The influence of high-dose methotrexate therapy on serum iron.

After 43 cycles of high-dose methotrexate (MTX), the behavior of serum iron was determined. In virtually all cases, typical changes were demonstrated: 8-12 h after termination of treatment there was a sharp increase in serum iron. After 48-60 h, maximum values of 295% (median) of the pretreatment levels were found. Only when the serum MTX had dropped to 6.6 X 10(-8) M, after 62 h (median), did the serum iron level begin to drop; 72 h after termination of treatment the serum iron level had returned to the pretreatment level in only one, and after 108 h, only in 50% of the patients. The marked and persistent rise in serum iron must be considered a consequence of a powerful inhibitory effect of high-dose methotrexate on erythropoiesis. A possible explanation for the particular sensitivity of erythropoiesis to MTX may be the marked storage of MTX, and in particular MTX polyglutamates, in mature erythrocytes and their progenitor cells.