MYELODYSPLASTIC SYNDROMES AND ACUTE MYELOID-LEUKEMIA IN CONNECTIVE-TISSUE DISEASE AFTER SINGLE-AGENT CHEMOTHERAPY

Cytopenias are typical of patients with connective tissue disease (CTD ) and are usually related to autoimmune phenomena. In some cases, cyto penia may be tile result of treatment with cytotoxic agents. Although multi-drug therapy is known to produce myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) in patients with CTD, treatment with single-agent therapy, particularly methotrexate, has rarely been asso ciated with secondary MDS or AML. Blood and marrow samples were studie d from 3 men and 5 women with rheumatoid arthritis (5 cases), Behcet's disease (2 cases), and systemic lupus erythematosus (1 case) developi ng MDS or ARIL after methotrexate (5 cases), chlorambucil(2 cases), an d cytoxan(1 case). The durations of CTD ranged from less than 5 months to more than 10 years. Five patients (63%) presented with MDS includi ng refractory anemia (RA), refractory thrombocytopenia (RT), refractor y anemia with excess blasts (RAEB), chronic myelomonocytic leukemia (C MML), and RAEB in transformation. Patients with RT, CMML, and RAEB in transformation developed AML. Of six patients presenting with or devel oping AML, four had AML with differentiation (FAB M2), one acute myelo monocytic leukemia (FAB M4), and one M4Eo, Inv 16 was seen in the M4Eo and t(8; 21) in one case of M2. Four of six patients are alive up to 6 rears after diagnosis of AML. One of three patients with MDS is aliv e 6 months after diagnosis of MDS, Cytopenias in patients with CTD may be due to therapy-related MDS or AML occurring in a setting of single -agent chemotherapy, including methotrexate.