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Archives of Pathology & Laboratory... Aug 2006Polycythemia vera (PV) is a clonal myeloproliferative disease characterized by an erythroid dominant trilineage proliferation of hematopoietic precursor cells.... (Review)
Review
CONTEXT
Polycythemia vera (PV) is a clonal myeloproliferative disease characterized by an erythroid dominant trilineage proliferation of hematopoietic precursor cells. Classified as a chronic myeloproliferative disease, PV represents a histopathologic spectrum of 2 recognized stages, the polycythemic and postpolycythemic phase. The clinical manifestations of hemorrhage, thrombosis, and increased red cell mass are directly related to primary bone marrow dysfunction. Prognosis is strongly associated with thrombosis risk and disease progression; thus, treatment is directed toward minimizing coagulopathic complications and preventing leukemic transformation. Recently, a specific point mutation in the Janus kinase 2 (JAK2) gene was described in a majority of PV patients. The potential diagnostic and/or prognostic value of JAK2V617F is discussed.
OBJECTIVE
To review important developments from the recent and historical literature. Modern diagnostic criteria and emerging molecular findings are emphasized.
DATA SOURCES
A comprehensive review was performed of the relevant literature indexed in PubMed (National Library of Medicine) and referenced medical texts.
CONCLUSIONS
Modified clinical, histologic, and laboratory criteria have clarified the diagnosis of PV. Also, continuing studies on the recently discovered JAK2V617F gene mutation may significantly improve our understanding of PV pathogenesis and facilitate its medical management.
Topics: Biomarkers; Bone Marrow; Erythrocyte Volume; Hemorrhage; Humans; Janus Kinase 2; Point Mutation; Polycythemia Vera; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Thrombosis
PubMed: 16879013
DOI: 10.5858/2006-130-1126-PV -
Cleveland Clinic Journal of Medicine 1989The occurrence of polycythemia vera in a father, mother, and two sons is reported. Thirteen kindreds with familial polycythemia vera in 31 members are reviewed.... (Review)
Review
The occurrence of polycythemia vera in a father, mother, and two sons is reported. Thirteen kindreds with familial polycythemia vera in 31 members are reviewed. Comprehensive records were available for all four patients as well as other family members, since all were diagnosed and treated at the author's institution over a period of nearly 50 years. The mean age at diagnosis, sex predominance, symptoms, and incidence of chromosomal abnormalities, leukocytosis, thrombocytosis, and elevated leukocyte alkaline phosphatase levels were similar to those of nonfamilial cases. The mean RBC volume at diagnosis and the incidence of splenomegaly appear to be higher in familial than nonfamilial cases. The mode of inheritance is unclear, but genetic factors may be involved in the pathogenesis of this myeloproliferative disorder.
Topics: Aged; Cluster Analysis; Female; Humans; Male; Middle Aged; Ohio; Polycythemia Vera
PubMed: 2691118
DOI: 10.3949/ccjm.56.8.813 -
Annals of Hematology Oct 2022Hematological control, incidence of complications, and need for cytoreduction were studied in 453 patients with low-risk polycythemia vera (PV) treated with phlebotomies...
Low-risk polycythemia vera treated with phlebotomies: clinical characteristics, hematologic control and complications in 453 patients from the Spanish Registry of Polycythemia Vera.
