Treatment of acute graft-versus-host disease with anti-CD3 monoclonal antibodies.
A dose-escalation trial was carried out to determine the efficacy and safety of using an IgG2a anti-CD3 monoclonal antibody to treat acute graft-v-host disease (GVHD) in marrow transplant recipients. Two patients received the antibody as the initial treatment of GVHD, and 22 patients received the antibody after failure of initial treatment with corticosteroids, cyclosporine, antithymocyte globulin (ATG), or combined ATG and cyclosporine. Antibody was administered at four dose levels, beginning at approximately 0.015 mg/kg/d and increasing by threefold increments. The initial doses of antibody were nearly always associated with fever and chills, and treatment had to be discontinued in one patient because of intolerable side effects. Improvement in skin disease could be reliably achieved at a dose of 0.15 mg/kg/d, but threefold higher doses appeared to be necessary for improvement in the liver or gut. In no case was there complete resolution of all manifestations of disease, and all patients surviving after antibody treatment required additional immunosuppressive treatment. Four patients developed Epstein-Barr virus (EBV)-associated lymphoproliferative disorders within seven to 18 days after starting antibody therapy. The overall risk of this complication in patients not given anti-CD3 monoclonal antibody is less than 1%. Anti-CD3 antibody represents an effective immunosuppressive agent for treatment of acute GVHD, but this treatment is associated with a substantial risk of EBV-associated lymphoproliferative disorders.
Martin
P J
PJ
Division of Clinical Research, University of Washington, Seattle.
Hansen
J A
JA
Anasetti
C
C
Zutter
M
M
Durnam
D
D
Storb
R
R
Thomas
E D
ED
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D017252:CD3 Complex / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D004306:Dose-Response Relationship, Immunologic; D004341:Drug Evaluation; D006086:Graft vs Host Disease / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000453:epidemiology / Q000209:etiology; D008875:Middle Aged; D013997:Time Factors
D000911:Antibodies, Monoclonal; D017252:CD3 Complex