Search

Background: Therapeutic phlebotomy (TP) is a well-established medical intervention that evolved from the historical practice of bloodletting., Methods: Patients who require TP are not infrequently told by their health-care providers to "just go donate blood," but TP should always be offered in the context of a prescribed course of therapy. Providers can prescribe a course of TP for a number of indications, including hereditary hemochromatosis, polycythemia vera, iron overload, and testosterone replacement therapy., Results: A course of prescribed TP specifies that patients can be phlebotomized more frequently than volunteer blood donors and reassures patients that TP is being performed per the orders of their provider. Prescribed TP also facilitates two-way communication between the referring provider and the transfusion medicine (TM) physician overseeing the TP. The College of American Pathologists TM checklist describes several requirements regarding the documentation and performance of TP, and electronic medical record systems can be used to demonstrate compliance with these requirements., Conclusions: TM physicians should discuss the advantages of prescribing TP with providers who mutually care for patients requiring this intervention., (© 2021 AABB.)

Background/aim: Polycythemia rubra vera (PRV) is a myeloproliferative disease, which is characterized by the proliferation of all three major hematopoietic groups (erythrocytes, leucocytes and platelets). This hematological condition presented with different clinical manifestations depending on the thrombohemorrhagic status of the patient. It is suggested patient with preexisting PRV may suffer complication during periodontal treatment. Thus, this case would therefore demonstrate periodontal management outcome in PRV patient., Case Presentation: A 60-year-old Malay gentleman presented to the Periodontic Clinic, Universiti Kebangsaan Malaysia. He was a known case of primary PRV for the past 5 years. Intraoral examination showed generalized periodontal deep pockets ranging from 5 to 10 mm. He was diagnosed as Stage III Grade C periodontitis. Nonsurgical periodontal therapy was provided, followed by surgical correction of residual periodontal deep pockets on teeth 17, 11, and 23. He was reviewed at 4-month intervals for supportive periodontal therapy after stabilization of his periodontal condition., Conclusion: Polycythemia rubra vera (PRV) patients should have preoperative therapeutic control for more than 4 months and have been treated with myelosuppressive agents prior to periodontal surgery. Good oral hygiene and periodical supportive periodontal therapy are the key factors for successful periodontal treatment outcomes in well-controlled PRV patients., (© 2020 Special Care Dentistry Association and Wiley Periodicals LLC.)

Essential thrombocythemia (ET) and polycythemia vera (PV) are myeloproliferative neoplasms (MPN), wherein JAK2 V617F mutation exists as a common driver mutation, and the JAK-STAT pathway is constitutively activated. The treatment goal for ET and PV is the prevention of thrombosis and bleeding. The treatment strategy for ET is careful observation or antiplatelet therapy with or without cytoreductive therapy based on the thrombotic risk. The treatment strategy for all PV patients is phlebotomy with a target hematocrit of <45% in addition to antiplatelet therapy. Moreover, for patients at a high risk of thrombosis, additional cytoreductive therapy is considered beneficial. In this session, we discuss important points for ET diagnosis, thrombotic risk stratification, and the details of treatment strategy and current practice with evidence from clinical trials in ET. Furthermore, current topics in the treatment of ET and PV will be introduced with a focus on clinical data about interferon-α, which is reported to induce not only hematologic response but also molecular and histopathologic response in MPN.

Hyperactive signaling of the Janus-Associated Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) pathway is central to the pathogenesis of Philadelphia-chromosome-negative myeloproliferative neoplasms (MPN), i.e., polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) which are characterized by inherent biological and clinical heterogeneity. Patients with MPNs suffer from substantial symptom burden and curtailed longevity due to thrombohemorrhagic complications or progression to myelofibrosis or acute myeloid leukemia. Therefore, the management strategies focus on thrombosis risk mitigation in PV/ET, alleviation of symptom burden and improvement in cytopenias and red blood cell transfusion requirements, and disease course alteration in PMF. The United States Food and Drug Administration's (USFDA) approval of two JAK inhibitors (ruxolitinib, fedratinib) has transformed the therapeutic landscape of MPNs in assuaging the need for frequent therapeutic phlebotomy (PV) and reduction in spleen and symptom burden (PV and PMF). Despite improving biological understanding of these complex clonal hematopoietic stem/progenitor cell neoplasms, none of the currently available therapies appear to modify the proclivity of the disease per se, thereby remaining an urgent unmet clinical need and an ongoing area of intense clinical investigation. This review will highlight the evolving targeted therapeutic agents that are in early- and late-stage MPN clinical development.

Competing Interests: Conflict of interest The authors declare no conflict of interest.

Polycythemia vera (PV) is mainly characterized by elevated blood cell counts, thrombotic as well as hemorrhagic predisposition, a variety of symptoms, and cumulative risks of fibrotic progression and/or leukemic evolution over time. Major changes to its diagnostic criteria were made in the 2016 revision of the World Health Organization (WHO) classification, with both hemoglobin and hematocrit diagnostic thresholds lowered to 16.5 g/dL and 49% for men, and 16 g/dL and 48% for women, respectively. The main reason leading to these changes was represented by the recognition of a new entity, namely the so-called "masked PV", as individuals suffering from this condition have a worse outcome, possibly owing to missed or delayed diagnoses and lower intensity of treatment. Thrombotic risk stratification is of crucial importance to evaluate patients' prognosis at diagnosis. Currently, patients are stratified into a low-risk group, in the case of younger age (<60 years) and no previous thromboses, and a high-risk group, in the case of patients older than 60 years and/or with a previous thrombotic complication. Furthermore, even though they have not yet been formally included in a scoring system, generic cardiovascular risk factors, particularly hypertension, smoking, and leukocytosis, contribute to the thrombotic overall risk. In the absence of agents proven to modify its natural history and prevent progression, PV management has primarily been focused on minimizing the thrombotic risk, representing the main cause of morbidity and mortality. When cytoreduction is necessary, conventional therapies include hydroxyurea as a first-line treatment and ruxolitinib and interferon in resistant/intolerant cases. Each therapy, however, is burdened by specific drawbacks, underlying the need for improved strategies. Currently, the therapeutic landscape for PV is still expanding, and includes several molecules that are under investigation, like long-acting pegylated interferon alpha-2b, histone deacetylase inhibitors, and murine double minute 2 (MDM2) inhibitors.

