No abstract

BackgroundPrior thrombosis is a well-established risk factor for re-thrombosis in polycythemia vera and essential thrombocythemia but scarce data are available on the rate of re-thrombosis and the optimal strategy for prevention of recurrence.

The optimal duration of treatment with vitamin K antagonists (VKA) after venous thromboembolism (VTE) in patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) is uncertain. To tackle this issue, we retrospectively studied 206 patients with MPN-related VTE (deep venous thrombosis of the legs and/or pulmonary embolism). After this index event, we recorded over 695 pt-years 45 recurrences, venous in 36 cases, with an incidence rate (IR) of 6.5 per 100 pt-years (95% confidence interval (CI): 4.9-8.6). One hundred fifty-five patients received VKA; the IR of recurrent thrombosis per 100 pt-years was 4.7 (95% CI: 2.8-7.3) on VKA and 8.9 (95% CI: 5.7-13.2) off VKA (P=0.03). In patients receiving VKA, the IR of recurrent thrombosis per 100 pt-years was 5.3 (95% CI: 3.2-8.4) among 108 patients on long-term VKA and 12.8 (95% CI: 7.3-20.7) after discontinuation among the 47 who ceased treatment (P=0.008), with a doubled risk of recurrence after stopping VKA (hazard ratio: 2.21, 95% CI: 1.19-5.30). The IR of major bleeding per 100 pt-years was 2.4 (95%: CI: 1.1-4.5) on VKA and 0.7 (95% CI: 0.08-2.5) off VKA (P=0.08). In conclusion, in MPN patients with VTE recurrent thrombosis is significantly reduced by VKA and caution should be adopted in discontinuation; however, the incidence of recurrence on treatment remains high, calling for clinical trials aimed to improve prophylaxis in this setting.

below the mean BMD in young adults (20-40 years old) of the same gender. The Z-score denotes how many SDs a person's BMD is above or below the mean BMD in the matched population. The coefficient of variation (CV) for the areal BMD measurements ranged from 0.5 to 3%, depending on application.Peripheral quantitative computerized tomography. The volumetric BMD (g/cm 3 ) of the nondominant distal arm (the radial bone) and distal leg (the tibial bone) was measured by pQCT (XCT-2000, Stratec Medizintechnik, GmbH, Pforzheim, Germany). The pQCT-device was calibrated once a week using a standard phantom and once every 30 day using a cone phantom provided by the manufacturer. A 2-mm-thick single tomographic slice was scanned with a voxel size of 0.50 mm. The cortical volumetric BMD was measured using a scan through the diaphysis at 25% of the bone length in the proximal direction of the distal end of the radial and tibial bones, respectively. Trabecular volumetric BMD was measured using a scan through the metaphysis at 4% of the bone length in the proximal direction of the distal end of the radial and tibial bones, respectively. All pQCT analyses were performed by a single technician using a single pQCT device. The CVs were less than 1% for all pQCT measurements, as previously reported [25].Statistics. Paired two-sided t-tests and Wilcoxon signed rank tests were performed to evaluate differences over time in each group. Unpaired twosided t-tests and Mann-Whitney U were performed to compare CML patients and controls. Fischer's exact test was used to compare the number of individuals with hyperparathyroidism in 2007 and 2011, respectively. A P < 0.05 was considered statistically significant. All data shown are mean values ± standard error of mean (SEM) unless otherwise stated.

We conducted a large international nested case-control study including 1,881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n=647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer and melanoma) and controls (n=1,234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR=1.06, 95% CI 0.82-1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had twofold higher risk of non-melanoma (NM) skin cancer (OR=2.28, 95% CI 1.15-4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR=3.74, 95% CI 1.00-14.01), ruxolitinib (OR=3.87, 95% CI 1.18-12.75) and for drug combination (OR=3.47, 95% CI 1.55-7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.