Hematological control, incidence of complications, and need for cytoreduction were studied in 453 patients with low-risk polycythemia vera (PV) treated with phlebotomies alone. Median hematocrit value decreased from 54% at diagnosis to 45% at 12 months, and adequate hematocrit control over time (< 45%) was observed in 36%, 44%, and 32% of the patients at 6, 12, and 24 months, respectively. More than 5 phlebotomies per year in the maintenance phase were required in 19% of patients. Worsening thrombocytosis, age > 60 years, and microvascular symptoms constituted the main indications for starting cytoreduction. Median duration without initiating cytoreduction was significantly longer in patients younger than 50 years (< 0.0001). The incidence rate of thrombosis under phlebotomies alone was 0.8% per year and the estimated probability of thrombosis at 10 years was 8.5%. The probability of arterial thrombosis was significantly higher in patients with arterial hypertension whereas there was a trend to higher risk of venous thrombosis in cases with high JAK2V617F allele burden. Rates of major bleeding and second primary neoplasm were low. With a median follow-up of 9 years, survival probability at 10 years was 97%, whereas the probability of myelofibrosis at 10 and 20 years was 7% and 20%, respectively. Progression to acute myeloid leukemia was documented in 3 cases (1%). Current management of low-risk PV patients is associated with low rate of thrombosis and long survival. New treatment strategies are needed for improving hematological control and, in the long term, reducing progression to myelofibrosis.
Topics: Humans; Leukemia, Myeloid, Acute; Middle Aged; Phlebotomy; Polycythemia Vera; Primary Myelofibrosis; Registries; Thrombosis
PubMed: 36042023
DOI: 10.1007/s00277-022-04963-z -
Expert Opinion on Investigational Drugs Aug 2020Current treatment for polycythemia vera (PV) is limited and primarily targets thrombosis risk. Agents targeting distinct mechanisms of action within myeloproliferation... (Review)
Review
INTRODUCTION
Current treatment for polycythemia vera (PV) is limited and primarily targets thrombosis risk. Agents targeting distinct mechanisms of action within myeloproliferation are undergoing clinical evaluation to optimize efficacy, improve tolerance and augment long term disease complications.
AREA COVERED
This article reviews the current data from completed early phase clinical trials in PV, either as monotherapy or in combination with the few currently approved agents.
EXPERT OPINION
There remains an opportunity in PV management to improve efficacy and decrease risk of disease progression. Evolving data from use of long acting interferons are serving to clarifying the potential front line role of this therapy. JAK2 inhibition has made a significant impact on decreasing morbidity in patients with hydroxyurea resistant/refractory disease. New approaches may soon expand options including histone deactylase inhibitors (HDACi), either as monotherapy or combination therapy, which showed promising activity and symptomatic control of pruritus. Drugs targeting new molecular pathways (mammalian target of rapamycin, insulin receptor substrates 1/2, MDM2 protein) or the iron metabolism pathway are in early phase trial. Further translational studies assessing efficacy, long term complications, survival, and constitutional symptom control could pave a way for future success in PV drug development either as monotherapy or in combination.
Topics: Animals; Disease Progression; Drug Development; Histone Deacetylase Inhibitors; Humans; Hydroxyurea; Janus Kinase 2; Molecular Targeted Therapy; Polycythemia Vera
PubMed: 32552220
DOI: 10.1080/13543784.2020.1782886 -
Modern Pathology : An Official Journal... Nov 2015Polycythemia vera in 20-30% of cases progresses towards post-polycythemic myelofibrosis, an advanced phase characterized by decreased red blood cells counts and...
Polycythemia vera in 20-30% of cases progresses towards post-polycythemic myelofibrosis, an advanced phase characterized by decreased red blood cells counts and increasing splenomegaly with extramedullary hematopoiesis. There is evidence that the presence of neutrophilic leukocytosis at polycythemia vera disease outset is associated with an increased risk of recurrent thrombosis. However, its clinical significance when developing later in the course of the disease is not well defined. Over a period of 8 years we identified from the files of two reference centers 10 patients (7M/3F, median age: 68 years) who developed persistent absolute leukocytosis ≥ 13 × 10⁹/l (median: 25.1 × 10⁹/l; range: 16.1-89.7 × 10⁹/l) at or around the time of diagnosis of post-polycythemic myelofibrosis (median interval from diagnosis:0 months; range: -6/31) and persisted for a median period of 13 months. Peripheral blood smears showed numerous neutrophils without dysplastic features and, in four, ≥ 10% immature myeloid precursors. In five cases, corresponding marrow specimens obtained at or immediately after the onset of leukocytosis showed a markedly increased myeloid:erythroid ratio due to granulocytic proliferation. No change in JAK2 and BCR-ABL1 status or cytogenetic evolution was associated with the development of leukocytosis. The mutational status of CSF3R, SETBP1, and SRSF2, genes associated with other chronic myeloid neoplasms where neutrophilic leukocytosis occurs, was investigated but all cases showed wild-type only alleles. Four patients died after developing leukocytosis and one experienced worsening disease. Compared with a control group of post-polycythemic myelofibrosis patients (n=23) who never developed persistent leukocytosis, patients with leukocytosis showed higher white blood cells counts and a shorter overall survival. This is the first study describing the development of significant neutrophilic leukocytosis during advanced stages of polycythemia vera; it includes comprehensive hematologic, marrow morphological, molecular, and clinical data. Our findings suggest that persistent leukocytosis occurring at or around the time of progression to post-polycythemic myelofibrosis is associated with an overall more aggressive course of the disease.
Topics: Aged; Disease Progression; Female; Humans; Leukocytosis; Male; Middle Aged; Neutrophils; Polycythemia Vera; Primary Myelofibrosis; Prognosis
PubMed: 26336886
DOI: 10.1038/modpathol.2015.100 -
Leukemia Research Apr 2022Patients with polycythemia vera (PV) and essential thrombocythemia (ET) have increased thrombotic risk. This retrospective, real-world analysis of Medicare patients (age...
Patients with polycythemia vera (PV) and essential thrombocythemia (ET) have increased thrombotic risk. This retrospective, real-world analysis of Medicare patients (age ≥ 65 years) newly diagnosed with high-risk PV or intermediate-/high-risk ET compared mortality risk among those with versus without thrombotic events during the study period. Patients diagnosed with PV or ET with ≥ 1 inpatient or ≥ 2 outpatient claims (January 1, 2010-December 31, 2017; index was date of first qualifying claim) were included. The study included 50,405 Medicare beneficiaries with PV and 124,569 with ET. During follow-up (median [range]: PV, 34.5 [0-97.3] months; ET, 25.5 [0-97.4] months), 14,334 patients (28.4%) with PV and 30,478 (24.5%) with ET experienced thrombotic events (most commonly ischemic stroke [PV, 46.0%; ET, 42.5%]. Mortality risk was increased for patients with versus without post-index thrombosis for both PV (adjusted hazard ratio [aHR; 95% CI], 18.6 [16.1-21.6]; P < 0.001) and ET (aHR [95% CI], 25.2 [23.1-27.5]; P < 0.001). Median survival was shorter for patients who experienced a thrombotic event ≤ 1 year post-index versus those who did not (PV, 5.1 years vs not reached; ET, 3.7 vs 6.7 years; both P < 0.001). These findings highlight the importance of thrombosis risk mitigation in PV and ET management.
Topics: Aged; Humans; Medicare; Polycythemia Vera; Retrospective Studies; Thrombocythemia, Essential; Thrombosis; United States
PubMed: 35220060
DOI: 10.1016/j.leukres.2022.106809 -
Pathology Oncology Research : POR Jan 2019
Topics: Adult; Aged; Aged, 80 and over; Cerebrovascular Disorders; Female; Follow-Up Studies; Humans; Male; Middle Aged; Polycythemia Vera; Prognosis; Retrospective Studies
PubMed: 29027624
DOI: 10.1007/s12253-017-0329-9 -
Blood Cancer Journal Oct 2018Polycythemia vera is characterized by the acquisition of the JAK2V617F mutation. Recommended treatments include hydroxyurea and interferon-alpha. Several groups have...
Polycythemia vera is characterized by the acquisition of the JAK2V617F mutation. Recommended treatments include hydroxyurea and interferon-alpha. Several groups have reported a reduction in the JAK2 mutant allele burden in interferon-treated patients, but significance of this observation is questioned. We characterized the activity of ropeginterferon alpha-2b, a novel form of interferon-alpha recently shown to be safe and efficacious in polycythemia vera. Ropeginterferon was able to inhibit the proliferation of the HEL, UKE-1, and UT-7 JAK2-mutant cell lines while sparing JAK2-wild-type UT-7 and normal CD34+ cells growth. In vitro treatment of erythroid progenitors derived from PV patients showed that ropeginterferon could considerably inhibit the growth of endogenous erythroid colonies, a hallmark of polycythemia vera. Finally, we could study in sequential samples the clonal architecture of erythroid progenitors derived from patients included in a randomized study comparing hydroxyurea to ropeginterferon. After 1 year of treatment with ropeginterferon, the ratio of JAK2-mutated to wild-type colonies grown from bone marrow progenitors was reduced by 64%, compared to 25% in patients receiving hydroxyurea. This study shows that ropeginterferon has a potent targeted activity against JAK2-mutant cells and is able to drastically reduce the proportion of malignant progenitors in patients treated with this drug.
Topics: Alleles; Amino Acid Substitution; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Gene Frequency; Genotype; Humans; Interferon alpha-2; Interferon-alpha; Janus Kinase 2; Mutation; Polycythemia Vera; Polyethylene Glycols; Recombinant Proteins
PubMed: 30287855
DOI: 10.1038/s41408-018-0133-0 -
Clinical Lymphoma, Myeloma & Leukemia Sep 2019Approximately 50% of patients with polycythemia vera (PV) have PV-related symptoms at diagnosis; these symptoms might develop or worsen with time. Symptoms have been...
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.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Blood Cell Count; Disease Management; Female; Humans; Male; Middle Aged; Polycythemia Vera; Prospective Studies; Severity of Illness Index; Symptom Assessment; Treatment Outcome; United States; Young Adult
PubMed: 31303457
DOI: 10.1016/j.clml.2019.06.001 -
American Journal of Hematology Feb 2014Polycythemia vera (PV) is currently diagnosed by the World Health Organization (WHO) criteria regarding hemoglobin (HB) levels and JAK2V617F and related mutations or by...
Polycythemia vera (PV) is currently diagnosed by the World Health Organization (WHO) criteria regarding hemoglobin (HB) levels and JAK2V617F and related mutations or by the British Committee for Standards in Haematology (BCSH) guidelines predominantly based on hematocrit (HCT) values (>52% in men and >48% in women) in JAK2 mutated patients. We examined clinical features at diagnosis and outcome in 397 mutated PV patients showing a bone marrow (BM) morphology conforming with the WHO descriptions but including also cases with a HB level <18.5 g/dL in males (range 16.0-18.4) and <16.5 g/dL in females (range 15.0-16.4). These patients were regarded as masked PV (mPV) comprising 140 (35%) cases of our cohort. A comparison with the BCSH criteria based on HCT levels revealed a decrease of mPV patients to 59 (15%). In both classification systems, mPV patients were more males, presented more frequently with higher platelet counts, and increased BM reticulin fibrosis. A worsening of overall survival was documented in mPV patients in comparison with overt PV following the WHO (P = 0.011) as well as the BCSH (P = 0.0019) criteria. Risk factors for inferior survival in mPV were age >65 years and white blood cell count >15 × 10(9) /L. Without these risk factors mPV patients had the same survival as overt PV suggesting that a fraction of patients with HB lower than that required for WHO diagnosis should still be considered as overt PV. This study has established the existence of mPV by two different classification systems based on either HB or HCT threshold values.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bone Marrow; Erythrocyte Indices; Exons; Female; Humans; Janus Kinase 2; Male; Middle Aged; Mutation; Polycythemia Vera; Risk Factors; Young Adult
PubMed: 24166817
DOI: 10.1002/ajh.23617