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We describe a case of second primary malignancy in a 65-year-old patient affected by polycythemia vera treated with the JAK 1/2 inhibitor ruxolitinib. The latter is recognized as a risk factor for the onset of non-melanoma skin cancers in many retrospective and perspective studies, but the concomitant use of ruxolitinib with new immunotherapies is very rarely reported, and the safety of this association is still not clear. In our case, ruxolitinib combined with the anti-PD-L1 avelumab demonstrated both safety and efficacy for hematological disease control and underlying carcinoma remission. [ABSTRACT FROM AUTHOR]

Chronic myeloproliferative neoplasms (CMNs) are related to clonal over-proliferation of hematopoietic stem cells. Polycythemia vera, essential thrombocythemia and primary myelofibrosis are included in CMNs. An important complication of these diseases is thrombotic events. The relationship between Janus Kinase gene mutation and thrombosis in CMNs is still debated. Herein, we have aimed to investigate the impact of JAK2 mutation on thrombosis in philadelphia negative (Ph-) CMNs. The present study included 208 patients with Ph-CMNs who applied to the hematology clinic of Diskapi Yildirim Beyazit Training and Research Hospital for treatment and followed-up between 2013-2019. The patient data were retrospectively reviewed. Statistical analysis was performed with SPSS V.25.0. The statistical significance level was accepted as p< 0.05.Multivariate analysis was performed to the variables with p< 0.01 in the univariate analysis. When comparing the thrombosis and non-thrombosis groups in univariate logistic regression analysis, there was a borderline statistically significant difference in gender (p= 0.058) and statistically significant differences were found in the presence of diabetes mellitus (p= 0.001), hypertension (p< 0.001), hyperlipidemia (p= 0.025) and serum calcium (p= 0.028). According to multivariate logistic regression analysis, gender (p= 0.032), diabetes mellitus (p= 0.027), and serum calcium (p= 0.031) were found to be associated with thrombosis. When these three parameters were examined together, 94.2% sensitivity and 43.8% specificity were detected. The overall predictive accuracy for thrombosis was found to be 84.2%.Also there was statistically significant difference in sedimentation, C-reactive protein, AST levels and size of liver between the thrombotic and non-thrombotic patients in univariate analysis. There was no statistically significant relationship between the presence of JAK2 mutation (p= 0.637) and JAK2 allele burden (p= 0.885) with thrombosis. Cardiovascular risk factors were found to be related with thrombosis in Ph-CMNs rather than presence of JAK2 mutation or JAK2 allele burden. [ABSTRACT FROM AUTHOR]

We describe a case of second primary malignancy in a 65-year-old patient affected by polycythemia vera treated with the JAK 1/2 inhibitor ruxolitinib. The latter is recognized as a risk factor for the onset of non-melanoma skin cancers in many retrospective and perspective studies, but the concomitant use of ruxolitinib with new immunotherapies is very rarely reported, and the safety of this association is still not clear. In our case, ruxolitinib combined with the anti-PD-L1 avelumab demonstrated both safety and efficacy for hematological disease control and underlying carcinoma remission.

Myeloproliferative neoplasms are hematological disorders characterized by increased production in one or more myeloid cell lines, associated with driver mutations in JAK2-, MPL- and CALR-genes. The aims of this study were to investigate the prevalence of these driver mutations in a Norwegian patient cohort with myeloproliferative neoplasms, and to assess whether the different mutations were associated with different clinical presentation and natural history. Results from 820 patients in whom analysis for JAK2V617F-, CALR- and MPL had been performed at Haukeland University Hospital in the period 2014-2019 were retrieved and analyzed together with clinical variables related to diagnosis, hematological blood parameters and complications, obtained from patient records. We identified 182 cases of myeloproliferative neoplasms: 78 with JAK2V617F, 28 with CALR-mutations, two with MPL-mutations and 23 cases without a driver mutation. There was a lower prevalence of JAK2V617F mutation than expected in the polycythemia vera group, likely related to overdiagnosis. In patients with essential thrombocytosis, we found significantly higher levels of hemoglobin and erythrocyte volume fraction for JAK2V617F-mutated disease, and significantly higher levels of platelets and lactate dehydrogenase for CALR-mutated disease. Patients with JAK2V617F-mutated primary myelofibrosis had significantly higher levels of hemoglobin, and there was an increased number of smokers or former smokers in this group compared to patients with CALR-mutations. Except for a lower prevalence of JAK2V617F-mutation in polycythemia vera, the mutational distribution in our patient cohort was similar to previous findings in other populations. The novel finding of a higher prevalence of smokers in JAK2V617F-mutated primary myelofibrosis warrants further investigation. [ABSTRACT FROM AUTHOR]

