Autoimmune rheumatological disorders and mutation profile of concomitant myelodysplastic syndrome.

Background: Association of autoimmune rheumatological disorders (AIRD) with myelodysplastic syndrome (MDS) and therapy-replated myeloid disorders (t-MN) have been reported with the prevalence of AIRD ranging from 10% to 48%. Immunosuppressive treatment of AIRD could cause therapy-related myeloid neoplasm (t-MN) or confound the secondary diagnosis of MDS. This study aims to investigate two large multi-institutional databases – Royal Adelaide Hospital Rheumatology Database (RAH-RD) and South Australian MDS (SA-MDS) registry to describe the association of AIRD and concomitant MDS.

Methods: Demographic, clinical, laboratory and treatment data of 2663 patients from RAH-RD and 1157 patients from SA-MDS were analysed. Patients with persistent cytopenia (>6 months) were defined as follows: haemoglobin <100 g/dL, absolute neutrophil <1800/mm3 and platelet <100,000/mm3.

Results: From RAH-RD database, 36 (1.3%) patients had at least one cytopenia with anaemia (19/36) being the most common, followed by neutropenia (8/36), thrombocytopenia (4/36) and bi-cytopenia (5/36). 23 patients had bone marrow examination, with 7 being consistent with MDS and 16 being non-diagnostic. Interestingly, 5 patients diagnosed with MDS and 11 patients with cytopenia did not receive any cytotoxic agents.

Analysis of the SA-MDS database revealed that 69 patients (5.4%) were diagnosed with AIRD. Among the 69 patients, 24 had low risk MDS and 15 had higher risk MDS, 19 had t-MN, 8 had MDS/MPN and 3 had AML. Overall, in a combined population of RAH-RD and SA-MDS, 76 (2%) had concomitant MDS and AIRD.

The cytogenetic and mutational profile of MDS patients with (n = 20) or without (n = 217) AIRD were compared. There is higher frequency of IDH1 mutations in MDS patients with AIRD compared to MDS without AIRD (30% vs 3%, P = 0.04).

Conclusions: 1.3% patients developed persistent cytopenia with 0.3% diagnosed with MDS. This finding is higher than the incidence of MDS in the general population (0.03–0.05%). Our findings warrant further study and may have implications for conventional treatment options for AIRD.