Management of symptoms in polycythemia vera and essential thrombocythemia patients

Abstract The BCR-ABL-negative myeloproliferative neoplasms (MPNs) are clonal stem cell derived malignancies, which include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). The MPNs are characterized by dysregulated JAK-STAT signaling pathways. PV and ET are associated with an increased risk of thrombo-hemorrhagic complications, risk of progression to MF and leukemia. Presentation of patients with PV and ET is variable and usually as a result of abnormal full blood count indices (raised hemoglobin and hematocrit, leukocytosis, and thrombocytosis). Presentation with thrombosis or splenomegaly occurs in ∼30% of patients. Historically thought of as indolent compared with MF, patients with PV and ET have significant disease symptom burden which does not directly correlate to the current clinical prognostic classifications. The mainstay of therapy is reserved for patients with high-risk disease and thus excludes a population of patients with significant symptom related morbidity impacting their quality-of-life and survival. Recent treatment strategies have aimed to incorporate disease burden assessment into the selection of therapeutic interventions such as JAK2 inhibitors and HDAC inhibitors. We will review the advances in the field of MPN symptom assessment and symptom burden experienced by ET and PV patients. We will also discuss the risk-stratified management of ET and PV patients alongside symptom assessment and the impact of potential novel therapies, for patients who fail to respond to conventional treatment.

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Thrombocytosis: Diagnostic Evaluation, Thrombotic Risk Stratification, and Risk-Based Management Strategies

Thrombosis ◽

10.1155/2011/536062 ◽

2011 ◽

Vol 2011 ◽

pp. 1-16 ◽

Cited By ~ 43

Author(s):

Jonathan S. Bleeker ◽

William J. Hogan

Keyword(s):

Polycythemia Vera ◽

Essential Thrombocythemia ◽

Myeloproliferative Neoplasms ◽

Treatment Options ◽

Treatment Strategies ◽

Diagnostic Evaluation ◽

Diagnostic Process ◽

Special Focus ◽

Thrombotic Risk ◽

Increased Risk

Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera.

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What are the current treatment approaches for patients with polycythemia vera and essential thrombocythemia?

Hematology ◽

10.1182/asheducation-2017.1.480 ◽

2017 ◽

Vol 2017 (1) ◽

pp. 480-488 ◽

Cited By ~ 6

Author(s):

Alessandro M. Vannucchi ◽

Paola Guglielmelli

Keyword(s):

Polycythemia Vera ◽

Essential Thrombocythemia ◽

State Of The Art ◽

Myeloproliferative Neoplasms ◽

Symptom Burden ◽

Current Treatment ◽

Interferon Α ◽

Jak2 Inhibitor ◽

Chronic Myeloproliferative Neoplasms

Abstract Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative neoplasms that are characterized by thrombohemorrhagic complications, symptom burden, and impaired survival mainly due to thrombosis, progression to myelofibrosis, and transformation to acute leukemia. In this manuscript, we will review the most recent changes in diagnostic criteria, the improvements in risk stratification, and the “state of the art” in the daily management of these disorders. The role of conventional therapies and novel agents, interferon α and the JAK2 inhibitor ruxolitinib, is critically discussed based on the results of a few basic randomized clinical studies. Several unmet needs remain, above all, the lack of a curative approach that might overcome the still burdensome morbidity and mortality of these hematologic neoplasms, as well as the toxicities associated with therapeutic agents.

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Splenomegaly impacts prognosis in essential thrombocythemia and polycythemia vera: A single center study

Hematology Reports ◽

10.4081/hr.2019.8281 ◽

2019 ◽

Vol 11 (4) ◽

Cited By ~ 2

Author(s):

Vincenzo Accurso ◽

Marco Santoro ◽

Simona Raso ◽

Angelo Davide Contrino ◽

Paolo Casimiro ◽

...

