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2016 World Health Organization diagnostic criteria for polycythemia vera and essential thrombocythemia
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The new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues was published in September 2017. Under the category of myeloproliferative neoplasms (MPNs), the revised document includes seven subcategories: chronic myeloid leukemia, chronic neutrophilic leukemia, polycythemia ve...
Context in source publication
Context 1
... combination of clinical, morphological, and mole- cular genetic features is thought by the WHO as the most suitable attempt to define disease entities such as MPNs (Tables 1 and 2) 1,2,12 . Following the updated 2008 WHO classification 12 , a number of clinical-pathological studies conducted by different groups have validated these diag- nostic guidelines including the importance of morpholo- gical features [13][14][15][16][17][18][19][20][21][22] . ...
Similar publications
Background
Chronic neutrophilic leukemia (CNL) is an extremely rare myeloproliferative neoplasm (MPN). Due to the difficulty in its diagnosis, the diagnostic criterion was just recently revised in 2016. CNL is defined as: A clonal disorder with sustained primary neutrophilia, with normal neutrophil maturation, that does not meet other MPN criteria,...
Citations
... This results in the manifestation of a heterogeneous group of disorders. The initial term "myeloproliferative disorders," originally introduced by William Dameshek in 1951, has been formally standardized and rephrased as "myeloproliferative neoplasms" by the World Health Organization in 2016 [2]. ...
... Notably, it is imperative to highlight that mastocytosis no longer falls under the MPN category. This revised categorization represents a pivotal advance in the field, indicating a comprehensive and rigorous approach to classifying these complex disorders [2,3]. ...
Myeloproliferative neoplasms (MPNs) occur due to the abnormal proliferation of one or more terminal myeloid cell lines in peripheral blood. Subjects suffering from MPNs display a high burden of cardiovascular risk factors, and thrombotic events are often the cause of death in this population of patients. Herein, we provide a brief overview of dyslipidemia and metabolic syndrome and their epidemiology in MPNs and examine the common molecular mechanisms between dyslipidemia, metabolic syndrome, and MPNs, with a special focus on cardiovascular risk, atherosclerosis, and thrombotic events. Furthermore, we investigate the impact of dyslipidemia and metabolic syndrome on the occurrence and survival of thrombosis in MPN patients, as well as the management of dyslipidemia in MPNs, and the impact of MPN treatment on serum lipid concentrations, particularly as side/adverse effects reported in the context of clinical trials.
... Among those tested for the JAK2 617F mutation, 91.6% were positive. This is a little lower than the WHO guideline-referenced percentage of 95% [18], but higher than that reported in other published studies [19]. It is possible that some of the patients with PV diagnosis in their MHS EMR who did not have a documented JAK2 mutation test status in their MHS EMR were actually tested for JAK2 at a hospital and found positive, as part of their overall diagnosis procedure, e.g., prior to the availability of this test in MHS. ...
Background/Objectives: Polycythemia vera (PV) is a chronic hematologic neoplasm commonly treated with hydroxyurea (HU). We utilized the advanced digitalized database of Maccabi Healthcare Services to retrospectively investigate the clinical and economic implications of HU intolerance in the routine clinical care of PV patients in Israel. Methods: We collected data on demographics, physician visits, hospitalizations, laboratory results, medication purchases, cardiovascular and thrombotic events, mental health, economic outcomes, and mortality. Outcomes included cardiovascular and other thrombotic events, disease progression, mental health events, economic outcomes, and overall mortality. Results: Of the 830 patients studied, 3 (0.4%) were resistant to HU treatment, 318 (38.3%) were intolerant to HU treatment, and 509 (61.3%) were stable on HU treatment. The venous thrombosis rate was significantly higher among HU-intolerant compared to HU-stable patients (1.58 vs. 0.47 per 100 person-years [PY], respectively; p < 0.001). The rate of progression to myelofibrosis was 6 vs. 0.9 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively (p < 0.001), and the rate of progression to acute myeloid leukemia (AML) was 1.16 vs. 0.2 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively (p < 0.001). The phlebotomy requirement, mortality rate, and total hospitalization days among HU-intolerant patients were significantly higher than in HU-stable patients (p = 0.049, p < 0.001, p < 0.001, respectively). More mental health-related events were noted in HU-intolerant patients vs. HU-stable patients (p = 0.007), and the total healthcare cost ratio was 2.65 for the HU-intolerant patients compared with HU-stable patients. Conclusions: This study suggests that HU-intolerant patients are more likely to have worse outcomes than HU-stable patients, highlighting the need for the close monitoring of these patients for disease-related complications or progression.
