Autoimmune Disease (AD) in Patients with Myelodysplastic Syndrome (MDS): A Retrospective Single Institution Study.

Autoimmune disease (AD) can manifest uncommonly either at the time of diagnosis of MDS or during its course. When present, AD generally responds to immunosuppressive therapies, but cytopenias and immunosuppression associated with MDS compromise delivery of these therapies. Few studies have investigated the impact of co-existing AD on the course and outcome of patients with MDS. Our objective was to evaluate the clinical manifestations, laboratory characteristics, response to therapy and survival of MDS patients with AD. Records of patients evaluated at Roswell Park Cancer Institute with pathologically demonstrated MDS between 1993 and 2003 (n=277) were reviewed and patients with evidence of AD were identified. Patients with laboratory abnormalities without disease manifestations were excluded, as were patients with therapy-related MDS following treatment for AD. 13 patients (4%) were identified with co-existing MDS and AD. The initial presentation was AD in 6 (46%) and MDS in 4 (31%), while 3 patients (23%) had near-simultaneous diagnoses of both conditions. The spectrum of AD in these patients included systemic vasculitis in 3 patients, systemic lupus erythematosus in two and rheumatoid arthritis, temporal arteritis, cryoglobulinemia, aphthous stomatitis, pyoderma gangrenosum, inflammatory bowel disease, erythema nodosum and Evans syndrome in one patient each. Anti-double stranded DNA (levels ≥ 40.0 u/ml; normal range 0.0–3.5u/ml), ANA (≥1:160), cold agglutinins, low C3 and elevated ESR (≥100mm/hr) were the serological abnormalities detected at the time of AD diagnosis. Eleven of 13 patients were female, and median age at diagnosis of MDS was 65 years, while the entire cohort was 44% female (p=0.005) and had a median age of 71 yrs at diagnosis. FAB subtypes were RA (n=7), RAEB (n=3), CMMoL (n=2) and RARS (n=1). Cytogenetics were normal in 5 patients; abnormalities in the other 8 patients included −7, +8, and del(5q). The median survival of patients from diagnosis of MDS was 48 months and the survival from diagnosis of AD was 46 months. Known causes of death in 6 patients included sepsis, intracranial hemorrhage, lung cancer and transplant-associated multiorgan failure. Based on this study, AD occurs in 4% of MDS patients, predominantly affects female patients, and has heterogeneous clinical manifestations.The pathobiologic implication of the occurrence of AD at the same time or after the diagnosis of MDS is that the dysplastic clone might be responsible for the induction of immune dysregulation.