Purpose: A new software release of the Fenwal Amicus device is now available for red blood cell (RBC) apheresis, offering RBC exchange, RBC depletion (RBCd)/RCB exchange, and RBCd procedures. The main goal of this study was to validate the new RBCd program through the accuracy of the patient's postprocedure hematocrit (HCT) (actual end HCT) to the HCT reported by the device at the end of the procedure (target end HCT). Secondary objectives were to assess the device-related significant adverse events, the patient's cellular losses, and the degree of device induced hemolysis., Methods: The study was an open-label, single-center, prospective trial in adult patients eligible for RBCd. Patients were enrolled between October 2015 and June 2016. In all procedures, saline was used as replacement fluid. Blood samples were collected from the patient before and after the procedure. Device settings, adverse events, and procedure results were recorded., Results: Thirty-nine patients were enrolled (34 treated for iron storage disease and 5 for polycythemia vera); only 36 were evaluable for the primary objective. The mean actual end HCT was 34.6 ± 2.79% and the mean target end HCT was 35.8 ± 2.25%. The ratio (actual end to target end HCT) was 0.97 ± 0.05 with a 95% CI demonstrating the accuracy of the target HCT. One patient experienced a vasovagal event not related to the device. Cellular losses were not clinically relevant., Conclusion: The RBCd Amicus program met all RBCd efficiency and safety requirements with high accuracy of the target HCT., (© 2020 Wiley Periodicals, Inc.)

Health resource utilization (HRU) and associated factors of high cost are not well understood in myeloproliferative neoplasms (MPNs). In this population-based, retrospective matched-cohort study, we used administrative health databases of Ontario, Canada to measure treatment costs and HRU for patients with MPN from 2004 to 2016 and compared them to matched controls. In 7130 patients with MPN [essential thrombocythemia (ET) = 3481; polycythemia vera (PV) = 2618; myelofibrosis (MF) = 1031], the mean annualized treatment costs were $16,646 for ET (controls, $7070); $16,360 for PV (controls, $7293); and $25,863 for MF (controls, $7386). Out of the total costs, the largest expenditure was on acute hospital care (ET: 57%, PV: 57%, MF: 66%). Older age (≥65), male gender, patients not seen by a specialist, and greater comorbidity burden were independent predictors of higher costs ( p  < 0.05). In addition, history of venous thrombosis in patients with ET and PV was associated with significantly higher treatment costs ( p  < 0.05).

In this retrospective, real-world study, we used medical claims data to evaluate the incidence of thromboembolic events (TEs), time to TE, associated risk factors, and health-care resource utilization (HRU) in Japanese patients with polycythemia vera (PV; N = 606) from April 1, 2008, to August 31, 2015. Baseline characteristics of interest included median age, 67.0 years; previous TEs, 11.6%; cardiovascular conditions (CVCs), 45.7%; and ≥ 3 risk factors, 17.8%. Overall, 100 patients experienced TEs (118 events) at a rate of 8.15/100 person-years [TE-free survival rate, 69.3% (2008-2015)]. The annual total health-care costs [mean (per person)] were significantly impacted by the presence of TEs (yes vs. no: ¥993,000 vs ¥459,000; P < 0.001). These results confirm that the presence of CVCs increases the risk of TEs in Japanese patients with PV; occurrence of TEs was associated with a higher HRU in these patients.

Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms characterized by increased rate of cardiovascular events, a varying burden of symptoms, and an intrinsic risk of evolution to secondary forms of myelofibrosis and acute leukemia; however, survival is only modestly reduced in most instances. In the last few years, following the description of driver mutations in JAK2, MPL and CALR, the diagnostic criteria for PV and ET were revised, making the identification of very early stages feasible. Scores for identifying patients at different risk of thrombosis were refined, and they largely guide therapeutic decisions. Treatment is therefore mainly focused on reduction of thrombosis risk, control of myeloproliferation, improvement of symptomatic burden, and management of disease-associated complications. New drugs recently entered the clinical arena, with the promise to improve overall patients' management. However, evidence of a disease-modifying potential is largely missing and represents a still unmet clinical need., Competing Interests: Declaration of Competing Interest AMV received personal fees for advisory board from Novartis, Celgene, CTI, Incyte. PG received personal fees for advisory board from Novartis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: Polycythemia vera is a myeloproliferative neoplasm (MPN) characterized by increased red blood cell mass. The natural evolution of this MPN is to progress to an anemic/cytopenic phase also known as "spent" phase prior to transformation into an accelerated and/or an overt leukemic phase., Case Report: Herein, we describe a case of a patient with polycythemia vera transitioning though a "spent" phase to an MPN in accelerated phase (MPN-AP). The patient had anemia, thrombocytopenia, neutrophilia and increased blasts in the bone marrow. Management and outcome: Upon treatment with four cycles of 5-azacitidine, the patient's polycythemia vera reversed back to the proliferative phase. Serial phlebotomies were again required., Discussion: Reversal of a "spent" phase by 5-azacitidine back to a proliferative polycythemia vera phase requiring phlebotomies has not been previously reported in the scientific literature. We might witness similar cases in the literature in the future years, which could lead to yet another therapeutic indication of this important pharmacologic agent.