... Since quality-controlled spirometry results were obtained at the 2nd follow-up, we included 7,515 participants from the 2nd follow-up in our study as the initial analysis point. The following participants were excluded: (1) those without initial spirometry data in the 2nd follow-up; (2) those without follow-up spirometry data at least once during the 3rd − 6th follow-up; (3) those without Hb data in the 2nd follow-up; (4) those with chronic lung disease (FEV 1 /FVC < 70% [forced vital capacity (FVC), forced expiratory volume in 1 s (FEV 1 )] or current inhaler use); (5) those who met anemia [19] or erythrocytosis criteria [20] of the World Health Organization (WHO); (6) those without smoking data in the 2nd follow-up. ...
... We excluded patients with anemia or erythrocytosis at baseline to examine the effect of Hb levels on lung function in a healthy population. According to the WHO diagnostic criteria, anemia is de ned as Hb concentrations < 13 g/dL in men and < 12 g/dL in women, whereas erythrocytosis is de ned as Hb concentrations > 18.5 g/dL in men and > 16.5 g/dL in women [19,20]. ...
... We evaluated the longitudinal associations between lung function and Hb levels using multiple linear mixed regression analyses. Because the baseline characteristics and de nitions of erythrocytosis and anemia differ by gender [19,20], we analyzed men and women separately. Age, gender, height, smoking history, area of residence, and menopausal status were adjusted. ...
Background
Evidence regarding the long-term association between hemoglobin (Hb) level and lung function in healthy individuals is scarce. This study aimed to determine the longitudinal association between Hb level and lung function in a community-based population cohort in South Korea.
Methods
We used linear mixed regression analysis to evaluate the longitudinal associations between Hb levels and lung function parameters, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC. Additionally, we used a generalized estimating equation to calculate the odds ratio (OR) of chronic obstructive pulmonary disease (COPD) according to Hb level.
Results
Over an 8-year biennial follow-up of 4,468 patients (median age, 53.9 years; men, 49.0%), we observed that in men, Hb levels were positively associated with lung function (estimated values of FVC: 16.7 mL, FEV1: 15.5 mL, FEV1/FVC: 0.18%; all P < 0.001) and a decreased incidence of COPD (OR = 0.83, P < 0.001). In women, Hb levels were positively associated with FVC but not with FEV1 or FEV1/FVC (estimated values of FVC: 4.7 mL, P = 0.045; FEV1: 3.1 mL, P = 0.142; FEV1/FVC: 0.01%, P = 0.838). The incidence of COPD was not significantly different among women (OR = 0.93, P = 0.568). In postmenopausal women, higher Hb levels were associated with increased lung function (estimated values of FVC: 11.8 mL, P < 0.001; FEV1: 9.8 mL, P < 0.001; FEV1/FVC: 0.09%, P = 0.052), but the incidence of COPD was not statistically significant (OR = 0.93, P = 0.568).
Conclusions
A decreased Hb level was associated with reduced lung function and an increased incidence of COPD in men.
... Clinical data of 74 patients, who were diagnosed with ET, PV, and PMF according to 2016 WHO criteria [11,21] between September 2020 and July 2023, were Content courtesy of Springer Nature, terms of use apply. Rights reserved. ...
Predicting the likelihood vascular events in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN) is essential for the treatment of the disease. However, effective assessment methods are lacking. Thrombin-antithrombin complex (TAT), plasmin-α2- plasmininhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) are the new direct indicators for coagulation and fibrinolysis. The aim of this study was to investigate the changes of these four new indicators in thrombotic and hemorrhagic events in BCR/ABL1-negative MPN. The study cohort of 74 patients with BCR/ABL negative myeloproliferative disorders included essential thrombocythemia, polycythemia vera, and primary myelofibrosis (PMF). A panel of 4 biomarkers, including TAT, PIC, TM, and t-PAIC were determined using Sysmex HISCL5000 automated analyzers, whereas fibrin/fibrinogen degradation products (FDP), D-dimer and Antithrombin III (ATIII) were analyzed using Sysmex CS5100 coagulation analyzer. A total of 24 (32.4%) patients experienced thrombotic events and hemorrhagic events occurred in 8 patients (10.8%). Compared to patients without hemorrhagic-thrombotic events, patients with thrombotic events had higher fibrinogen (FIB) level, FDP level and lower ATIII activity, while patients with hemorrhagic events had lower white blood cell count and hemoglobin level, higher FDP level (P < 0.05). Patients with a JAK2V617F mutation were more likely to experience thrombotic events (P < 0.05). In addtion, patients with thrombotic events had higher TAT, PIC, TM, and t-PAIC levels than patients without hemorrhagic-thrombotic events (P < 0.05), whereas patients with hemorrhagic events had a lower median value in TAT and TM (no statistical difference, P > 0.05). Patients with higher TAT, TM and t-PAIC were more likely to experience thrombotic events (P < 0.05), and only TAT was positively correlated with thrombotic events (Spearman r =0.287, P = 0.019). TAT, PIC, TM, and t-PAIC combined with ATIII and FDP have a certain value for predicting thrombosis in patients with BCR/ABL1-negative MPN. These 6 parameters are worth further exploration as predictive factors and prognostic markers for early thrombotic events.