Keyword(s):

Polycythemia Vera ◽

Essential Thrombocythemia ◽

Myeloproliferative Neoplasms ◽

Clinical Manifestations ◽

Primary Myelofibrosis ◽

Thrombotic Risk ◽

Single Center Study ◽

The Impact ◽

The Relationship

Splenomegaly is one of the major clinical manifestations of primary myelofibrosis and is common also in other chronic Philadelphia-negative myeloproliferative neoplasms, causing symptoms and signs and affecting quality of life of patients diagnosed with these diseases. We aimed to study the impact that such alteration has on thrombotic risk and on the survival of patients with essential thrombocythemia and patients with Polycythemia Vera (PV). We studied the relationship between splenomegaly (and its grade), thrombosis and survival in 238 patients with et and 165 patients with PV followed at our center between January 1997 and May 2019.

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Increased risks of polycythemia vera, essential thrombocythemia, and myelofibrosis among 24 577 first-degree relatives of 11 039 patients with myeloproliferative neoplasms in Sweden

Blood ◽

10.1182/blood-2008-03-143602 ◽

2008 ◽

Vol 112 (6) ◽

pp. 2199-2204 ◽

Cited By ~ 146

Author(s):

Ola Landgren ◽

Lynn R. Goldin ◽

Sigurdur Y. Kristinsson ◽

Elin A. Helgadottir ◽

Jan Samuelsson ◽

...

Keyword(s):

Polycythemia Vera ◽

Essential Thrombocythemia ◽

Myeloid Leukemia ◽

Myeloproliferative Neoplasms ◽

Familial Aggregation ◽

Susceptibility Gene ◽

Degree Relative ◽

First Degree Relatives ◽

Relative Risks ◽

Increased Risk

Abstract Previous small studies have reported familial clustering of myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). We identified 6217 PV, 2838 ET, 1172 MF, and 812 MPN unclassifiable (NOS) patients diagnosed in Sweden, 43 550 controls, and first-degree relatives of cases (n = 24 577) and controls (n = 99 542). Using a marginal survival model, we calculated relative risks (RRs) and 95% confidence intervals as measures of familial aggregation. Relatives of MPN patients had significantly increased risks of PV (RR = 5.7; 3.5-9.1), ET (RR = 7.4; 3.7-14.8), and MPN NOS (RR = 7.5; 2.7-20.8). Analyses stratified by type of first-degree relative revealed consistently higher risks for siblings, compatible with a model of recessive genetic inheritance, which can be confirmed only by identifying the susceptibility gene(s). Mean age at MPN diagnosis was not different (P = .20) for affected relatives of cases (57.5 years) versus controls (60.6 years), and risk of MPN by age was not different for parents versus offspring of MPN cases (P = .10), providing no support for anticipation. Relatives of MPN patients had a borderline increased risk of chronic myeloid leukemia (CML; RR = 1.9; 0.9-3.8; P = .09). Our findings of 5- to 7-fold elevated risk of MPNs among first-degree relatives of MPN patients support the hypothesis that common, strong, shared susceptibility genes predispose to PV, ET, MF, and possibly CML.

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JAK2V617F mutation and hydroxyurea treatment as determinants of immature platelet parameters in essential thrombocythemia and polycythemia vera patients

Blood ◽

10.1182/blood-2011-02-339655 ◽

2011 ◽

Vol 118 (9) ◽

pp. 2599-2601 ◽

Cited By ~ 43

Author(s):

Marina Panova-Noeva ◽

Marina Marchetti ◽

Sabrina Buoro ◽

Laura Russo ◽

Annamaria Leuzzi ◽

...

Keyword(s):

Polycythemia Vera ◽

Essential Thrombocythemia ◽

Myeloproliferative Neoplasms ◽

Jak2v617f Mutation ◽

Favorable Effect ◽

Thrombotic Risk ◽

Mutational Status ◽

Hydroxyurea Treatment ◽

Increased Risk ◽

Hydroxyurea Therapy

Abstract Immature platelets (IPFs), which are hemostatically more active than mature platelets, have been found elevated in essential thrombocythemia and polycythemia vera, 2 myeloproliferative neoplasms (MPN) characterized by an increased risk of thrombosis. It is not known whether the IPF levels are influenced by pathogenetic factors, including JAK2V617F mutational status, or by treatment regimen. To address this point, in 46 essential thrombocythemia and 38 polycythemia vera consecutive patients, we measured IPF and correlated the results to JAK2V617F mutation and myelosuppressive treatment with hydroxyurea. This analysis provides 2 new elements regarding IPF and MPN. The first finding is that the JAK2V617F mutation is linked to the quantity of IPF in patients with MPN, which might contribute to the prothrombotic phenotype in these patients. The second finding is that IPF is susceptible to myelosuppressive treatment, which may additionally explain the favorable effect of hydroxyurea therapy on MPN outcome as well as the associated thrombotic risk.

