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Background: Genetic factors play an important role in deep vein thrombosis (DVT). The duration of anticoagulation therapy in patients with verified genetic inheritance and previous events of DVT is still questionable. Case reports: We present three cases of siblings (two brothers and one sister) with verified Venous thromboembolism (VTE) and genetic inheritance. The first case is a 33 y.o. male who was admitted with bilateral massive pulmonary thromboembolism and DVT of the right femoral vein. He had an episode of DVT 4 years ago. Fibrinolytic therapy was introduced immediately. Afterwards, unfractionated heparin was introduced, and then switched to enoxaparin and acenocoumarol. Because of inappropriate INR, it was switched then to rivaroxaban. The imaging methods showed significant improvement, and the patient was discharged from the hospital with rivaroxaban at 2x15 mg/day for another 2 weeks and was instructed to continue 20 mg/day until his next control. In the meantime, the second case, a 36 y.o. male, brother to the first patient, came with vein thrombosis of vena saphena magna of the left leg. Treatment with Acenocoumarol was started and continued for 2 years until complete resolution of the thrombi, and then it was changed to Aspirin. The third case is the sister of the first 2 cases, a 38 y.o female with symptoms and findings almost similar to those in the second case. She was treated with Acenocoumarol for 6 months. Doppler ultrasound showed complete resolution of the thrombosis and anticoagulation therapy was stopped. Genetic investigations for mutation showed presence of homozygous gene mutation for Prothrombin (PTB G20210A) in the first patient, his brother (the second case) was compound heterozygote for PTB and for MTHFR C677T, and his sister (third case) was heterozygous only for the PTB mutation. According to the clinical (recurrent unprovoked DVT with thromboembolic complications) and genetic testing (homozygous gene mutation for PTB) in the first patient, we decided to continue the secondary thromboprophylaxis with rivaroxaban 10 mg/day indefinitely. Conclusion: Testing for genetically inherited thrombophilia should be included in the risk assessment for recurrence, and performed in all patients under 50 y.o. who have a first, non-provoked episode of thrombosis, in order to determine the duration of anticoagulation therapy.

Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed type of leukemia in Western Europe and North America, and represents about 30% of all leukemias in adults. CLL is a disease of elderly, who often have multiple comorbidities. These factors affect further treatment decisions, despite the great progress in the therapy of CLL in the last two decades. The aim of this study was to evaluate the current status in the management of patients with CLL in the Republic of Macedonia and to compare it with CLL patients in other western countries. We analyzed 102 patients with CLL referred to our Institution for control and/or treatment in the period from January 2015 to October 2015. Median age of our group of patients at the time of diagnosis was 62.7 years with almost 40% of patients older than 64 years. Male to female ratio was 1.3:1 and 54% of patients were diagnosed in stage “0” according to Rai staging system. Watch and wait was the most common treatment approach (58.8%) at the time of diagnosis, but at the moment of analysis only 33% of patients were still with-out treatment. The most common treatment in this group of CLL patients was FCR protocol with 39.5% of patients treated with an average of 5 cycles of this immunochemotherapeutic regimen. The average time of progression free survival (PFS) in all treated patients was 32.8 months with range between 2-72 months. In summary, clinical characteristics of CLL patient in our clinical settings and the most common therapeutic approach at our Institution do not differ significantly from the characteristics of the average CLL patient in other studies.

© 2018 The Authors., [Background]: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. [Patients and Methods]: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months., [Results]: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide., [Conclusion]: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits., Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc.

