Graft-versus-leukemia effects of transplantation and donor lymphocytes.
Allogeneic transplantation of hematopoietic cells is an effective treatment of leukemia, even in advanced stages. Allogeneic lymphocytes produce a strong graft-versus-leukemia (GVL) effect, but the beneficial effect is limited by graft-versus-host disease (GVHD). Depletion of T cells abrogates GVHD and GVL effects. Delayed transfusion of donor lymphocytes into chimeras after T cell-depleted stem cell transplantation produces a GVL effect without necessarily producing GVHD. Chimerism and tolerance provide a platform for immunotherapy using donor lymphocytes. The allogeneic GVL effects vary from one disease to another, the stage of the disease, donor histocompatibility, the degree of chimerism, and additional treatment. Immunosuppressive therapy before donor lymphocyte transfusions may augment the effect as well as concomitant cytokine treatment. Possible target antigens are histocompatibility antigens and tumor-associated antigens. Immune escape of tumor cells and changes in the reactivity of T cells are to be considered. Durable responses may be the result of the elimination of leukemia stem cells or the establishment of a durable immune control on their progeny. Recently, we have learned from adoptive immunotherapy of viral diseases and HLA-haploidentical stem cell transplantation that T-cell memory may be essential for the effective treatment of leukemia and other malignancies.
Kolb
Hans-Jochem
HJ
Department of Medicine 3, Hematopoietic Cell Transplantation, University of Munich & Helmholtz Zentrum Muenchen-National Research Centre for Environmental Health, Munich, Germany. Hans.kolb@med.unimuenchen.de
D000970:Antineoplastic Agents / Q000627:therapeutic use; D001549:Benzamides; D001782:Blood Donors; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000401:mortality; D006087:Graft vs Host Reaction; D020544:Graft vs Leukemia Effect / Q000276:immunology* / Q000502:physiology; D006801:Humans; D000068877:Imatinib Mesylate; D007108:Immune Tolerance / Q000276:immunology; D016219:Immunotherapy, Adoptive / Q000009:adverse effects / Q000379:methods; D007938:Leukemia / Q000276:immunology / Q000401:mortality / Q000517:prevention & control / Q000628:therapy; D017710:Lymphocyte Transfusion / Q000009:adverse effects / Q000379:methods / Q000401:mortality; D008214:Lymphocytes / Q000276:immunology* / Q000502:physiology; D010879:Piperazines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D014181:Transplantation Immunology / Q000502:physiology; D019139:Tumor Escape / Q000276:immunology
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate