title: Myelodysplastic syndromes and acute myeloid leukemia in connective tissue disease after single-agent chemotherapy.
abstract: Cytopenias are typical of patients with connective tissue disease (CTD) and are usually related to autoimmune phenomena. In some cases, cytopenia may be the 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 associated with secondary MDS or AML. Blood and marrow samples were studied from 3 men and 5 women with rheumatoid arthritis (5 cases), Behcet's disease (2 cases), and systemic lupus erythematosus (1 case) developing MDS or AML after methotrexate (5 cases), chlorambucil (2 cases), and cytoxan (1 case). The durations of CTD ranged from less than 6 months to more than 10 years. Five patients (63%) presented with MDS including refractory anemia (RA), refractory thrombocytopenia (RT), refractory anemia with excess blasts (RAEB), chronic myelomonocytic leukemia (CMML), and RAEB in transformation. Patients with RT, CMML, and RAEB in transformation developed AML. Of six patients presenting with or developing AML, four had AML with differentiation (FAB M2), one acute myelomonocytic 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 years after diagnosis of AML. One of three patients with MDS is alive 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.
authors.affiliation: University Hospitals of Cleveland, Institute of Pathology, Case Western Reserve University, Ohio 44106-5077, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Rosenthal
authors.forename: D C
authors.initials: DC
authors.lastname: Farhi
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018501:Antirheumatic Agents / Q000009:adverse effects*; D002699:Chlorambucil / Q000009:adverse effects; D003240:Connective Tissue Diseases / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D003520:Cyclophosphamide / Q000009:adverse effects; D003582:Cytogenetics; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000150:complications / Q000209:etiology / Q000473:pathology*; D007970:Leukopenia / Q000209:etiology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000209:etiology / Q000473:pathology*
chemical_list: D015703:Antigens, CD; D018501:Antirheumatic Agents; D002699:Chlorambucil; D003520:Cyclophosphamide; D008727:Methotrexate