Therapeutic erythrocytapheresis (TE) is a more efficient strategy compared to phlebotomy to deplete levels of haematocrit in primary and secondary erythrocytosis., Objective: To analyse response rate and safety profile of TE in polycythemia vera (PV) and secondary erythrocytosis (SE)., Patients and Method: Retrospective review of all patients with PV or SE treated with TE, due to phlebotomy failure, or comorbidities that prevented changes of blood volumen., Results: 217 TE sessions (48 PV and 79 SE) corresponding to 20 patients (12 ES and 8 PV). Response were achieved in 87.5% of PV patients and in 50% of SE patients. Adverse effects related to TE performance occurred in 7.08%., Conclusion: Despite our small sample size and the heterogeneous nature of the patients included, we can postulate that TE is a secure strategy that can achieve haematocrit depletion in a shorter time than phlebotomy, specifically in PV patients and in selected cases of SE with expected haemodynamic intolerance to phlebotomies or in patients who fail to respond to phlebotomies., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)

Objectives: Assessment of "real-world" treatment strategies and outcome in Dutch polycythemia vera (PV) patients., Methods: Retrospective chart review in 150 patients with PV (WHO 2008 diagnostic criteria) from 10 major non-academic hospitals in the Netherlands., Results: Patients (median age 64 years, 49% male) frequently had cardiovascular risk factors (56%) and prior vascular events (31%). About 70% of patients were high-risk, based on ELN criteria. However, the majority of patients were treated with phlebotomies alone (55%). Cytoreduction with hydroxyurea (HU) was received by 44% as part of their initial therapy, with or without phlebotomies. The time to achieve the 45% hematocrit target was shortest in patients treated with phlebotomies with or without HU (125 ± 99 and 197 ± 249 days, respectively) compared to patients treated with only HU (232 ± 216 days). Leukocyte and platelet levels were lower in HU-treated patients, and ELN response targets were more often reached. During the median follow-up period of 4.1 years, 14 patients (9%) suffered a thrombotic vascular event., Conclusions: In Dutch clinical practice, there is major clinical variation in treatment strategies for PV. Phlebotomizing patients shorten the time to achieve hematocrit control, while HU better controls platelet and leukocyte levels. The thrombotic vascular event rate remains clinically significant., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Polycythaemia Vera (PV) is a myeloproliferative disorder in which bone marrow has increased production of red blood cells, white blood cells and platelets. The hallmarks of the disease are veno-occlusive events, secondary to increased blood viscosity. Polycythaemia Vera rarely presents with portal vein thrombosis below age of 55 years especially in absence of any chronic liver disease. We report a case of 30-years-old South Asian male presenting with abdominal pain, weight loss and vomiting for 3 months. On evaluation, he was found to have oesophageal varices. Furthermore, CT scan showed infiltration at porta-hepatis and portal venous thrombosis. Polycythaemia Vera was diagnosed with a positive JAK2 mutation and increased haemoglobin. Laparoscopy was done to perform biopsy of the porta-hepatis mass. Biopsy showed engorged vessels with no sign of malignancy. Patient underwent repeated sessions of upper GI endoscopy for band ligation and multiple sessions of venous phlebotomy which drastically improved his blood indices. He was started on lifelong aspirin and was advised regular follow-ups. With early recognition and prompt management patients can be prevented from potential complications which can prove to be detrimental.

Background: Approximately 50% of patients with polycythemia vera (PV) have PV-related symptoms at diagnosis; these symptoms might develop or worsen with time. Symptoms have been shown to negatively affect quality of life and interfere with daily activities. To our knowledge, an analysis to evaluate the relationship between blood count control and symptoms has not been published., Patients and Methods: The Prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices (REVEAL; NCT02252159) is a multicenter, noninterventional, nonrandomized prospective observational study of patients with PV in the United States. Patients included were required to have a complete blood count result within 30 days before completing the at-enrollment Myeloproliferative Neoplasm Self-Assessment Form Total Symptom Score (MPN-SAF TSS). Symptom severity was compared between those who had blood count control versus those who did not., Results: At the time of enrollment, 1714 patients (94.5%) were being managed with cytoreductive therapy; 468 patients (25.8%) had complete hematologic remission (CHR), 1614 patients (89.0%) had ≥1 controlled blood count, and 1122 patients (61.9%) had ≥2 controlled blood counts. Mean MPN-SAF TSSs were similar across patients in different blood count control groups. Fatigue was the most frequently reported symptom. The severity of individual symptoms, except those of pruritus and night sweats, was not affected by CHR or the number of blood counts that were controlled., Conclusion: Symptom burden in patients with PV can persist despite control of blood counts, which suggests some discordance between laboratory values and symptom burden. Consequently, regular monitoring of symptom burden should be factored into the assessment of disease control., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

CME: Polycythemia vera Abstract. Polycythemia vera is a myeloprolifere disease which is characterized by proliferation of all three (erythroid, megakaryocytic and granulocytic) cell lines. The causative mutation is in the JAK2-tyrosine kinase gene. The symptoms are related to the increased red blood cells. Common signs are itching (pruritus) and pain in the hands or feet. The most common complications are thrombotic events. Risk factors are age over 60 years and a thrombotic event in the patient's history. The treatment consists of phlebotomy combined with acetylsalicylic acid 100 mg a day. The goal of the therapy is the prevention of the common thrombotic events. During the course of the disease, cytoreductive treatment is indicated in most of the patients.

Polycythemia vera is a chronic myeloproliferative neoplasm, which is primarily characterized by elevated erythrocyte count with the risk of thrombosis, hemorrhage, and vasomotor symptoms. More common reported about bleeding events are gastrointestinal, mucosal, and cutaneous bleeding. Spontaneous cerebral hemorrhage/bleeding is seldom reported. Here, we report the case of a 50-year-old female with polycythemia vera who developed a spontaneous cerebral hemorrhage. She improved significantly after hydroxyurea agent and red cell apheresis, and the hematocrit decreased from 74% to 40%., (Copyright © 2019. Published by Elsevier Inc.)

We report the case of a 59 year old woman who presented with a six week history of worsening bifrontal headache. On CT brain the only abnormal finding was a partially empty sella potentially indicative of increased intracranial pressure. MRI found a large cerebral venous sinus thrombosis in the superior sagittal sinus. Blood tests and a bone marrow biopsy revealed a diagnosis of JAK2 positive primary polycythaemia rubra vera. The lack of sensitivity and specificity of CT in the diagnosis of CVST should engender a low threshold for MRI in patients with risk factors and/or non-diagnostic abnormalities on initial CT. Management of this dual pathology involves both the immediate treatment of the thrombus with heparin bridging to warfarin and the long treatment for polycythaemia involving repeat venesections and cytoreductive therapy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Since its discovery, polycythemia vera (PV) has challenged clinicians responsible for its diagnosis and management and scientists investigating its pathogenesis. As a clonal hematopoietic stem cell (HSC) disorder, PV is a neoplasm but its driver mutations result in overproduction of morphologically and functionally normal blood cells. PV arises in an HSC but it can present initially as isolated erythrocytosis, leukocytosis, thrombocytosis, or any combination of these together with splenomegaly or myelofibrosis, and it can take years for a true panmyelopathy to appear. PV shares the same JAK2 mutation as essential thrombocytosis and primary myelofibrosis, but erythrocytosis only occurs in PV. However, unlike secondary causes of erythrocytosis, in PV, the plasma volume is frequently expanded, masking the erythrocytosis and making diagnosis difficult if this essential fact is ignored. PV is not a monolithic disorder: female patients deregulate fewer genes and clinically behave differently than their male counterparts, while some PV patients are genetically predisposed to an aggressive clinical course. Nevertheless, based on what we have learned over the past century, most PV patients can lead long and productive lives. In this review, using clinical examples, I describe how I diagnose and manage PV in an evidence-based manner without relying on chemotherapy., (© 2019 by The American Society of Hematology.)

In the last years, a growing amount of evidence has been produced regarding the role of leukocytosis as a risk factor for thrombosis in patients with myeloproliferative neoplasms, predominantly in polycythemia vera (PV) and essential thrombocythemia (ET). Results from epidemiologic studies on this issue, however, are inconclusive. We conducted a systematic review and meta-analysis of articles published in the last 12 years addressing the issue, according to a predefined protocol. Forty-one articles analyzing >30 000 patients met our inclusion criteria and were deemed of acceptable methodologic quality. In addition to data on thrombosis, data were collected on bleeding, hematologic evolution, secondary cancer, and death. The relative risk (RR) of thrombosis in the presence of leukocytosis was 1.59 (95% CI, 1.40-1.80), mainly accounted for by ET (RR, 1.65; 95% CI, 1.43-1.91) and arterial thrombosis (RR, 1.45; 95% CI, 1.13-1.86) subgroups; the effect was not significant in venous thrombosis alone. Sensitivity analyses considering recurrent events as well as white blood cell estimates adjusted or unadjusted for confounding factors confirmed the primary results. In addition, the pooled RR of studies that tested white blood cell counts in time-dependent models suggested a causative effect of leukocytes in the mechanism that triggers thrombosis. The effect of leukocytosis on bleeding (RR, 1.87; 95% CI, 1.26-2.77) and death (RR, 1.89; 95% CI, 1.59-2.23) was confirmed, whereas conclusions on hematologic evolutions and solid tumors were uncertain. To confirm the accuracy of these results, an investigation on individual patient data in a large collective archive of homogeneous patients is warranted., (© 2019 by The American Society of Hematology.)

We aimed to validate the MYelofibrosis SECondary to PV and ET prognostic model (MYSEC-PM) in 159 patients with myelofibrosis secondary to polycythemia vera (PV) and essential thrombocythemia (ET) from the European Society for Blood and Marrow Transplantation registry undergoing transplantation from matched siblings or unrelated donors. Furthermore, we aimed to test its prognostic performance in comparison with the Dynamic International Prognostic Scoring System (DIPSS). Score performance was analyzed using the concordance index (C): the probability that a patient who experienced an event had a higher risk score than a patient who did not (C > .5 suggesting predictive ability). Median follow-up of the total cohort was 41 months (range, 34 to 54), 45 months in post-PV and 38 months in post-ET myelofibrosis. Survival at 1, 2, and 4 years was 70% (95% CI, 63% to 77%), 61% (95% CI, 53% to 69%), and 52% (95% CI, 43% to 61%) for the total cohort; 70% (95% CI, 59% to 80%), 61% (95% CI, 49% to 73%), and 51% (95% CI, 38% to 64%) for post-PV; and 71% (95% CI, 61% to 81%), 61% (95% CI, 50% to 72%), and 54% (95% CI, 42% to 66%) for post-ET myelofibrosis (P = .78). Overall, the DIPSS was not significantly predictive of outcome (P = .28). With respect to the MYSEC-PM, overall survival at 4 years was 69% for the low-risk, 55% for the intermediate 1-risk, 47% for the intermediate 2-risk, and 22% (0% to 45%) for the high-risk groups. The prognostic model was predictive of survival overall (P = .05), whereas groups with intermediate 2 and high risk showed no significant difference (P = .44). Assessment of prognostic utility yielded a C-index of .575 (95% CI, .502 to .648) for the DIPSS, whereas assessment of the MYSEC-PM resulted in a C-statistics of .636 (95% CI, .563 to .708), indicating improvement in prediction of post-transplant survival using the new MYSEC-PM. In addition, transplantations from an unrelated donor in comparison with an HLA-identical sibling showed worse outcome (P = .04), and transplant recipients seropositive for cytomegalovirus in comparison with seronegative recipients (P = .01) showed worse survival. In conclusion, incorporating transplant-specific and clinical and mutational information together with the MYSEC-PM may enhance risk stratification., (Copyright © 2019 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Thromboembolic events and cardiovascular disease are the most prevalent complications in patients with polycythemia vera (PV) compared with other myeloproliferative disorders and are the major cause of morbidity and mortality in this population. Moreover, a vascular complication such as arterial or venous thrombosis often leads to the diagnosis of PV. The highest rates of thrombosis typically occur shortly before or at diagnosis and decrease over time, probably due to the effects of treatment. Important risk factors include age (≥ 60 years old) and a history of thrombosis; elevated hematocrit and leukocytosis are also associated with an increased risk of thrombosis. The goal of therapy is to reduce the risk of thrombosis by controlling hematocrit to < 45%, a target associated with reduced rates of cardiovascular death and major thrombosis. Low-risk patients (< 60 years old with no history of thrombosis) are managed with phlebotomy and low-dose aspirin, whereas high-risk patients (≥ 60 years old and/or with a history of thrombosis) should be treated with cytoreductive agents. Interferon and ruxolitinib are considered second-line therapies for patients who are intolerant of or have an inadequate response to hydroxyurea, which is typically used as first-line therapy. In this review, we discuss factors associated with thrombosis and recent data on current treatments, including anticoagulation, highlighting the need for more controlled studies to determine the most effective cytoreductive therapies for reducing the risk of thrombosis in patients with PV.

