ALBERT

Description: Introduction. Whereas von Willebrand disease is the most common constitutional bleeding disorder, acquired von Willebrand syndrome (AVWS) is rare with an estimated prevalence between 0.04 to 0.5%(1). AVWS has been related in various pathophysiological conditions including cardiovascular diseases such as aortic stenosis, autoimmune and lymphoproliferative disorders. To our knowledge, the prevalence of AVWS in lymphoproliferative disorders has never been investigated. Methods. We conducted an observational monocentric prospective study in Caen university hospital to evaluate the incidence of AVWS in B cell chronic lymphoproliferative disorders (B-CLPD) and characterize its phenotype. Inclusion criteria were the presence of a BCLPD in patients with no personal or family history of bleeding. Every enrolled patients was tested for Biological parameters were measured including closure time, von Willebrand Antigen (VWF:Ag), ristocetin cofactor activity (VWF:RCo) and factor VIII procoagulant activity (FVIII:C). The bleeding phenotype was evaluated using Tossetto bleeding score(2). AVWS was suspected when patients presented a decrease of VWF:Ag and VWF:RCo and/or a VWF:RCo/VWF:Ag below 0.7. Results. A total of 147 patients were included with the following diagnosis: fifty five patients (37%) with chronic lymphocytic leukemia, 48 patients (33%) with monoclonal gammopathies of undetermined significance (MGUS), 22 patients (15 %) with non hodgkin B cell lymphoma, 9 patients (6 %) with multiple myeloma, 4 patients (3 %) with Waldenstrom macroglobulinemia and 9 patients with other B-CLPD. Closure times, with epinephrine and ADP, were prolonged for six patients (6/147, 4.1%) with median levels of VWF:Ag, VWF:RCo, FVIII:C and VWF:RCo/VWF:Ag ratio at 29.5 IU/dL [9-284], 11.4 IU/dL [1-140] , 42.5 [6-204] and 0.3 [0.04-0.84], respectively. Five of these 6 patients had MGUS and 1 patient presented a follicular lymphoma. Serum protein electrophoresis revealed a monoclonal component in 5 patients with a median concentration at 8.45 g/L [4.4-9.1]. Four out of these 6 patients presented mucocutaneous bleedings including menorragia, ecchymoses, epistaxis, gingival bleedings, post-operative bleedings and gastro intestinal bleedings. The median bleeding score of these six patients was 4.5 [-1 – 12]. In four patients, the biological phenotype was a type 2 von Willebrand disease, with decreased VWF:RCo/VWF:Ag ratio (

Description: Abstract 2841 Introduction: Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) characterized by bone marrow fibrosis, splenomegaly, cytopenias and constitutional symptoms. Ruxolitinib was recently approved by the FDA for the treatment of MF in the USA; its approval in Europe is still pending. However, EU patients may access to ruxolitinib through compassionate programs. In France, health authorities opened a compassionate patient-named program (Authorization for Temporary Utilization [ATU] program. Methods: 241 French patients (pts) with MF, including primary (PMF), post-polycythemia vera (PPV) and post-essential thrombocythemia (PET) MF were granted ruxolitinib therapy through ATU program, independently of their JAK2 mutational status, between April 15, 2011 and May 31, 2012. Physicians were asked to provide information on disease characteristics, treatment history, constitutional symptoms, spleen size, platelet and neutrophils count, as well as the ruxolitinib dose prescribed and adverse events (AE). Request forms had to be submitted at the time of initial application and every 3 months upon drug resupply or in case of treatment discontinuation. This analysis has been performed based on data available at baseline (n= 241), after 3 months (n= 101), 6 months (n= 57), 9 months (n= 21) and 12 months (n= 4). Results: In the entire cohort, 138 pts were men and 103 women. Median age was 68.3 years. 51.5% of pts had PMF, 22.8% PPV-MF and 23.8% PET-MF. 99.2% of pts had received ≥1 lines of therapy for MF prior to ruxolitinib (hydroxyurea: 56%; pipobroman: 15.4%; iMIDs: 13.7%; interferons: 13.7%; erythropoietins: 6.6%; spleen irradiation: 6.6%; anagrelide: 5.8%; corticosteroids: 4.9%). Despite these therapies, 93.7% had constitutional symptoms and 94.2% of patients presented a palpable splenomegaly (median 15 cm below costal margin) at inclusion. Efficacy: According to the baseline platelet count, ruxolitinib therapy was initiated at 15 mg BID in 132 pts (54.8%) or 20 mg BID in 103 pts (42.7%), or other doses in a minority of pts (n=6). Among the pts who were evaluable after 3 and 6 months of therapy, 96.5% and 90% presented a mean reduction in the spleen size (by palpation) by 47.2% and 46% from baseline, respectively. Constitutional symptoms resolved in 65.3% and 70.2% of pts at the aforementioned time points, respectively. In pts who completed 9 months follow-up (n=21), benefits in spleen size reduction and symptoms resolution were durable (95% and 71.4%). Safety: Since the beginning of the ruxolitinib ATU program, 83 pts presented at least one AE, including 27 pts with serious AE (SAE), with or without causal relationship to ruxolitinib therapy. AE, all grades, were essentially hematologic abnormalities (51.6%), gastro-intestinal 6.3%, cardiac 3.1%, musculoskeletal 3.1%, hepatic 2.3%, infection 2.3%. Dose adjustments were reported in 60 pts, mainly due to thrombocytopenia (n=36) and anemia (n=13). However, no patient discontinued ruxolitinib therapy because of cytopenia. Treatment was discontinued in 11 patients after a median duration of 2.6 months (range 0.3–7.9 months). Reasons for discontinuation were death (n=6), AE (n=2), inefficacy (n=2), and patient decision (n= 1). Conclusion: In this large, unselected population of heavily pretreated MF pts, ruxolitinib therapy appeared to be effective in treating both constitutional symptoms and splenomegaly, in line with previously reported efficacy in clinical trials. The safety profile seems also comparable. Comprehensive data and updated follow-up of the cohort will be presented. Disclosures: Off Label Use: compassionate use of ruxolitinib for myélofibrosis in France (indication not yet approved by EMEA). Rey:Novartis: Consultancy. Nicolini:novartis, Bristol myers Squibb, Pfizer, Ariad and Teva: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Recher:Celgène, Genzyme, Sunesis, Jansen-Cilag: Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel to ASH Other. Ranta:Novartis: Membership on an entity's Board of Directors or advisory committees. Legros:Novartis, Bristol Myers-Squibb: Research Funding, Speakers Bureau, Travel to meeting Other. Viallard:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dupriez:novartis: Membership on an entity's Board of Directors or advisory committees. Coiteux:Novartis, Bristol Myers-Squibb: Speakers Bureau. Demory:Novartis: Honoraria. Giraudier:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ugo:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Travel to ASH Other. Kiladjian:Incyte: Membership on an entity's Board of Directors or advisory committees; Shire: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding. Roy:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Travel to ASH Other.