Ferrokinetics after high-dose methotrexate therapy

After high-dose methotrexate with doses ranging from 2-10 g/m2, ferrokinetics were performed in 11 patients with different tumors. Iron-III-citrate-59Fe was injected at methotrexate serum concentrations ranging between 2.7 x 10(-7) -1.3 x 10(-8) M. With MTX levels greater than or equal to 4.2 x 10(-8) M the plasma iron clearance was always retarded, and the plasma iron turnover was diminished in 5 of 6 patients with levels of 3.1-8.9 x 10(-8) M at the time of the injection. In all cases with MTX concentrations greater than or equal to 5 x 10(-8) M the 59Fe-utilization as the measure of effective erythropoiesis was reduced pathologically below normal range. These results show that the erythropoiesis resumes its normal extent even in case of normal methotrexate clearance only when the methotrexate serum concentrations have fallen down below 5 x 10(-8) and that erythropoiesis is more sensitive against methotrexate toxicity than the granulocytopoiesis.