Background: The 2016 World Health Organization (WHO) revised classification criteria for the diagnosis of polycythemia vera (PV) allows for an earlier detection of masked PV. The literature is scarce about the clinical uptake of new diagnostic algorithms for PV. In a cohort of Canadian hematologists, we aimed to identify how the revised 2016 WHO diagnostic criteria of PV are being incorporated into hematology practice, and if the treatment of PV is comparable to the approaches outlined by the Canadian Myeloproliferative Neoplasm Group., Materials and Methods: A cross-sectional survey of practicing Canadian hematologists/oncologists was distributed to active members of the Canadian Hematology Society using an online survey-distributing website. Univariate and multivariate analysis was performed., Results: The survey was completed by 86 respondents in total. Only type of practice was associated with respondents offering aspirin to all patients with PV (P = .0009). Respondents who were aware of the Canadian Myeloproliferative Neoplasm Group guidelines were more likely to phlebotomize patients to a target hematocrit of < 45% irrespective of gender (P = .042). Younger practitioners were more likely to use age over 60 years as an indication for initiating cytoreductive therapy (P = .0006). Most (85.3%) respondents would recommend indefinite anticoagulation in patients with PV who developed unprovoked venous thromboembolism., Conclusion: The survey confirmed that heterogeneity of practice in diagnosis and management of PV among Canadian hematologists exists, suggesting that targeted education in specific segments of the PV treatment providers may result in wider adoption of the guidelines and diagnostic criteria., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Disease Overview: Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms respectively characterized by erythrocytosis and thrombocytosis; other disease features include leukocytosis, splenomegaly, thrombosis, bleeding, microcirculatory symptoms, pruritus, and risk of leukemic or fibrotic transformation. Diagnosis: Bone marrow morphology remains the cornerstone of diagnosis. In addition, the presence of JAK2 mutation is expected in PV while approximately 90% of patients with ET express mutually exclusive JAK2, CALR, or myeloproliferative leukemia mutations. In ET, it is most important to exclude the possibility of prefibrotic myelofibrosis. Survival: Median survivals are 14 years for PV and 20 years for ET; the corresponding values for younger patients are 24 and 33 years. Certain mutations (mostly spliceosome) and abnormal karyotype might compromise survival in PV and ET. Life-expectancy in ET is inferior to the control population. Driver mutations have not been shown to affect survival in ET. Risk of thrombosis is higher in JAK2-mutated ET. Leukemic transformation rates at 10 years are estimated at <1% for ET and 3% for PV. Thrombosis Risk: In PV, 2 risk categories are considered: high (age > 60 years or thrombosis history present) and low (absence of both risk factors); in ET, 4 risk categories are considered: very low (age ≤ 60 years, no thrombosis history, JAK2 wild-type), low (same as very low but JAK2 mutation present), intermediate (age > 60 years, no thrombosis history, JAK2 wild-type) and high (thrombosis history present or age > 60 years with JAK2 mutation). Risk-Adapted Therapy: The main goal of therapy in both PV and ET is to prevent thrombohemorrhagic complications. All patients with PV require phlebotomy to keep hematocrit below 45% and once- or twice-daily aspirin (81 mg), in the absence of contraindications. Very low-risk ET might not require therapy while aspirin therapy is advised for low-risk disease. Cytoreductive therapy is recommended for high-risk ET and PV but it is not mandatory for intermediate-risk ET. First-line drug of choice for cytoreductive therapy, in both ET and PV, is hydroxyurea and second-line drugs of choice are interferon-α and busulfan. We do not recommend treatment with ruxolutinib in PV, unless in the presence of severe and protracted pruritus or marked splenomegaly that is not responding to the aforementioned drugs., (© 2018 Wiley Periodicals, Inc.)

