Hematologic malignancies and the use of methotrexate in rheumatoid arthritis: a retrospective study

Am J Med. 1995 Sep;99(3):276-81. doi: 10.1016/s0002-9343(99)80160-0.


Purpose: To evaluate the relationship between use of methotrexate in rheumatoid arthritis patients and development of hematologic malignancies.

Patients and methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Review

MeSH terms

  • Adult
  • Aged
  • Arthritis, Rheumatoid / drug therapy*
  • Female
  • Hodgkin Disease / chemically induced
  • Humans
  • Lymphoma / chemically induced*
  • Lymphoma, Non-Hodgkin / chemically induced
  • Male
  • Methotrexate / adverse effects*
  • Methotrexate / therapeutic use
  • Middle Aged
  • Neoplasms, Second Primary / chemically induced*
  • Retrospective Studies


  • Methotrexate