Differential effect of high-dose methotrexate on erythropoiesis and granulocytopoiesis in humans.
The kinetics of erythroid and granulocytopoietic cell production were investigated during Courses 1 and 4 of high-dose methotrexate therapy with citrovorum factor rescue in a patient suffering from metastatic osteogenic sarcoma. Using the technique of quantitative 14C autoradiography, relative production rates were determined before, as well as 2, 24, 48, and 72 hr after, methotrexate infusion. There was only a minor decrease of the relative granulopoietic cell production 2 hr after methotrexate infusion followed by an overshoot reaction after 48 hr with a maximum of 3 to 4 times the pretherapeutic value. The relative erythropoietic cell production dropped to less than one-third of the pretherapeutic level during both courses and remained low during the period of postinfusion observation. The results indicate a severe and long-lasting impairment of the erythropoietic cell series, which is likely to include the committed stem cell pool. The impairment of granulocytopoiesis was much smaller and was followed quite soon by a reaction of recovery. The rate of DNA synthesis of individual cells was subnormal in all cell types investigated prior to Course 4 and was hardly affected by the methotrexate. Intracellular accumulation of methotrexate polyglutamates and differences in this pattern of accumulation between the red and white cell series are discussed as one possible explanation in this context.
D004247:DNA / Q000096:biosynthesis; D004920:Erythropoiesis / Q000187:drug effects*; D006098:Granulocytes / Q000187:drug effects*; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000378:metabolism / Q000633:toxicity*; D008875:Middle Aged
D004247:DNA; D008727:Methotrexate