Adoptive immunotherapy using donor leukocytes following bone marrow transplantation for chronic myeloid leukemia: is T cell dose important in determining biological response?

Overview

We investigated the use of donor leukocytes for the treatment of Epstein-Barr virus (EBV) lymphoproliferative disease following T cell-depleted bone marrow transplantation (BMT) for chronic myeloid leukemia (CML). We wanted to determine whether donor leukocyte treatment would result in altered biological responses with respect to anti-EBV lymphoma activity, donor-host chimerism and graft-versus-leukemia (GVL) responses. Three patients with CML in cytogenetic remission received < 10(6)/kg donor leukocytes for treatment of EBV lymphoproliferative disease. Lineage specific chimerism and residual leukemia detection were assessed using sensitive PCR methodologies. Following donor leukocyte treatment 1 patient had no recurrence and the other 2 had responsive EBV lymphoma. The 2 patients who were mixed T cell chimeras before treatment, remained so after treatment. Two were BCR-ABL positive by PCR before and after treatment and both developed hematologic relapse. None of the 3 patients developed acute graft-versus-host disease (GVHD) with 1 patient developing limited chronic GVHD. These data suggest that small numbers of donor T cells can eradicate EBV lymphoproliferative disease but may not alter donor-host chimerism or mediate GVL responses.