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Is there a gender effect in polycythemia vera?

Annals of Hematology ◽

10.1007/s00277-020-04287-w ◽

2020 ◽

Vol 100 (1) ◽

pp. 11-25

Author(s):

Francesca Palandri ◽

Barbara Mora ◽

Naseema Gangat ◽

Lucia Catani

Keyword(s):

Polycythemia Vera ◽

Clinical Presentation ◽

Myeloproliferative Neoplasms ◽

Treatment Strategies ◽

Gender Effect ◽

Thrombotic Risk ◽

Chronic Myeloproliferative Neoplasms ◽

Disease Biology ◽

Systemic Symptoms ◽

The Impact

AbstractIn recent times, there has been a growing interest in understanding the impact of gender on disease biology and clinical outcomes in Philadelphia-negative chronic myeloproliferative neoplasms. Among those, polycythemia vera (PV) is characterized by increased thrombotic risk, systemic symptoms, and overall reduced survival. Here, we aim to summarize data on whether and to what extent female sex can affect PV biology and outcome. To this end, we will discuss the latest acquisitions in terms of pathogenesis, diagnosis, epidemiology, clinical presentation and symptoms burden, thrombotic risk and related treatment strategies, and prognosis in female patients affected by PV.

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The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): International Prospective Validation and Reliability Trial in 402 patients

Blood ◽

10.1182/blood-2011-01-328955 ◽

2011 ◽

Vol 118 (2) ◽

pp. 401-408 ◽

Cited By ~ 175

Author(s):

Robyn Scherber ◽

Amylou C. Dueck ◽

Peter Johansson ◽

Tiziano Barbui ◽

Giovanni Barosi ◽

...

Keyword(s):

Quality Of Life ◽

Polycythemia Vera ◽

Essential Thrombocythemia ◽

Myeloproliferative Neoplasms ◽

Intraclass Correlation ◽

Myeloproliferative Neoplasm ◽

Symptom Assessment ◽

The United States ◽

Life Questionnaire

Abstract Symptomatic burden in myeloproliferative neoplasms is present in most patients and compromises quality of life. We sought to validate a broadly applicable 18-item instrument (Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF], coadministered with the Brief Fatigue Inventory) to assess symptoms of myelofibrosis, essential thrombocythemia, and polycythemia vera among prospective cohorts in the United States, Sweden, and Italy. A total of 402 MPN-SAF surveys were administered (English [25%], Italian [46%], and Swedish [28%]) in 161 patients with essential thrombocythemia, 145 patients with polycythemia vera, and 96 patients with myelofibrosis. Responses among the 3 administered languages showed great consistency after controlling for MPN subtype. Strong correlations existed between individual items and key symptomatic elements represented on both the MPN-SAF and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30. Enrolling physicians' blinded opinion of patient symptoms (6 symptoms assessed) were highly correlated with corresponding patients' responses. Serial administration of the English MPN-SAF among 53 patients showed that most MPN-SAF items are well correlated (r > 0.5, P < .001) and highly reproducible (intraclass correlation coefficient > 0.7). The MPN-SAF is a comprehensive and reliable instrument that is available in multiple languages to evaluate symptoms associated with all types of MPNs in clinical trials globally.

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Tobacco use in the Myeloproliferative neoplasms: symptom burden, patient opinions, and care

BMC Cancer ◽

10.1186/s12885-021-08439-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Sarah F. Christensen ◽

Robyn M. Scherber ◽

Gina L. Mazza ◽

Amylou C. Dueck ◽

Nana Brochmann ◽

...

