Objective: Graft-versus-leukemia effects of donor lymphocytes have been considered to be central to the therapeutic benefit of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) for malignant diseases. Surprisingly, some patients who reject donor grafts following nonmyeloablative HCT have sustained remissions of advanced, chemorefractory hematologic malignancies. In murine mixed chimeras prepared with nonmyeloablative conditioning, we previously showed that recipient leukocyte infusions (RLIs) induce loss of donor chimerism and mediate antitumor responses against host-type tumors. We assessed the clinical relevance of our mouse model.
Methods: Mixed chimeric mice were generated by a nonmyeloablative protocol and some of them received host-derived tumor cells and/or RLIs or donor lymphocyte infusion (DLI). We examined chimerism, graft-versus-host disease (GVHD), and tumor survival.
Results: RLI is still effective when the leukocytes are obtained from tumor-bearing mice. Established mixed chimerism is required prior to the induced rejection to achieve maximum antitumor effects. The antitumor effects of RLI are not dependent on a specific donor strain or conditioning protocol. In contrast to DLI, RLI leads to donor cell rejection without the risk of GVHD.
Conclusion: Together, these data reinforce the clinical potential of RLI therapy as a new HCT strategy that does not carry the risk of GVHD.