic or preemptive administration of ganciclovir to all CMV-seropositive patients and those receiving a transplant from an CMV-seropositive donor. This reduction in early-onset CMV disease has been achieved at the expense of an increase in late-onset CMV disease—occuring. 100 days post-transplant. Several risk factors for late-onset CMV disease have been described, such as a high viral load soon after the transplant, prolonged antiviral treatment prior to Day 1 100, and chronic GvHD. All these factors result in a delayed CMV-specific immune reconstitution post-transplant. Late CMV disease is associated with a high mortality, and is now the main CMV-associated problem that follows allogeneic stem-cell transplantation. An increased understanding of the mechanisms by which T cells recognize virus-and tumor-specific Ags has stimulated much interest in the use of specific T cells in adoptive immunotherapy for viral and malignant diseases. Unselected populations of lymphocytes from the peripheral blood of the seropositive donor usually contain virus-specific T cells and, as a result, can be used to control virus infection. However, the utility of such therapy is limited by potentially fatal complications that arise from alloreactive T cells also present in the donor lymphocyte infusion. A further problem of using unselected populations of donor lymphocytes is the rather low frequency of virus-specific T cells in the donor lymphocyte preparation.

Polyclonal populations of lymphocytes obtained from the peripheral blood of donors have been used successfully to treat the EBV-lymphoproliferative syndrome. However, the transfer of these unselected lymphocytes also caused GvHD. Enrichment of virus-specific lymphocytes by in vitro culture before transfer has been used to reduce the risk of GvHD.