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Ferrokinetics after high-dose methotrexate therapy.

A Schalhorn, H Sauer, W Wilmanns

    Klinische Wochenschrift
    |October 1, 1981
    PubMed
    Summary
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    High-dose methotrexate (MTX) significantly impacts iron metabolism and red blood cell production. Erythropoiesis is more sensitive to MTX toxicity than granulocytopoiesis, requiring MTX levels below 5 x 10(-8) M for recovery.

    Area of Science:

    • Hematology
    • Medical Oncology
    • Pharmacology

    Background:

    • High-dose methotrexate (MTX) is a critical chemotherapy agent used in various cancers.
    • Understanding MTX's impact on normal physiological processes like erythropoiesis is crucial for managing toxicity.
    • Ferrokinetics provides insights into iron metabolism and red blood cell production.

    Purpose of the Study:

    • To investigate the effects of high-dose methotrexate on ferrokinetics and erythropoiesis.
    • To determine the relationship between methotrexate serum concentrations and iron metabolism.
    • To assess the sensitivity of erythropoiesis to methotrexate toxicity.

    Main Methods:

    • Ferrokinetic studies were conducted in 11 cancer patients receiving high-dose methotrexate (2-10 g/m2).

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  • Iron-III-citrate-59Fe was administered during varying methotrexate serum concentrations (2.7 x 10(-7) -1.3 x 10(-8) M).
  • Measurements included plasma iron clearance, plasma iron turnover, and 59Fe-utilization.

    • Main Results:

    • Retarded plasma iron clearance and diminished plasma iron turnover were observed at MTX levels >= 4.2 x 10(-8) M.
    • Pathologically reduced 59Fe-utilization, indicating impaired erythropoiesis, occurred in all patients with MTX concentrations >= 5 x 10(-8) M.
    • Erythropoiesis recovery required MTX levels to fall below 5 x 10(-8) M, even with normal MTX clearance.

    Conclusions:

    • Erythropoiesis is significantly suppressed by high-dose methotrexate, with toxicity evident at serum concentrations >= 5 x 10(-8) M.
    • Erythropoiesis demonstrates greater sensitivity to methotrexate toxicity compared to granulocytopoiesis.
    • MTX serum concentration monitoring is essential for managing erythropoiesis suppression and optimizing cancer treatment outcomes.