Myeloid neoplasms arising after methotrexate therapy for autoimmune rheumatological diseases do not exhibit poor-risk molecular features

TO THE EDITOR: Autoimmune diseases, including autoimmune rheumatic diseases (AIRD) are reported in 8–30% of patients with myeloid neoplasm (MN), including myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN), and may precede or follow autoimmune disease. Despite increased recognition of the association, causative factors remain unresolved, and clinical outcomes are not established. For example, the role of cytotoxic and disease-modifying antirheumatic drugs (DMARDs) in the development of MN remains uncertain. DMARDs can be broadly classified as cytotoxic, immunomodulatory, or biologic. High-dose methotrexate, cyclophosphamide, and azathioprine are considered cytotoxic DMARDs, although the low-dose methotrexate used for AIRDs is generally considered to have an anti-inflammatory rather than cytotoxic mechanism of action. Early reports suggested an increased incidence of MN following exposure to low-dose methotrexate, but this was not replicated in a recent case-control study. Increased incidence of MN following treatment with azathioprine and cyclophosphamide was reported. However, these studies did not investigate the genetic profiling of MN following exposure to methotrexate and other DMARDs...