Monoclonal antibodies in the treatment of steroid-resistant acute graft-versus-host disease.
Acute graft-versus-host disease (GVHD) remains the major obstacle for successful allogeneic bone marrow transplantation (BMT). The frequency of grade II or higher acute GVHD ranges from 30-50% in human leukocyte antigen (HLA)-matched sibling transplants and 50-80% in HLA-matched unrelated transplants. The mortality and morbidity associated with this complication are substantial. Corticosteroid and polyclonal antibodies such as antithymocyte globulin (ATG) have had little success in treating the disease; however, advances have been made in hybridoma technology and understanding its immunopathophysiology. Based on these new insights, monoclonal antibodies, either murine or "humanized," were tested as rescue treatment for acute GVHD in human trials. Complete response rates ranged from 20-40%, with relapse occurring often. Side effects consisted of constitutional symptoms such as fever, chills, hypotension, thrombocytopenia, and leukopenia. Limitations of monoclonal antibody treatment included low response rate and patient survival, high relapse rate, risk of infectious complication, and leukemic relapse. Future study should focus not only on improved side effects and efficacy of monoclonal antibodies but also on better patient survival.
Department of Pharmaceutical Services, UCLA Medical Center, Los Angeles, California 90095-1707, USA.
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D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D004351:Drug Resistance; D006086:Graft vs Host Disease / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents