To evaluate the relationship between use of methotrexate in rheumatoid arthritis patients and development of hematologic malignancies.
We retrospectively analyzed all patients registered at the Mayo Clinic from 1976 through 1992 with rheumatoid arthritis (n = 16,263) cross-indexed with patients registered during the same period with a hematologic malignancy (n = 21,270). Adult patients were selected who had rheumatoid arthritis, were treated with a disease-modifying antirheumatic drug, and subsequently developed a hematologic malignancy.
Thirty-nine patients met the selection criteria. Twelve of them had been given methotrexate. The characteristics of those who received methotrexate, including the type of hematologic malignancy, did not differ from those of patients who received other disease-modifying antirheumatic drugs.
Hematologic malignancies are uncommon in patients with rheumatoid arthritis treated with disease-modifying antirheumatic drugs, including methotrexate. There does not appear to be a relationship between the peak or cumulative dose or the duration of methotrexate therapy and the subsequent development of hematologic malignancy. The histologic types of hematologic malignancy seen in the methotrexate-treated patients did not differ from those of patients treated with other disease-modifying antirheumatic drugs.
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"Rheumatoid arthritis (RA) patients have an increased risk of developing lymphoma   . Since Ellman's first report  on lymphoma in a patient with RA who received low-dose methotrexate (MTX), the relationship between MTX medication and development of lymphoproliferative disorders (LPDs) has been widely discussed    . In 1993, Kamel et al.  reported that two patients taking MTX for rheumatologic disease, who developed lymphoma, were associated with Epstein-Barr virus (EBV) infection, and a spontaneous regression occurred after withdrawal of MTX. "
[Show abstract][Hide abstract] ABSTRACT: Patients with rheumatoid arthritis (RA) are known to develop lymphoproliferative disorders (LPDs) during the course of illness, particularly in cases treated with methotrexate (MTX) for long periods. We describe a case of MTX-related Epstein-Barr-virus-(EBV-) associated LPD resembling Hodgkin's lymphoma (HL), in which a dramatic complete remission was achieved after withdrawal of MTX coupled with clarithromycin (CAM) administration. Withdrawal of MTX coupled with CAM administration seemed to be effective for treating MTX-related EBV-associated LPDs. In particular, an immunomodulative effect of CAM might have been involved in achieving complete remission.