Adoptive immunotherapy for leukemia

Adoptive immunotherapy using allogencic lymphocytes requires a state of tolerance. Chimerism and tolerance can be induced by marrow transplantation, and in animals donor lymphocytes can be transfused after establishment of tolerance without producing graft-versus-host disease (GVHD). In human patients with recurrent leukemia after marrow transplantation remissions may be induced by transfusion of donor lymphocytes (DLT). The graft-versus-leukemia (GVL) effect of DLT is best in patients with CML in cytogenetic (72%) or hematological relapse (74%). It is less in AML/MDS (23%) and least in ALL (12%) without chemotherapy-induced remission. In CML cytogenetic responses may take several weeks to occur, molecular biologic responses often occur only after several months. Complete responses have been observed after DLT from matched unrelated donors and one HLA-antigen mismatched family donors, they have not been observed after DLT from monozygotic twin donors. In our analysis 40.5% of patients surviving 14 days after donor lymphocyte transfusions developed significant GVHD. Patients with GVHD of mild and moderate degree have higher response rates than patients without GVHD. 31% of patients with CML developed myelosuppression. It may be cured by the transfusion of donor marrow or stem cells. Dendritic cells are part of the CML clone, their involvement in other forms of leukemia is unknown. Presently, transfusion of peripheral blood stem cells as source of both dendritic cells and stem cells with and without intensive chemotherapy is studied.