Low-Dose Methotrexate Toxicity Presenting as Pancytopenia

Abstract

High-dose methotrexate (MTX, 5 g/week) is typically used for the treatment of different malignancies and may be associated with serious side effects, such as acute kidney injury, myelosuppression, and hepatotoxicity. On the other hand, low-dose MTX (10-25 mg/week) is considered to be a safe and effective treatment for autoimmune arthropathies. Toxicity due to low-dose MTX is rare but can present with serious complications, such as pancytopenia.In this report, we present the case of an 82-year-old woman who presented with low-dose, MTX-induced severe pancytopenia and was treated with leucovorin rescue therapy with granulocyte colony-stimulating factor (G-CSF) therapy.

The Unseen Danger of Methotrexate Toxicity

“… 6 Methotrexate accumulates intracellularly and exerts its toxic effect despite the serum levels within normal range. 7 , 8 …”

Hypoplastic Myelodysplastic Syndrome: Symptom of Methotrexate Toxicity in Rheumatoid Arthritis

“…There are no specific guidelines for effectively treating MTX-induced pancytopenia. However, the treatment strategies that are being used are primarily directed at the reversal of the methotrexate-related toxic effects and its maintenance by continuous monitoring of the plasma concentrations of the drug [ 10 ]. This can be achieved by abrupt withdrawal of methotrexate and simultaneously adding anti-folic acid antagonist and synthetic colony-stimulating factors.…”

“…Leucovorin is an antidote for anti-folic acid agents, as it plays a significant role in reversing MTX-induced myelosuppression. Likewise, a review by Dhillon et al [ 10 ] found that adding filgrastim (a colony-stimulating factor) improves cell count in febrile neutropenia. The dosage regimen was as follows: folinic acid as 15 mg dose I/V, 6 hourly and filgrastim as 150 mg S/C, 12 hourly.…”

Fármacos antirreumáticos modificadores de la enfermedad convencionales y biológicos en enfermedad renal crónica y hemodiálisis

“…La eliminación principal del medicamento ocurre a través de la vía renal, donde aproximadamente el 80-90% se excreta sin modificaciones a través de la orina. Esta característica explica por qué cualquier reducción en la TFG conlleva un aumento en los niveles séricos del medicamento y, por ende, un mayor riesgo de mielotoxicidad (11). El MTX está contraindicado cuando la TFG es menor a 30 ml/min, si la TFG se encuentra entre 30-59 ml/min se recomienda una dosis inicial más baja (7.5-10 mg semanales).…”