Introduction: Interferon alfa (IFN-α) has been used for over 30 years to treat myeloproliferative neoplasms. Recombinant IFN-α (rIFN-α) and pegylated IFN-α (Peg-IFN-α) have been shown to provide effective therapy for essential thrombocythemia (ET) and polycythaemia vera (PV), as well as early stage primary myelofibrosis (PMF) in several clinical studies. Patients and methods: This report presents a retrospective analysis of 60 patients with MPN who were treated with rIFN-α or Peg-IFN-D outside clinical trials. Results: Retrospective stratification at diagnosis included 34 (57%) patients with PV, 5 (8%) with ET and 21 (35%) with PMF. Median age was 43 years (16-70). Median treatment duration was 107.5 months, with 11 patients treated with Peg IFN-D for a median duration of 24 months. Median follow up was 164 months. 24 patients (40%) achieved complete remission, 29 patients (48%) achieved partial remission and 7 patients (12%) failed to achieve partial remission. Toxicities were recorded in 42 patients (70%): chronic „flu-like syndrome", psychiatric toxicity, hepatotoxicity, dermatotoxicity, ocular and neurotoxicity. Thirteen (22%) patients stopped the treatment because of toxicity. Conclusion: IFN-α effectively controls disease in a significant proportion of Ph-negative MPN patients. However, its use in clinical practice has unfortunately been limited by side effects. These results support the need for further efficacy studies of IFN-α in this group of patients. [ABSTRACT FROM AUTHOR]

A 55-year-old male with a history of positive HIV serology and Polycytemia vera underwent coronary artery bypass graft surgery with normothermic extracorporeal circulation. Following heparin administration the activated clotting time (ACT) was 633 seconds (Hemocron® with kaolin). Lower than expected arterial and venous oxygen partial pressures together with high pressure (350 mmHg) in the arterial line upstream of the oxygenator were observed. Because of these signs the oxygenator was changed during the procedure. The outcome was uneventful. Electronic microscopic examination of the oxygenator membrane and thermic exchanger revealed fibrin and platelet deposits. [Copyright &y& Elsevier]

In the diagnosis of polycytemia vera, estimation of erythrocyte volume (EV) from plasma volume (PV) and venous hematocrit (Hct) is usually thought unadvisable, because the ratio of whole body hematocrit to venous hematocrit ( f ratio) is higher in patients with splenomegaly than in normal subjects, and varies considerably between individuals. We determined the mean f ratio in 232 consecutive patients suspected of polycytemia vera ( $$\bar f = {\text{0}}{\text{.967}}$$ ;SD 0.048) and used it with each patient's PV and Hct to calculate an estimated normalised EV. With measured EV as a reference value, EV was investigated as a diagnostic test. By means of two cut off levels the EV values could be divided into EV elevated, EV not elevated (both with high predictive values), and an EV borderline group. The size of the borderline EV group ranged from 5% to 46% depending on position of the cut off levels, i.e. with the efficiency demanded from the diagnostic test. EV can safely and rapidly be estimated from PV and Hct, if $$\bar f$$ is determined from the relevant population, and if the results in an easily defineable borderline range of EV values are supplemented by direct EV determination. [ABSTRACT FROM AUTHOR]

Abstract: Neurological manifestations in polycytemia vera are common. However, chorea is an exceptionally revealing feature of this disease. We report a 78-year-old man who presented with headache and an abnormal movement disorder corresponding to chorea. Laboratory findings showed increased levels of hemoglobin at 20g/dl and hematocrit at 62.3%. An elevated erythrocyte mass to twice the normal value demonstrated the absolute erythrocytosis. A JAK2 V617F gene mutation was identified. A diagnosis of polycytemia vera-associated chorea was obtained. Clinical and biological outcomes were favorable after therapeutic phlebotomy and treatment with hydroxyurea. We recommend a complete blood cell count in elderly patient presenting with chorea to eliminate a diagnosis of polycytemia vera. [Copyright &y& Elsevier]