Keyword(s):

Quality Of Life ◽

Tobacco Use ◽

Myeloproliferative Neoplasms ◽

Myeloproliferative Neoplasm ◽

Symptom Burden ◽

Symptom Assessment ◽

Cross Sectional ◽

Former Smokers ◽

Never Smokers

Abstract Background Patients with Philadelphia-negative Myeloproliferative Neoplasms (MPN) suffer from numerous symptoms and decreased quality of life. Smoking is associated with an increased symptom burden in several malignancies. The aim of this study was to analyze the association between smoking and MPN-related symptom burden and explore MPN patients’ opinions on smoking. Methods A total of 435 patients with MPN participated in a cross-sectional internet-based survey developed by the Mayo Clinic and the Myeloproliferative Neoplasm Quality of Life Group. Patients reported their demographics, disease characteristics, tobacco use, and opinions on tobacco use. In addition, MPN-related symptoms were reported via the validated 10-item version of the Myeloproliferative Neoplasms Symptom Assessment Form. Results Current/former smokers reported worse fatigue (mean severity 5.6 vs. 5.0, p = 0.02) and inactivity (mean severity 4.0 vs. 3.4, p = 0.03) than never smokers. Moreover, current/former smokers more frequently experienced early satiety (68.5% vs. 58.3%, p = 0.03), inactivity (79.9% vs. 71.1%, p = 0.04), and concentration difficulties (82.1% vs. 73.1%, p = 0.04). Although not significant, a higher total symptom burden was observed for current/former smokers (mean 30.4 vs. 27.0, p = 0.07). Accordingly, overall quality of life was significantly better among never smokers than current/former smokers (mean 3.5 vs. 3.9, p = 0.03). Only 43.2% of the current/former smokers reported having discussed tobacco use with their physician, and 17.5% did not believe smoking increased the risk of thrombosis. Conclusion The current study suggests that smoking may be associated with increased prevalence and severity of MPN symptoms and underscores the need to enhance patient education and address tobacco use in the care of MPN patients.

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Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions

Journal of Clinical Medicine ◽

10.3390/jcm10040835 ◽

2021 ◽

Vol 10 (4) ◽

pp. 835

Author(s):

Manoja P. Herath ◽

Jeffrey M. Beckett ◽

Andrew P. Hills ◽

Nuala M. Byrne ◽

Kiran D. K. Ahuja

Keyword(s):

Diabetes Mellitus ◽

Adipose Tissue ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Fat Mass ◽

Metabolic Disorders ◽

Later Life ◽

Therapeutic Interventions ◽

Increased Risk ◽

The Impact

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.

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Living with an MPN in Ireland: patients' and caregivers' perspectives

British Journal of Nursing ◽

10.12968/bjon.2021.30.17.s24 ◽

2021 ◽

Vol 30 (17) ◽

pp. S24-S30

Author(s):

Geraldine Walpole ◽

Mary Kelly ◽

Joy Lewis ◽

Avril Gleeson ◽

Ann-Marie Cullen ◽

...

Keyword(s):

Quality Of Life ◽

Unmet Needs ◽

Negative Impact ◽

Peer Group ◽

Myeloproliferative Neoplasms ◽

Symptom Burden ◽

Emotional Wellbeing ◽

The Republic ◽

The Impact

Myeloproliferative neoplasms (MPNs) are associated with a high disease burden, reduced quality of life and shortened survival. The aim of this questionnaire was to gain patients' and caregivers' perspectives on the impact of living with an MPN in the Republic of Ireland. An Irish adaptation of the ‘Global MPN Landmark survey’ was conducted. Fifty-one patients and 44 caregivers completed the questionnaire. Patients reported a wide variety of symptoms at the time of questionnaire completion; fatigue, bone pain and pruritus being most frequently reported. Approximately one-third of respondents from each of the groups (patients and caregivers) reported a negative impact of MPNs on their emotional wellbeing and daily lives. The study findings revealed that, despite treatment, symptom burden remains high, and several unmet needs exist, including educational, emotional and peer group support. Interventions that focus on reducing symptom burden and addressing these unmet needs, may improve the quality of life for patients with MPNs and their caregivers.

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