Venous thromboembolism during systemic inflammatory and autoimmune diseases associated with myelodysplastic syndromes, chronic myelomonocytic leukaemia and myelodysplastic/myeloproliferative neoplasms: a French multicentre retrospective case-control study.

OBJECTIVES: Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML) are associated with systemic inflammatory and autoimmune diseases (SIADs) in 10-30% of cases. The aims of this study were (i) to evaluate the prevalence of venous thromboembolism VTE in patients presenting with both MDS/CMML and SIADs, (ii) to describe risk factors associated with thrombosis, and (iii) to analyse the impact of VTE on overall survival and transformation to acute myeloid leukaemia in comparison to patients with MDS/CMML-associated SIADs without VTE. METHODS: This retrospective multicentre case-control study was conducted among patients with MDS/CMML and dysimmune disorders and featured in the French retrospective database of the French Network of Dysimmune Disorders Associated with Hemopathies (MINHEMON), diagnosed with MDS/CMML and dysimmune disorders. RESULTS: During a median follow-up of 16 months (5-48) VTE occurred in 35 patients (21.6 %) whereas 127 patients did not. Among those with VTE, 8 patients (22.9%) experienced two or more VTE. Common prothrombotic risk factors were not significantly different in patients with or without VTE. CMML was more frequent in patients without VTE (37 % vs. 14.3%, p=0.01), whereas myelodysplasic/myeloproliferative neoplasm (MDS/MPN) was higher in VTE patients (20 % vs. 5.5 %, p=0.01). In a multivariate analysis, only MDS/CMML progression at the time of VTE (odds ratio 28.82, 95 % CI (5.52-530.70) was significantly associated with VTE. When treated with an anticoagulation therapy, bleeding occurred in 19.4% of cases (6/31). Overall survival was not significantly different between patients with and without VTE (p=0.68). Leukaemia-free survival between groups was not significantly different (p=0.83). CONCLUSIONS: VTE is a common complication in MDS/CMML-associated SIADSs with an increased risk of bleeding when treated by anticoagulants. In the MDS/CMML subgroup, SIADS flares and MDS/CMML progression seem to be prothrombotic risk factors.

Rituximab maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis.

OBJECTIVE: To evaluate the efficacy compared to the relapse risk and tolerance of systematic rituximab (RTX) infusions as maintenance therapy for patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), who entered remission taking conventional immunosuppressants or RTX. METHODS: A retrospective study of the main clinical characteristics, outcomes, and RTX tolerance of patients who had received ≥ 2 RTX maintenance infusions in our center, regardless of induction regimen, between 2003 and 2010. RESULTS: We identified 28 patients [4 MPA and 24 GPA; median age 55.5 yrs (range 18-78); 17 (60%) males] who received a median of 4 (range 2-10) RTX maintenance infusions, with median followup of 38 months (range 21-97) since diagnosis or last flare. None experienced a RTX infusion-related adverse event; 15 patients (among the 21 with available data) had hypogammaglobulinemia (predominantly IgM) prior to their last RTX maintenance infusion; 3 had infectious events (1 cutaneous abscess, 1 otitis, 1 fatal H1N1 flu). Two patients suffered pulmonary relapses shortly before a planned RTX maintenance infusion (both had increased antineutrophil cytoplasmic antibody levels and 1 had CD19+ lymphocyte reconstitution). CONCLUSION: Rituximab maintenance therapy was well tolerated but did not completely prevent relapses and persistent "grumbling" disease. These preliminary results remain to be confirmed by a randomized controlled trial currently in progress.