This review focuses on the management of elderly patients with chronic myeloid leukemia and chronic myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and primary myelofibrosis. Median age in these neoplasms is within the 6th decades of age. All new therapies can be done at any age without absolute contraindication. However, the selection of the precise therapy for the single patient is mandatory. For these reasons, an accurate definition of diagnosis and prognostication is necessary. Precision in disease definition and prognostication is definitively helpful for personalizing therapeutic approach., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Current guidelines recommend therapeutic phlebotomy for all polycythemia vera (PV) patients and additional cytoreductive therapy (eg, hydroxyurea [HU]) for high-risk PV patients. Little is known about the impact of these therapies in the real-world setting. We conducted a retrospective cohort study of older adults diagnosed with PV from 2007 to 2013 using the linked Surveillance, Epidemiology, and End Results-Medicare database. Multivariable Cox proportional hazards models were used to assess the effect of phlebotomy and HU on overall survival (OS) and the occurrence of thrombotic events. Of 820 PV patients (median age = 77 years), 16.3% received neither phlebotomy nor HU, 23.0% were managed with phlebotomy only, 19.6% with HU only, and 41.1% with both treatments. After a median follow-up of 2.83 years, 37.2% (n = 305) of the patients died. Phlebotomy (yes/no; hazard ratio [HR] = 0.65; 95% confidence interval [CI], 0.51-0.81; P < .01), increasing phlebotomy intensity (HR = 0.71; 95% CI, 0.65-0.79; P < .01), and a higher proportion of days covered (PDC) by HU were all significantly associated with lower mortality. When thrombosis was the outcome of interest, phlebotomy (yes/no; HR = 0.52; 95% CI, 0.42-0.66; P < .01) and increasing phlebotomy intensity (HR = 0.46; 95% CI, 0.29-0.74; P < .01) were significantly associated with a lower risk of thrombotic events, so was a higher HU PDC. In this population-based study of older adults with PV reflecting contemporary clinical practice, phlebotomy and HU were associated with improved OS and decreased risk of thrombosis. However, both treatment modalities were underused in this cohort of older PV patients., (© 2018 by The American Society of Hematology.)

Background: Patients with polycythemia vera (PV) often experience symptoms that adversely affect their quality of life (QoL). The ongoing, prospective, observational REVEAL (Prospective Observational Study of Patients With Polycythemia Vera in US Clinical Practices) study was designed to collect contemporary data regarding burden of disease, clinical management, patient-reported outcomes (PROs), and health care resource utilization from adult patients with PV in the United States., Patients and Methods: Data on PROs were collected at enrollment using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS; range, 0-100); the European Organization for Research and Treatment of Cancer-Core Quality of Life Questionnaire, version 3.0 (EORTC QLQ-C30; range, 0-100); and the Work Productivity and Activity Impairment Questionnaire-Specific Health Problem (WPAI-SHP; range, 0%-100%)., Results: Among 2309 patients, mean (SD) disease duration was 5.8 (6.1) years and Charlson Comorbidity Index was 3.4 (0.8); 54.0% (1247/2309) were male. Mean (SD) MPN-SAF TSS was 18.8 (15.5). The most common symptoms were fatigue (80.1% [1844/2302]), early satiety (60.9% [1402/2302]), and inactivity (57.6% [1324/2302]). The most common severe symptoms were fatigue (16.8% [387/2302]), itching (13.4% [308/2302]), and inactivity (11.8% [271/2302]). The mean (SD) EORTC QLQ-C30 global health status/QoL score was 73.1 (23.2): mean functional subscale scores ranged from 80.5 (23.9) for cognitive functioning to 85.7 (24.6) for social functioning. The mean WPAI-SHP activity impairment score was 19.7% (n = 2300). Employed patients had mean WPAI-SHP scores for absenteeism, presenteeism, and overall work impairment of 3.2% (n = 810), 12.1% (n = 807), and 13.4% (n = 802), respectively., Conclusion: These data confirm that many patients with PV experience symptoms, QoL impairments, and work productivity impairments that negatively affect their lives. Longitudinal data from REVEAL will be important for evaluating how PROs change over time in these patients., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Very important developments related to polycythemia vera (PV) have occurred during the last two decades. The discovery of Janus kinase (JAK) 2 mutations has changed both the diagnosis and clinical management of PV. Currently JAK2 molecular testing is essential in the diagnostic work-up and JAK2 mutation positivity is a major diagnostic criterion. The discovery of JAK2 mutations suggested that abnormal JAK-STAT signaling was a pivotal feature in the pathogenesis of Philadelphia-negative myeloproliferative neoplasms. This idea led to the development of JAK inhibitors. Currently ruxolitinib, a JAK1/JAK2 inhibitor, is also approved for PV patients with hydroxyurea resistance or intolerance. International collaborations have made it possible to describe disease characteristics and evolution better. Presently it is possible to quantify the symptomatic burden of the disease and to estimate prognosis. In spite of these developments, management of PV still largely depends on estimation of thromboembolic risk and trying to decrease the risk with or without cytoreductive medications. Different approaches have been proposed by international disease experts for the diagnosis, thromboembolic risk estimation, and drug selection. This paper aims to review clinical aspects of PV and propose a management algorithm. The authors also point to still unresolved questions and unmet needs in diagnosis and management.

