THU0264 MYELOID MALIGNANCIES, SYSTEMIC AUTOIMMUNE DISEASES AND CARDIOVASCULAR RISK: AN UNDER-REPORTED ASSOCIATION?
Authors: F. Ferro, C. Baratè, E. Elefante, F. Ricci, S. Balducci, G. Governato, G. Fulvio, M. Mosca, M. Petrini, S. Galimberti, C. Baldini
Journal: Annals of the Rheumatic Diseases (2020)

Background: The association between systemic autoimmune diseases (ADs) and lymphoproliferative malignancies is well established; nonetheless, few studies have investigated the prevalence and prognostic impact of myeloid malignancies on systemic autoimmune conditions. Objectives: To investigate the frequency of myeloid malignancies (i.e myelodysplastic syndrome (MDS) and chronic, either Philadelphia-positive or Philadelphia-negative, myeloproliferative disorders (MPNs)) in patients with ADs and their influence on the ADs clinical course and vice-versa. Methods: A retrospective systematic search through the electronic health records of the patients admitted at our Rheumatology University Hospital from 2009 and 2019 was performed to select those presenting with ADs and MDS or MPNs. To refine the search the ICD-9-CM diagnosis codes for MDS/MPNs were utilized. Medical charts of eligible patients were retrieved and data were collected with regard to demographics, type of AD, AD duration, prior treatments, serum laboratory indices, bone marrow aspiration and biopsy data. Categorical variables were compared using chi square test and Fisher’s test; continuous variables were compared using Student’s t-test. A 2-tailed value of p &lt;0.05 was taken to indicate statistical significance. Results: Out of the medical records of 5040 patients, we identified 51 patients (31 F: 20 M, mean age: 61 years (15)) with AD and myeloid malignancies: 17/51 with AD and MDS and 34/51 with AD and MPNs. No demographic differences were observed in the two subgroups. Regarding MDS, anaemia was the most common haematologic presenting finding (15/17, 88%), while the most common diagnosis was refractory anemia with excess of blasts (RAEB I/II) (5/17, 29%) followed by sideroblastic anemia (2/17, 12%). In the MPNs subgroup, 12/34 patients (35%) had a diagnosis of chronic myeloid leukemia (CML), 9/34 (26%) had a myelofibrosis (MF), 7/34 (21%) had an essential thrombocythemia (ET) and 6/34 (18%) had a polycythemia vera (PV). The JAK2 V617F mutation was detected in 100%, 57%, and 66% of PV, ET, and MF patients. Regarding the temporal appearance of myeloid malignancy, MDS occurred concurrently (9/17) or followed (7/17) the diagnosis of ADs in the vast majority of the cases whereas MPNs generally preceded the diagnosis of ADs (19/34). In MDS the most commonly diagnosed ADs were seronegative arthritis (5/17, 29 %), large and small vessel vasculitis (4/17, 23%) and Systemic Lupus Erythematosus (3/17, 17%). In patients with MPNs the diagnosis of rheumatoid arthritis (2/9, 22%), and antiphospholipid syndrome (3/9, 33%) were often associated with MF, whereas anti-Ro52 (TRIM21) positive systemic connective tissue disorders (4/7, 57%) were more frequently detected in ET. Cardiovascular events were observed in 14/51 (27%): 4/17 (23%) in MDS, 3/12 (25%) in CML and 7/22 (32%) in Philadelphia-negative MPNs. The latter seven cardiovascular events were all observed in patients presenting JAK2 V617F mutation (p=0.05). Conclusion: Our study is limited by its retrospective design. However, our results documented that the frequency of MDS and MPNs in ADs is not negligible and might be considered in the assessment of cardiovascular risk in systemic autoimmunity. Moreover, it has been reported that, under viral infection, TRIM21 is up-regulated by activation of the IFN/JAK/STAT pathway; interestingly, anti-Ro52 (TRIM21) were over-represented in MPN, where the JAK/STAT signal is hyper activated. This could explain also our observation that frequently the onset of ADs follows the diagnosis of MPN. Disclosure of Interests: Francesco Ferro: None declared, Claudia Baratè Speakers bureau: paid as a speaker by Jansen, Abbvie, Novartis, Amgen, Elena Elefante: None declared, Federica Ricci: None declared, Serena Balducci: None declared, Gianmaria Governato: None declared, Giovanni Fulvio: None declared, Marta Mosca: None declared, Mario Petrini Speakers bureau: paid as a speaker by Jansen, Abbvie, Novartis, Amgen, Sara galimberti Speakers bureau: paid as a speaker by Jansen, Abbvie, Novartis, Amgen, Chiara Baldini: None declared