Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplant: where we now stand.

The infusion of lymphocytes from the original marrow donor (donor lymphocyte infusion [DLI]) reinduces complete remission in a high percentage of patients with chronic myeloid leukemia (CML) who relapse after allogeneic stem cell transplant, and thus, is probably the best initial approach to their management. The major predictive factor for response is the disease stage at time of treatment, because patients in molecular or cytogenetic relapse fare better than those in hematologic relapse. Moreover, patients with a short interval between transplant and DLI have a higher probability of response than those with longer intervals. The durability of DLI-induced remissions has not yet been established, but they appear to be prolonged. The observation that DLI can be highly effective for patients in relapse has encouraged the recent development of new strategies designed to minimize the myeloablative regimen and exploit the immunotherapeutic component of the transplant. The principal complication associated with use of DLI is the occurrence of graft-versus-host disease (GVHD). Several approaches have been tested to reduce the incidence or impact of GVHD, based on the ex vivo depletion of alloreactive donor cells or the use of donor T cells transduced with a suicide gene. The incidence of GVHD can also be reduced by starting with low doses of donor cells and "escalating" subsequent doses as required. However, the identification of selective targets for leukemia-reactive immunity is probably the optimal strategy to resolve the problem of GVHD. Although currently minor histocompatibility antigens appear to be the most likely targets for DLI, several groups are focusing on the generation of leukemia-specific immunity. The results obtained by use of tumor-associated antigens presented by dendritic cells are encouraging and may lay the foundations for the use of adoptive immunotherapy in the autologous setting.