Cimetidine induced pancytopenia

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Abstract
We describe a 26 year-old male with a pancytopenia possibly due to cimetidine. Using progenitor cell culture techniques we investigated the mechanism of this bone marrow toxicity. Our results show a cimetidine dose-dependant inhibition of normal human CFU-GM colony formation as described by Fitchen and Koeffler in 1980 [15]. No differences in growth inhibition were found between the patients' recovery marrow and the controls. Toxicity on normal human CFU-MIX colony formation was, however, far more pronounced. At concentrations as low as 5µg/ml the numbers of CFU-MIX colonies were decreased by almost 20% and more than 30% in cultures of two normal bone marrow samples. A significant decrease in CFU-MIX colony size was measured even at therapeutic levels (0.5µg/ml). No obvious decrease in CFU-GM colony size was noticed at low concentrations. Experiments with T-cell- and monocyte-depleted bone marrow samples gave similar results: a pronounced inhibition of the CFU-MIX colony formation at low concentrations of cimetidine whereas the CFU-GM formation was less affected. It is therefore very unlikely that Accessory cells play part in the cimetidine induced CFU-MIX inhibition. Our results suggest the existence of H2 histamine receptors on human CFU-MIX (= multipotent progenitor cell). Blocking these receptors prevents the multipotent progenitor cell from going into the DNA-synthesis phase of the cell cycle.