Relevance of in vitro studies of drug-induced agranulocytosis. Report of 14 cases.

Bone marrow colony forming unit-granulocyte macrophage (CFU-GM) cultures of 14 patients after neutrophil recovery from drug-induced agranulocytosis (median 12 weeks) were performed in the presence of 20 different drugs and/or acute-phase serum (APS) obtained during agranulocytosis. In 10 cases, drugs involved in agranulocytosis in vivo caused a significant inhibition of CFU-GM growth in vitro in comparison with normal cultures without drug. Three types of direct toxicity are suggested: (i) a decrease in the rate of mitosis; (ii) a destruction of cells (cytotoxic effect); or (iii) a blockage in progenitor mitosis (cytostatic effect). A humoral mechanism was suggested in 1 case because of enhanced inhibition with APS. In 4 cases no effect of the suspected drug could be detected by in vitro studies, but all hypotheses have not been tested in these cases, particularly the possible role of APS and other substances.