Mitomycin C test for diagnostic differentiation of idiopathic aplastic anemia and Fanconi anemia

A cytogenetic test was developed to enable the diagnostic differentiation between Fanconi anemia and the group of disorders classified as "idiopathic" aplastic anemia. The method is based on the effect of the bifunctional alkylating agent mitomycin C (MMC) on chromosomes of peripheral lymphocytes in culture 92 to 96 hours. At the highest concentration of 80 ng/ml of MMC, about a 50-fold increase of chromosomal breaks and a 200-fold increase of radial figures was observed in Fanconi anemia lymphocytes in comparison with the average values for aplastic anemia cells or cells of healthy control subjects. In addition, sister chromatoid exchange analysis of cells treated with MMC demonstrated a marked inhibition of mitotic activity of lymphocytes of patients with increased sensitivity to MMC. It is advocated that the MMC-stress test should be used in each case of pancytopenia, as part of the therapy planning. The cytoreduction regimens used prior to bone marrow transplantation may produce lethal complications in patients with high clastogenic response to MMC.