The immunobiology of T cell therapies for leukemias

Allogeneic bone marrow transplantation has revolutionized the treatment of chronic myelogenous leukemia, acute myeloid leukemia, and acute lymphocytic leukemia. Some of this success is due to the high doses of chemotherapy and radiotherapy allowable by rescuing fatal hematologic toxicity with the bone marrow allograft. However, it has become increasingly clear that an alloimmune antileukemic effect mediated by mature donor derived T cells, termed the graft-versus-leukemia reaction (GVL), makes a strong contribution to the efficacy of alloBMT. This has been dramatically illustrated by the complete remissions obtained in patients with relapsed leukemias after alloBMT following the infusion of donor mononuclear cells from their original marrow donors. In this review, after summarizing the clinical data in support of this effect, we discuss current paradigms of T cell mediated immunity and how they can be applied to explain the immunobiology of the GVL reaction.