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Prepublished online as a Blood First Edition Paper on September 4, 2003; DOI 10.1182/blood-2003-02-0342.
Submitted February 4, 2003
Accepted August 4, 2003
Graft-versus-leukemia reactions in allogeneic chimeras
Hans-Jochem Kolb*, Christoph Schmid, A John Barrett, and Dolores J Schendel
Department of Medicine III, Clinical University of Munich-Grosshadern, Munich, Germany; Clinical Cooperative Group: Hematopoietic Cell Transplantation, GSF-National Research Center for Environment and Health and the University of Munich, Munich, Germany
National Heart, Lung and Blood Institute, National Institute of Health, Bethesda, MD, USA
Institute of Molecular Immunology, GSF-National Research Center for Environment and Health, Munich, Germany
* Corresponding author; email: kolb{at}med3.med.uni-muenchen.de.
There is a strong graft-versus-leukemia (GVL) effect of allogeneic stem cell transplantation (SCT) due to elimination of tumor cells by alloimmune effector lymphocytes. When leukemia relapses after allogeneic SCT, donor lymphocyte transfusions (DLT) can induce sustained remis-sions in some patients. This review summarizes the current status on clinical use of DLT, the basis of GVL reactions, problems associated with this therapy, and new strategies to improve DLT. Several multi-center surveys demonstrated that the GVL effect of DLT is most effective in chronic myelogenous leukemia (CML), whereas it is less pronounced in acute leukemia and myeloma. Cytokine stimulation to induce differentiation of myeloid progenitor cells or to up-regulate costimulatory molecules on tumor cells may improve the efficacy of DLT. Infections and graft-versus-host disease (GVHD) are major complications of DLT. Control of GVHD may be improved using suicide gene-modified T cells for DLT, allowing T cell elimination if severe GVHD develops. Hopefully, in the future, GVL can be separated from GVHD through adoptive transfer of selected T cells that recognize leukemia-specific antigens or minor histocompatibility antigens, which are expressed predominantly on hematopoietic cells, thereby precluding attack of normal tissues. In patients with leukemia and lymphomas with fast progression, tumor growth may outpace development of effector T cells. Here it may be preferable to select SCT donors with HLA-mismatches that allow alloreactive natural killer cells, which appear early after trans-plantation, to retain their cytolytic function. New approaches for adoptive immune therapy of leukemia are being developed which promise a better prognosis for these patients.
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