Retrospective analysis of cases with low dose methotrexate-induced neutropenia

Objective: Low dosemethotrexate (MTX) is among the most commonly used drugs in rheumatology and rarely associated with neutropenia. It is generally observed as a result of improper use or in patients with risk factors for toxicity. This study aimed to demonstrate the clinical characteristics and short-term follow-up outcomes of patients who presented with neutropenia related to low-dose MTX therapy. Methods: Patients (>18 years) who were referred to our clinic due to neutropenia (neutrophil <1500/mm³) associated with low-dose MTX use between October 2022 and April 2024 were retrospectively analyzed. We recorded patients’ demographics, MTX dosage, risks for toxicity, laboratory and clinical findings at the time of presentation, the treatments, duration of recovery from neutropenia and mortality rates. Results: There were 9 patients followed for low-dose MTX-associated neutropenia; 6 were female, and the mean age was 71. Seven patients had pancytopenia. Improper high-dose (7.5-15 mg/d) usage was detected in 7 patients. Eight patients presented with mucositis, and 3 had febrile neutropenia. At presentation, mean leukocyte count was 1520/mm³, neutrophil count was 600/mm³, hemoglobin was 8.7 g/dL, and platelet count was 66000/mm³. All patients were started on intravenous leucovorin without granulocyte-colony stimulating factor treatment, and the mean time to improvement for neutropenia and leukopenia was 8 and 8.6 days, respectively. No cases of mortality were detected. Conclusions: In most of our casesMTX-associated neutropenia resulted from improper use. With leucovorin monotherapy and infection control, neutropenia improved within 8 days.