Donor lymphocyte infusions mediate superior graft-versus-leukemia effects in mixed compared to fully allogeneic chimeras: a critical role for host antigen–presenting cells

DOI PDF 被引用文献2件
  • Markus Y. Mapara
    From the Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, Boston; and Tufts University School of Veterinary Medicine, North Grafton, MA.
  • Yong-Mi Kim
    From the Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, Boston; and Tufts University School of Veterinary Medicine, North Grafton, MA.
  • Sheng-Ping Wang
    From the Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, Boston; and Tufts University School of Veterinary Medicine, North Grafton, MA.
  • Roderick Bronson
    From the Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, Boston; and Tufts University School of Veterinary Medicine, North Grafton, MA.
  • David H. Sachs
    From the Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, Boston; and Tufts University School of Veterinary Medicine, North Grafton, MA.
  • Megan Sykes
    From the Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital, Harvard Medical School, Boston; and Tufts University School of Veterinary Medicine, North Grafton, MA.

抄録

<jats:p>In mice, donor leukocyte infusion (DLI) given to established mixed allogeneic chimeras can mediate powerful graft-versus-host (GVH) reactions confined to the lymphohematopoietic system without inducing graft-versus-host disease (GVHD). In a clinical trial attempting to capture this approach to achieve graft-versus-leukemia/lymphoma (GVL) effects without GVHD, we have observed surprisingly powerful antitumor effects of DLI in patients achieving mixed chimerism after nonmyeloablative bone marrow transplantation. This observation led us to hypothesize that host antigen–presenting cells in mixed chimeras might be required to optimally present recipient antigens to the donor lymphocytes, leading to maximal graft-versus-tumor effects. To test this hypothesis, we established mixed and fully allogeneic hematopoietic chimeras in B6 mice and evaluated the effect of DLI on EL4 T-cell lymphoma. DLI administration to mixed chimeras produced dramatically improved leukemia-free survival compared to administration of DLI to full donor chimeras. DLI also converted mixed chimeras to full chimeras without causing GVHD. The magnitude of the GVL effect was dependent on the level of major histocompatibility complex class I expression on recipient hematopoietic cells in mixed chimeras. Thus, the induction of mixed chimerism followed by delayed DLI provides an approach to inhibiting GVHD that optimizes GVL effects.</jats:p>

収録刊行物

  • Blood

    Blood 100 (5), 1903-1909, 2002-09-01

    American Society of Hematology

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