Therapy in Polycythemia Vera (PV), a myeloproliferative neoplasm, focuses on reducing cardiovascular (CV) risk without increasing bleeding or hematological progression. However, the real-world practice of treating PV in North America is understudied. We performed a retrospective cohort study of newly diagnosed PV (JAK2V617F mutation positive) patients in Hamilton, Canada to fill this knowledge gap. Out of 108 patients included, (n = 45, 41.7%) patients did not receive therapy consistent with contemporary treatment guidelines. Multivariable analysis showed increased white blood cell count at diagnosis (HR, 1.09; 95% CI, 1.04-1.14; p < 0.001), older age (HR, 1.15; 95% CI, 1.07-1.23; p < 0.001) and diabetic history (HR, 3.71; 95% CI, 1.27-10.78; p = 0.012) associated with greater mortality. Not receiving pharmacological treatment according to guidelines was also independently associated with increased mortality (HR, 3.12; 95% CI, 1.13-8.65; p = 0.029)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased thrombotic and cardiovascular risk, which are key contributors to patient morbidity and mortality. The Veterans Health Administration (VHA) is the largest integrative health network in the United States. Available data concerning patients with PV in this population are limited., Methods: This retrospective observational study evaluated the characteristics, management, and outcomes of patients with PV in the VHA Medical SAS® Dataset (October 1, 2005, to September 30, 2012). Inclusion criteria were ≥ 2 claims for PV (ie, PV diagnostic code was recorded) ≥30 days apart during the identification period, age ≥ 18 years, and continuous health plan enrollment from ≥12 months before the index date until the end of follow-up. All data were analyzed using descriptive statistics., Results: The analysis included 7718 patients (median age, 64 years; male, 98%; white, 64%). The most common comorbidities before the index date were hypertension (72%), dyslipidemia (54%), and diabetes (24%); 33% had a history of smoking. During the follow-up period (median, 4.8 years), most patients did not receive treatment with cytoreductive therapy, including phlebotomy (53%), or antiplatelet agents, such as aspirin (57%). The thrombotic and cardiovascular event rates per 1000 patient-years were 60.5 and 83.8, respectively. Among patients who received cytoreductive treatment, the thrombotic event rate was 48.9 per 1000 patient-years. The overall mortality rate was 51.2 per 1000 patient-years., Conclusion: The notable rates of thrombotic and cardiovascular events observed in this analysis, even among patients receiving cytoreductive treatment, highlight the important unmet clinical needs of patients with PV in the VHA.

Aquagenic pruritus is one of the main clinical features of polycythemia vera. The aim of this study was to analyse the clinical characteristics of aquagenic pruritus. The study group comprised 102 patients with molecularly confirmed polycythemia vera. Demographic data, data on disease history, polycythemia vera status and treatment modalities were collected. Moreover, various clinical features of aquagenic pruritus (including intensity, localization, quality, descriptors) and the most common factors responsible for its aggravation or alleviation were examined. Aquagenic pruritus was observed in 41.2% of individuals, mean duration 6.6 ± 8.6 years, and its onset was noticed in the majority of patients (52.4%) before the diagnosis of polycythemia vera. The mean intensity of aquagenic pruritus was 4.8 ± 1.9 points (visual analogue scale). One-third of patients with aquagenic pruritus avoided any contact with water. Antipruritic treatment was received only by 3 patients. Aquagenic pruritus seems to be an important, but frequently neglected, symptom in patients with polycythemia vera.

Objective: The current survey aimed to gather predefined disease parameters and treatment strategies to characterize the polycythemia vera (PV) patient population in Belgium., Methods: Cross-sectional data from PV patients, seen at least once between May 2014 and May 2015 at 10 sites in Belgium, were collected in aggregated form and analyzed descriptively and quantitatively., Results: Data from 343 PV patients were collected. Of these, 174 (50.7%) were male and 256 (74.6%) were ≥60 years of age. Ninety-two (26.8%) had a prior history of thrombotic events. Considerable proportions of patients had increased hematological parameters (hematocrit > 45% [31.2%], leukocytes > 10 × 10 9 /L [33.3%], and platelet > 400 × 10 9 /L [38.2%]). Most patients had non-palpable spleen (284, 87.7%) and no phlebotomies during the past 6 months (197, 57.4%). Low-dose aspirin was given as thrombosis prophylaxis in 249 (72.6%) patients, while 232 (67.6%) received hydroxyurea (HU) as cytoreductive treatment. Forty-one patients (12.0%) were reported as resistant and/or intolerant to HU. Seventeen patients (5.0%) received ruxolitinib in the context of clinical trials., Conclusion: This survey provides better insight into the characteristics of Belgian PV patients and currently used treatment strategies. It shows that 232 (67.6%) PV patients continue to receive HU despite being potentially HU-resistant., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Ruxolitinib was well tolerated and superior to best available therapy (including interferon [IFN]) in controlling hematocrit without phlebotomy eligibility, normalizing blood counts, and improving polycythemia vera-related symptoms in the Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care (RESPONSE) studies. This ad hoc analysis focuses on ruxolitinib in relation to IFN in the RESPONSE studies, with attention on the following: (1) safety and efficacy of ruxolitinib and best available therapy in patients who received IFN before study randomization, (2) safety and efficacy of IFN during randomized treatment in best available therapy arm, and (3) use of ruxolitinib after crossover from best available therapy in IFN-treated patients. IFN exposure before randomization had little effect on the efficacy or safety of ruxolitinib. In the randomized treatment arms, ruxolitinib was superior to IFN in efficacy [hematocrit control (RESPONSE = 60% of ruxolitinib vs 23% of IFN patients; RESPONSE-2 = 62% of ruxolitinib vs 15% of IFN patients)] and was tolerated better in hydroxyurea-resistant or hydroxyurea-intolerant patients. After crossing over to receive ruxolitinib, patients who had initially received IFN and did not respond had improved hematologic and spleen responses (62% of patients at any time after crossover) and an overall reduction in phlebotomy procedures. Rates and incidences of the most common adverse events decreased after crossover to ruxolitinib, except for infections (primarily grade 1 or 2). These data suggest that ruxolitinib is efficacious and well tolerated in patients who were previously treated with IFN. The RESPONSE (NCT01243944) and RESPONSE-2 (NCT02038036) studies were registered at clinicaltrials.gov .

