Immunotherapy by allogeneic stem cell transplantation.
During the past three decades, allogeneic stem cell transplantation (ASCT) has developed from being an experimental therapy in patients with endstage leukemia into a well-established therapy in patients with a range of disorders of the immunohematopoietic system. Graft-versus-host disease (GVHD), acute or chronic, attacking host tissue is a major threat. However, donor immunocompetent T cells have a potent graft-versus-leukemia effect. A combination of calcineurin inhibitors and methotrexate is the standard therapy to prevent GVHD. Modulation of the immunosuppressive regimen may induce mild acute and mild chronic GVHD, reduce the risk of relapse, and improve long-term survival. Natural killer cells also play a role in this context. Killer cell immunoglobulin-like receptor incompatibility between recipient and donor may reduce the risk of relapse in patients with myeloid leukemia. Relapse of leukemia is a major cause of death after ASCT. Minimal residual disease and recipient leukemia lineage-specific chimerism are sensitive techniques for early detection of leukemic relapse. Donor lymphocyte infusions can enhance the antitumor effect, especially for patients with molecular relapse. The allogeneic graft-versus-cancer effect has been demonstrated in patients with metastatic breast, renal, colorectal, ovarian, prostatic, and pancreatic carcinoma. Mesenchymal stem cells have immunomodulatory properties and may be used for immunomodulation of GVHD and tissue repair. All things considered, the future looks promising for ASCT.
Ringdén
Olle
O
Division of Clinical Immunology, Karolinska Institutet, Karolinska University, Hospital, Huddinge, SE-141 86 Stockholm, Sweden.
D000818:Animals; D003131:Combined Modality Therapy; D005544:Forecasting; D015321:Gene Rearrangement; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D020544:Graft vs Leukemia Effect; D020350:Graft vs Tumor Effect; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods*; D007938:Leukemia / Q000601:surgery / Q000628:therapy; D016031:Liver Transplantation; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods; D051379:Mice; D018365:Neoplasm, Residual; D009369:Neoplasms / Q000601:surgery / Q000628:therapy; D012008:Recurrence; D033581:Stem Cell Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents