Key Points• Treatment with PEG- in PV and ET results in a high rate of complete hematologic and molecular responses.• Patients failing to achieve complete molecular remission tended to have higher frequencies of mutations in genes other than JAK2.Pegylated interferon a-2a (PEG-IFN-a-2a) has previously been shown to induce hematologic and molecular responses in patients with polycythemia vera (PV) or essential thrombocythemia (ET). Here we present a follow-up of a phase 2 trial with PEG-IFN-a-2a treatment in 43 PV and 40 ET patients with detailed molecular analysis. After a median follow-up of 42 months, complete hematologic response was achieved in 76% of patients with PV and 77% of those with ET. This was accompanied by complete molecular response (CMR) (ie, undetectable JAK2V617F) in 18% and 17%, of PV and ET patients, respectively. Serial sequencing of TET2, ASXL1, EZH2, DNMT3A, and IDH1/2 revealed that patients failing to achieve CMR had a higher frequency of mutations outside the Janus kinase-signal transducer and activator of transcription pathway and were more likely to acquire new mutations during therapy. Patients with both JAK2V617F and TET2 mutations at therapy onset had a higher JAK2V617F mutant allele burden and a less significant reduction in JAK2V617F allele burden compared with JAK2 mutant/TET2 wildtype patients. These data demonstrate that PEG-IFN-a-2a induces sustained CMR in a subset of PV or ET patients, and that genotypic context may influence clinical and molecular response to PEG-IFN-a-2a. (Blood. 2013;122(6):893-901)

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Background:Myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasms (MDS/MPN) can be associated with vasculitis.Objectives:In this nationwide study by the “French Network of dysimmune disorders associated with hemopathies” (MINHEMON) the objective was to evaluate characteristics, treatment and outcome of vasculitis MDS-MDS/MPN.Methods:Retrospective analysis of patients that presented a MDS/MPN associated with vasculitis and compared the overall survival and acute leukemia with MDS without vasculitis.Results:Seventy patients with vasculitis and MDS/MPN were included, with a median age of 71.5 [21-90] years and male/female ratio of 2.3. Vasculitis was diagnosed prior to MDS/MPN in 31 patients (44.3%), with a median time of 27 months [1-120] between two diagnosis, and after in 20 patients (6 months [1-59]). In comparison to 183 MDS/MPN without dysimmune features showed no difference in MDS/MPN subtypes distribution nor median IPSS/CPSS scores in patients with and without vasculitis. The vasculitis subtypes was giant-cell arteritis (GCA) in 24 patients (34%). Eleven patients (20%) had Behçet’s-like syndrome and 6 patients (9%) presented with polyarteritis nodosa. Steroids (60 mg/day [0-500] of prednisone equivalent) were used as first-line therapy for MDS/MPN vasculitis in 64/70 patients (91%) and 41 (59%) received combined immunosuppressive therapies during the follow-up. After the follow-up of 33.2 months [1-162], 31 patients (44%) finally experienced sustained remission. At least one relapse during the 33.2 months [1-162] follow-up occurred in 43 patients (61%). Relapse rates were higher in patients treated by DMARDs (odds ratio at 4.86 [95% CI 1.38 - 17.10]), but did not differ from biologics (odds ratio 0.59 [95% CI 0.11-3.20]) and azacytidine (odds ratio 1.44 [95% CI 0.21-9.76]) (steroids considered as reference). Overall survival and progression to acute myeloid leukemia in MDS/MPN vasculitis were not significantly different from MDS/MPN patients without any dysimmune features (p=0.5).Conclusion:This first largest study of MDS/MPN vasculitis show no correlation of vasculitis subtypes with various subtypes and severity of MDS/MPN, and no significant impact of vasculitis on overall survival and progression to acute myeloid leukemia. The high relapse rats and steroid dependence raise the question of combined therapies to steroids. Whereas DMARDs use seem to be avoid specific azacytidine therapy could be considered for even low-risk MDS/MPN vasculitis.Acknowledgments:minhemon gfm gfevDisclosure of Interests:None declared

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