Purpose of Review: To describe an algorithm-based approach, whenever available, to the diagnosis, the risk stratification criteria informing therapy and the current management of polycythemia vera and essential thrombocythemia., Recent Findings: Description of recurrent genetic abnormalities in driver genes, including Janus Kinase 2 (JAK2), myeloproliferative leukemia and calreticulin, a better appreciation of the key diagnostic role of bone marrow features, results of large epidemiologic studies and a few but landmark controlled clinical trials produced in the last decade, all resulted in a reappraisal of the approach to polycythemia vera and essential thrombocythemia., Summary: The revised 2017 WHO classification of polycythemia vera and essential thrombocythemia allows early diagnosis and accurate distinction from other chronic myeloproliferative neoplasms, particulary prefibrotic myelofibrosis. The prognostic value of selected mutations is being appreciated and JAK2V617F mutation is currently incorporated as risk variable in prognostic system for essential thrombocythemia. Risk-adjusted stratification is used to select therapeutic approaches that include target agents. However, there is not yet a curative approach to these hematologic neoplasms, and although their management has much improved in the last decades, the associated morbidity and mortality remains significant and may be worsened by toxicities of therapeutic agents. Therefore, several clinically relevant endpoints remain unmet.

Severe thrombocytopenia (platelets <50 × 10 9 /L) is associated with very poor outcome of patients with myelofibrosis (MF). As patients with primary myelofibrosis (PMF) differ from patients with postessential thrombocythemia (PET-MF) and postpolycythemia vera myelofibrosis (PPV-MF), we aimed to evaluate the significance of low platelets among these patients. We present clinical characteristics and outcome of patients with either PMF, PPV-MF, or PET-MF, and thrombocytopenia who presented to our institution between 1984 and 2015. Of 1269 patients (877 PMF, 212 PPV-MF, 180 PET-MF), 11% and 14% had platelets either <50 × 10 9 /L or between 50-100 × 10 9 /L, respectively. Patients with platelets <50 × 10 9 /L were most anemic and transfusion dependent, had highest blast count and unfavorable karyotype. In general, their overall and leukemia-free survival was the shortest with median time of 15 and 13 months, respectively; with incidence of acute leukemia almost twice as high as in the remaining patients (6.9 vs 3.6 cases per 100 person-years). Nevertheless, this observation remains mostly significant for patients with PMF, as those with PEV/PVT-MF have already significantly inferior prognosis with platelets <100 × 10 9 /L., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Polycythemia Vera (PV) and Essential Thrombocythemia (ET) are the most frequent Philadelphia chromosome-negative myeloproliferative neoplasms, the other entity being myelofibrosis. Management of patients with PV and ET is fraught with difficulties as they have an inherent tendency to cause thrombotic and hemorrhagic events. There are no curative treatment options, therefore it is important that a risk-adapted treatment approach is applied. Areas covered: This review discusses existing literature about prognosis in PV and ET, and addresses critical aspects related to defining 'high-risk' disease. In addition to the traditional risk factors such as age and prior thrombotic history, we discuss the prognostic impact of additional parameters such as cardiovascular risk factors, white blood cell count, karyotype and gene mutations. Expert commentary: We use age>60 years, presence of JAK2 mutation and a prior thrombotic history as the principle determinants of 'high-risk' for thrombosis in PV and ET, dividing the patients into very-low, low, intermediate and high-risk disease. Typically, low-risk patients are treated either with observation or aspirin alone. High-risk patients require cytoreductive therapies, along with aspirin and/or systemic anticoagulation. Intermediate-risk patients are treated on a case-by-case basis. Further, we aim to maintain a hematocrit <45% with aggressive phlebotomy in patients with PV.

Aquagenic pruritus (AP) has a significant influence on quality of life (QoL) in patients with polycythaemia vera. This study analysed the impact of AP on patient well-being in 102 patients with polycythaemia vera. Intensity of pruritus was evaluated using a visual analogue scale (VAS), verbal rating scale (VRS) and a 4-item Itch Questionnaire. Psychosocial aspects of AP were assessed with the Hospital Anxiety and Depression Scale (HADS), EQ-5D and itch-specific QoL questionnaire (ItchyQoL). AP of mean duration 6.6 ± 8.6 years and intensity 4.8 ± 1.9 points (VAS) was present in 42/102 individuals. The prevalence of depression and anxiety among patients with AP was 23.8% and 9.5%, respectively. Depression was more frequent in the AP group (vs. non-AP). Moreover, patients with AP had higher HADS-anxiety scoring than those without pruritus (p = 0.005). A negative correlation was found between duration of AP and EQ-5D-VAS. The ItchyQol score of 37.3 ± 12.3 points was influenced by the extent (p =0.01) and duration of episodes of AP (p = 0.02). In conclusion, AP places an additional burden on patients with polycy-thaemia vera, negatively influencing their QoL.

Recently reported mature survival data have confirmed the favorable prognosis in polycythemia vera (PV), with an estimated median survival of 24 years, in patients younger than age 60 years old. Currently available drugs for PV have not been shown to prolong survival or alter the natural history of the disease and are instead indicated primarily for prevention of thrombosis. Unfortunately, study endpoints that are being utilized in currently ongoing clinical trials in PV do not necessarily target clinically or biologically relevant outcomes, such as thrombosis, survival, or morphologic remission, and are instead focused on components of disease palliation. Even more discouraging has been the lack of critical appraisal from "opinion leaders", on the added value of newly approved drugs. Keeping these issues in mind, at present, we continue to advocate conservative management in low-risk PV (phlebotomy combined with once- or twice-daily aspirin therapy) and include cytoreductive therapy in "high-risk" patients; in the latter regard, our first, second, and third line drugs of choice are hydroxyurea, pegylated interferon-α and busulfan, respectively. In addition, it is reasonable to consider JAK2 inhibitor therapy, in the presence of protracted pruritus or markedly enlarged splenomegaly shown to be refractory to the aforementioned drugs.