Studies on Levamisole - Induced

Widespread clinical trials of leavo-tetramisole (levamisole) as an immunopotentiating agent in rheumatoid arthritis. metastatic carcinoma, and immunodeficiency states have been complicated by agranulocytosis (AGC) in 2.5%-i 3% of patients. Other than a relationship with prolonged high dosage, very little is known regarding the pathogenesis of levamisole-induced AGC. Whereas leukoagglutination was negative, fluorochromatic microgranulocytotoxicity (GCY) tests were positive with serum from i 0 of i 0 acutely neutropenic patients. The antibody was 1gM, reacted with i 00% of unrelated granulocytes. but not with I or B lymphocytes. Some sera also reacted with monocytes and the myeloid cell line. K-562. Tests for antigen-antibody complexes or cold autoantibodies were negative. Although clinical evidence strongly suggests a haptene (drug) mechanism, in vitro mixing experiments were also negative. An alternative choice parallels the model of aldomet-induced Coombs’-positive hemolytic anemia. Finally, GCY first became positive 2-3 mo prior to the onset of AGC in two patients. suggesting the possibility of identifying those at risk well before the onset of neutropenia.