Background A lack of objective data exists on differences in treatment practices and outcomes for MM between countries. The EMMOS study aimed to document and describe current treatment regimens and disease progression patterns of MM pts at different stages of the disease in real-world medical practice. Methods Adult pts initiating any new MM therapy, irrespective of treatment line at study entry or therapy type received, were eligible for inclusion in the EMMOS registry. A multi-staged pt/site recruitment model was applied to minimize selection bias; enrollment was stratified by country, region, and practice type. Pts' medical/disease features, treatment history, and remission status were recorded at baseline. Prospective data on treatment, efficacy, and safety were collected electronically every 3 mos until 2 yrs after the last pt enrolled. Responses were investigator-assessed (no predefined criteria). Here we report data from the final analysis of EMMOS. Pts were grouped according to receipt of high-dose chemotherapy/stem cell transplantation in any treatment line (SCT pts, non-SCT pts). Within a given line, pts may have received induction, SCT, consolidation, and/or maintenance therapy; if multiple drug combinations were used within a line, the line grouping was based on the combination received in cycle 1. Results 2358 pts were enrolled between Oct 2010-Oct 2012 in 22 countries in Europe and Africa; the last pt completed follow-up in Oct 2014. Of these, 775 pts had undergone SCT in any treatment line. Baseline characteristics in the prospective phase by starting line are shown in the Table. As expected, there was a higher proportion of younger pts (≤65 yrs) in the SCT vs non-SCT group across all treatment lines, and in both groups a higher proportion of pts in 4th + vs earlier lines with ISS stage III disease. While cytogenetics were evaluated in a small number of pts overall (670/2358 [28%]), these assessments were performed significantly more frequently in SCT vs non-SCT pts (p Conclusion This large, real-world, observational study provides for the first time a comprehensive picture of the baseline characteristics and therapy of MM pts treated in Europe, the Middle-East, and Africa. These data provide a framework towards the design of future protocols aiming to improve outcomes in MM. Table. Baseline characteristics by starting line Non-SCT pts SCT pts L1 (n=897) L2 (n=319) L3 (n=184) L4+ (n=166) Total* (N=1566) L1 (n=378) L2 (n=161) L3 (n=107) L4+ (n=120) Total* (N=775) Age ≤65 yrs, % 36 34 35 39 36 87 76 72 71 80 ISS Stage II/III, % 36/44 34/47 43/38 22/52 35/44 33/35 44/27 34/26 23/48 34/34 Salmon-Durie Stage 2/3, % 28/64 25/66 24/71 29/62 27/65 22/68 25/67 20/65 11/81 20/69 Bone lesion history, % 64 72 75 70 68 66 74 77 80 71 Cytogenetics assessed, % 24 19 19 14 21 51 35 43 33 44 Del 17p 8 8 9 13 8 10 7 4 13 9 t(4,14) 6 7 9 4 6 7 14 13 8 9 ISS, International staging system; L, line *17 non-SCT and 9 SCT pts were enrolled but did not receive a line of therapy within 75 days of baseline Disclosures Mohty: Celgene: Honoraria; Janssen: Honoraria. Terpos:Amgen: Honoraria, Research Funding; Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria. Mateos:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees. Palumbo:Array BioPharma: Consultancy; Onyx Pharmaceuticals: Consultancy; Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Genmab A/S: Consultancy; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy; Sanofi Aventis: Consultancy. Lejniece:Amgen: Honoraria; Sandoz: Honoraria. Beksac:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Dimopoulos:Novartis: Honoraria; Janssen: Honoraria; Amgen: Honoraria; Onyx: Honoraria; Celgene: Honoraria; Genesis Pharma: Research Funding. De Stefano:Shire: Speakers Bureau; Roche: Research Funding; Bruno Farmaceutici: Research Funding; Janssen Cilag: Research Funding; Amgen: Speakers Bureau; GlaxoSmithKline: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Celgene: Speakers Bureau. Salwender:Celgene: Honoraria; Janssen Cilag: Honoraria; Bristol Meyer Sqibb: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Pečeliūnas:Johnson & Johnson: Honoraria, Research Funding. Willenbacher:CTI: Consultancy, Other: Travel, Accommodations, Expenses; Gilead: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Amgen: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Janssen: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Roche: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding; Celgene: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding; Novartis: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Research Funding. Da Silva:Janssen Pharmaceuticals: Research Funding. Louw:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Nemet:Sanofi: Honoraria; Pliva: Honoraria; Pfizer: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Potamianou:Janssen: Employment. Couturier:Janssen-Cilag: Employment. Olie:Johnson & Johnson: Equity Ownership; Janssen-Cilag: Employment. Feys:Janssen Pharmaceutica N.V.: Employment, Equity Ownership. Thoret-Bauchet:Janssen-Cilag: Employment.

Many attempts have been made recently to improve the prognostic systems for non-Hodgkin’s lymphoma (NHL). There are no available data in the literature regarding the influence of intactness of the basement membrane of the blood vessels on the prognosis of NHL, when compared with the clinical characteristics of the disease. On the other hand, it is known that the integrity of the basement membrane is marker for the aggressiveness of the malignant disorders. In order to analyze the association of the expression patterns of collagen type IV on the prognosis of the patients with NHL we have conducted a retrospective study. We have evaluated 136 patients diagnosed and treated as NHL in the last ten years at the Clinic of Hematology, Medical Faculty -Skopje. All 136 patients with representative tumor tissues were diagnosed with NHL according to the REAL classification (71 patients were diagnosed as diffuse large cell lymphoma, 28 as follicular lymphoma, 24 as small lymphocytic lymphoma and 14 as marginal zone lymphoma). Median age of the patients was 49 years, with male: female ratio 1.5:1.0. The application of international prognostic index (IPI) identified four risk groups with predicted five-years survival rates of 87%, 82%, 18% and 0%, with statistical significance (p< 0.001). Using immunoperoxidase staining we have analyzed the collagen type IV expressing patterns in our group of patients, and defined three tumor invasive grades: high tumor invasive grade as total lack of immunoreactivity for collagen type IV (68 patients), medium-presented as discontinuous expression (56 patients) and low-as a continuous linear expression (14 patients). The 5 year overall survival rate was significantly lower (p Our results indicated that the expression of a collagen type IV immunoreactivity could predict the outcome of patients with NHL. However, further studies are needed to define the role of collagen type IV in the future prognostic systems for NHL.