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

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 480-488 ◽  
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.

Clinical Factors Predictive Of Myelofibrotic Evolutions In Patients With Essential Thrombocythemia and Polycythemia Vera

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4082-4082 ◽  
Author(s):  
Mario Tiribelli ◽  
Federico De Marchi ◽  
Daniela Barraco ◽  
Luciana Marin ◽  
Erika Codarin ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Clinical Feature ◽  
Baseline Characteristics ◽  
Wbc Count ◽  
Prognostic Risk Factors

Abstract Introduction Evolution to myelofibrosis (MF) represents a relatively rare but always severe event in patients with essential thrombocythemia (ET) and polycythemia vera (PV). Few reports have focused on the clinical and biological features at diagnosis of ET and PV that correlate with progression to MF. Aims and Methods We retrospectively studied a series of patients with post-ET and post-PV MF and compared with a group of ET and PV patients with a long follow-up without myelofibrotic evolution, with the aim to identify prognostic factors for MF. Forty-three patients with post-ET (n=29) and post-PV (n=14) MF followed at our institution were compared with 125 ET and 75 PV patients with at least 9 years of follow-up without evolution. Diagnosis of ET and PV was confirmed according to WHO criteria (including JAK2 analysis, performed since 2006 and study), evolution to MF was defined according to IWG-MRT proposed criteria. The following parameters, available for all patients at diagnosis of ET or ET, were taken into consideration to find prognostic risk factors for myelofibrosis: age, platelet (PLT) count, hemoglobin (Hb) and hematocrit (Hct) levels, white blood cell (WBC) count. Statistical analyses were conducted using Student t test. Results Median time from diagnosis of ET/PV and progression to MF was 156 months (range: 29-314). Comparing baseline characteristics of patients who evolved to MF and those who did not, we did not found any significant correlation. Mean data at diagnosis for patients with (n = 43) or without (n=200) subsequent evolution to MF were as follow: age 52.1 vs 53.1 years (p=0.79), Hb 15.4 vs 15.7 g/dl (p=0.59), Hct 47.2 vs 47.1% (p=0.67), WBC 9.8 vs 9.1 x 109/l (p=0.11), PLT 713 vs 689 x 109/l (p=0.87). Also when considering only the 29 post-ET MF and the 125 ET patients, there was no clinical feature present at diagnosis that could foresee a future myelofibrotic evolution. Conversely, in the 14 post-PV MF and 75 PV patients, progression to MF was predicted only by higher WBC count (11.4 vs 9.3 x 109/l, p=0.046), while no correlation was found with age, Hb, Hct or PLT [Table 1]. Conclusions Concordant with some previous reports, our data suggest a possible role of leucocytosis as an adverse risk factor for progression to MF in patients with PV, though not in ET. Other clinical characteristics present at diagnosis, such as advanced age, anemia or polycythemia and thrombocytosis do not seem to be associated with higher risk of fibrotic evolution in patients with myeloproliferative neoplasms. Disclosures: No relevant conflicts of interest to declare.

Role of JAK2 V617F mutation and aberrant expression of microRNA-143 in myeloproliferative neoplasms

2015 ◽  
Vol 53 (7) ◽  
Author(s):  
Marco Benati ◽  
Martina Montagnana ◽  
Elisa Danese ◽  
Giovanna De Matteis ◽  
Dino Veneri ◽  
...  
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Blood Cells ◽  
Healthy Subjects ◽  
Myeloproliferative Neoplasms ◽  
Jak2 V617f ◽  
Idiopathic Myelofibrosis ◽  
Aberrant Expression ◽  
Who 2008

AbstractMyeloproliferative neoplasms (MPNs) are clonal myeloid disorders characterized by the overproduction of mature blood cells. The pathogenetic hallmark of MPNs is the dysregulation of JAK-STAT signaling, usually associated with theIn total 78 patients with a clinical diagnosis of polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IM), made according to the WHO 2008 criteria, were included in the study. Twenty healthy subjects were checked as controls. Quantification ofThe miR-143 expression in MPNs patients was 2.97-fold higher than in controls.Our findings of aberrant miR-143 expression support the concept that factors other than

scholarly journals Evaluation of Therapeutic Strategies to Reduce the Number of Thrombotic Events in Patients With Polycythemia Vera and Essential Thrombocythemia

2021 ◽  
Vol 10 ◽  
Author(s):  
Douglas Tremblay ◽  
Heidi E. Kosiorek ◽  
Amylou C. Dueck ◽  
Ronald Hoffman
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Clinical Trial Design ◽  
Surrogate Endpoint ◽  
Therapeutic Agents ◽  
Design Strategies ◽  
Inflammatory Milieu ◽  
Pathophysiologic Mechanisms

Thrombosis is the largest contributor to morbidity and mortality in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Our understanding of the risk factors and pathophysiology of thrombosis in PV and ET patients is developing, including recent insights into the role of aberrant platelet-neutrophil interactions, JAK2 mutated endothelial cells and the pro-thrombotic inflammatory milieu. To date, few available therapies have demonstrated the ability to reduce the thrombotic burden in patients with these diseases. Although numerous therapeutic agents have been investigated in both PV and ET patients, few studies are designed to assess their impact on thrombotic events. In this review, we first describe the burden of thrombosis in patients with these myeloproliferative neoplasms (MPNs) and briefly explore their pathophysiologic mechanisms. We then critically assess and summarize the evidence behind currently available therapies with attention toward thrombotic endpoints. Finally, we describe a path forward for clinical research in MPNs that involves surrogate endpoint validation, biomarker development, and clinical trial design strategies in order to accurately assess reduction of thrombotic events when evaluating novel therapies.

scholarly journals Management of symptoms in polycythemia vera and essential thrombocythemia patients

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 340-348 ◽  
Author(s):  
Deepti Radia ◽  
Holly L. Geyer
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Myeloproliferative Neoplasms ◽  
Treatment Strategies ◽  
Symptom Burden ◽  
Symptom Assessment ◽  
Therapeutic Interventions ◽  
Full Blood Count ◽  
Increased Risk ◽  
The Impact

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.

scholarly journals THE JAK2V617F POINT MUTATION INCREASES THE OSTEOCLAST FORMING ABILITY OF MONOCYTES IN PATIENTS WITH CHRONIC MYELOPROLIFERATIVE NEOPLASMS AND MAKES THEIR OSTEOCLASTS MORE SUSCEPTIBLE TO JAK2 INHIBITION

2018 ◽  
Vol 10 ◽  
pp. e2018058
Author(s):  
Emmanouil Spanoudakis ◽  
Menelaos Papoutselis ◽  
Ioanna Bazntiara ◽  
Eleftheria Lamprianidou ◽  
Xrisa Kordella ◽  
...  
Keyword(s):  
Point Mutation ◽  
Genomic Dna ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Cellular Level ◽  
Hemopoietic Stem Cell ◽  
Jak2 Inhibitor ◽  
Chronic Myeloproliferative Neoplasms ◽  
Cell Niche ◽  
Jak2 Inhibition

JAK2V617F is a gain of function point mutation that occurs in Myeloproliferative Neoplasm (MPN) patients and deranges their hemopoiesis at cellular level. We speculate that hyperfunctioning JAK2 can modify osteoclast (OCL) homeostasis in MPN patients. We studied 18 newly diagnosed MPN patients and four age-matched normal donors (ND). Osteoclast forming assays started from selected monocytes also and under titrated concentrations of the JAK2 Inhibitor AG-490 (Tyrphostin). Genomic DNA was extracted from the formed osteoclasts, and the JAK2V617F/JAK2WT genomic DNA ratio was calculated. OCLs formed from monocytes derived from heterozygous (Het) for the JAK2V617F mutation MPN patients, were three times more compared to those from JAK2 wild type (WT) MPN patients (p=0,05) and from ND as well (p=0,03). The ratio of JAK2V617F/JAK2WT genomic DNA was increased in OCLs compared to the input monocyte cells showing a survival advantage of the mutated clone. In comparison to ND and JAK2 WT MPN patients, OCLs from patients JAK2V617F (Het) were more susceptible to JAK2 inhibition. These alterations in osteoclast homeostasis, attributed to mutated JAK2, can deregulate the hemopoietic stem cell niche in MPN patients.

JAK inhibition in the myeloproliferative neoplasms: lessons learned from the bench and bedside

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 529-537 ◽  
Author(s):  
Jason Gotlib
Keyword(s):  
Myeloproliferative Neoplasms ◽  
Symptom Burden ◽  
Jak2 V617f ◽  
Lessons Learned ◽  
Jak Inhibitors ◽  
Jak2 Inhibitor ◽  
Sequencing Technologies ◽  
Cell Growth And Differentiation ◽  
Scientific Context ◽  
Generation Sequencing

AbstractThe discovery of the JAK2 V617F mutation in the classic BCR-ABL1–negative myeloproliferative neoplasms in 2005 catalyzed a burst of research efforts that have culminated in substantial dividends for patients. Beyond JAK2 V617F, a more detailed picture of the pathobiologic basis for activated JAK-STAT signaling has emerged. In some patients with myelofibrosis (MF), next-generation sequencing technologies have revealed a complex clonal architecture affecting both genetic and epigenetic regulators of cell growth and differentiation. Although these bench-top findings have informed the clinical development of JAK inhibitors in MF, they have also provided scientific context for some of their limitations. The JAK1/JAK2 inhibitor ruxolitinib is approved for treatment of MF in North America and Europe and other lead JAK inhibitors discussed herein (fedratinib [SAR302503], momelotinib [CYT387], and pacritinib [SB1518]), have entered advanced phases of trial investigation. Uniformly, these agents share the ability to reduce spleen size and symptom burden. A major challenge for practitioners is how to optimize dosing of these agents to secure clinically relevant and durable benefits while minimizing myelosuppression. Suboptimal responses have spurred a “return to the bench” to characterize the basis for disease persistence and to inform new avenues of drug therapy.

scholarly journals Leukocytosis and thrombosis in essential thrombocythemia and polycythemia vera: a systematic review and meta-analysis

2019 ◽  
Vol 3 (11) ◽  
pp. 1729-1737 ◽  
Author(s):  
Alessandra Carobbio ◽  
Alberto Ferrari ◽  
Arianna Masciulli ◽  
Arianna Ghirardi ◽  
Giovanni Barosi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Blood Cell ◽  
Polycythemia Vera ◽  
White Blood Cell ◽  
Essential Thrombocythemia ◽  
Recurrent Events ◽  
Myeloproliferative Neoplasms ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Cell Counts

Abstract 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.

scholarly journals Thrombotic disease in the myeloproliferative neoplasms

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 571-581 ◽  
Author(s):  
Anna Falanga ◽  
Marina Marchetti
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia ◽  
Protein C ◽  
Blood Clotting ◽  
Myeloproliferative Neoplasms ◽  
Philadelphia Chromosome ◽  
Activated Protein C ◽  
Vascular Cells ◽  
Antithrombotic Drugs ◽  
Inflammatory Stimuli

Abstract Thrombosis is a leading cause of morbidity and mortality in patients with Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs), particularly polycythemia vera and essential thrombocythemia. Mechanisms involved in the pathogenesis of the acquired thrombophilic state associated with these diseases include abnormalities of MPN clone–derived blood cells, which display prothrombotic features, and abnormalities of normal vascular cells, which become procoagulant in response to inflammatory stimuli. Ultimately, the release into the blood of elevated levels of procoagulant microparticles by platelets and vascular cells and the increase in the global thrombin generation due to an acquired activated protein C resistance result in a highly prothrombotic scenario in patients with polycythemia vera and essential thrombocythemia. The acquired point mutation in the pseudokinase domain of JAK2 (JAK2V617F) in these disorders is variably associated with thrombosis and, more consistently, with elevations in WBC counts and alterations in biomarkers of blood-clotting abnormalities. The predictive value of these biomarkers for thrombosis remains to be established to identify subsets of patients at elevated risk who may benefit from prophylaxis with antithrombotic drugs.

Treatment of Polycythemia Vera and Essential Thrombocythemia: The Role of Pipobroman

2003 ◽  
Vol 44 (9) ◽  
pp. 1483-1488 ◽  
Author(s):  
Francesco Passamonti ◽  
Mario Lazzarino
Keyword(s):  
Polycythemia Vera ◽  
Essential Thrombocythemia
Sign in / Sign up

Export Citation Format

Share Document