... PV is classified as a clonal myeloproliferative neoplasm (MPN) and is a well-recognized disorder of hematopoietic stem cells [3]. In 2016, the World Health Organization (WHO) revised the diagnostic criteria for PV, which has considerably altered the diagnostic approach [4]. Although these criteria were revised in 2022, no changes were made except that the determination of an increased red cell mass with Cr-labeled red cells has been removed as a diagnostic criterion [5]. ...
... Patients who underwent further examinations due to the detection of polycythemia at our hospital from January 2020 to December 2023 and were then diagnosed with either PV or SP were included in this study. The laboratory thresholds used to diagnose polycythemia were determined according to the 2016 WHO criteria (hemoglobin > 16.5 mg/L for men and >16.0 mg/L for women and/or hematocrit > 49% for men and >48% for women) [4]. Patients with signs of active infection at the time of diagnosis, those with concomitant malignancy and/or autoimmune disease, individuals who had receiving steroids and/or immunosuppressants and/or immunomodulator medication, and subjects with missing data regarding the criteria required for the diagnosis of PV or SP were excluded from the study. ...
... All the data for patients, including the polycythemia diagnosis and related features, demographic characteristics, smoking status, laboratory findings and other clinical and laboratory data were collected retrospectively from the hospital database. The diagnosis of PV was made according to the 2016 WHO criteria [4]. Patients with polycythemia who did not meet these criteria were classified as having SP. ...
Aim: To investigate inflammation indices and erythropoietin levels for their potential role in distinguishing polycythemia vera from secondary polycythemia and to compare different parameter combinations in terms of the diagnostic accuracy. Methods: This retrospective cohort was created from patients assessed for polycythemia from January 2020 to December 2023. Polycythemia vera diagnosis was made according to the 2016 World Health Organization criteria (n = 145). Those who did not fulfill the criteria were defined as having secondary polycythemia (n = 84). Results: The neutrophil lymphocyte ratio, platelet lymphocyte ratio and systemic immune-inflammation index were significantly higher in the polycythemia vera group (p < 0.001 for all). Erythropoietin had the highest area under the curve in the analysis to distinguish groups, followed by the systemic immune-inflammation index. The platelet lymphocyte ratio (≥135) had the highest specificity to detect polycythemia vera, followed closely by the systemic immune-inflammation index. The sensitivity for polycythemia vera detection was highest with the erythropoietin and systemic immune-inflammation index combination, followed by erythropoietin and the neutrophil lymphocyte ratio. All the single and combinatory variables exhibited significant performance in predicting polycythemia vera after adjusting for age and sex. However, the erythropoietin and systemic immune-inflammation index combination had the highest odds ratio, followed by erythropoietin alone. Conclusion: These are promising findings supporting the usability of these biomarkers, especially the systemic immune-inflammation index, as minor criteria in the diagnosis of polycythemia vera. It is especially crucial to note that using erythropoietin in combination with these markers may improve diagnostic accuracy.
... To the best of our knowledge, the current study is the first to systematically evaluate utility of ANC, ALC, platelet count and their ratios, NLR and PLR, for thrombotic risk stratification in patients with prefibrotic and overt fibrotic MF. Current data, as well as previous reports [3,4,8], confirm the high thrombotic risk associated with the MPN phenotype of MF, which seems to be more pronounced in overt fibrotic MF patients. Thrombosis imposes a substantial morbidity burden on MF patients [42,43] and mandates the introduction of specific therapies that may further make it difficult to optimize care [44]. ...
Aim: To investigate the prognostic contribution of absolute neutrophil (ANC), lymphocyte (ALC), platelet count and their ratios, neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR), to thrombotic risk in patients with prefibrotic and overt fibrotic myelofibrosis (MF). Methods: We retrospectively analyzed a cohort of 256 patients with prefibrotic (85 patients) and overt fibrotic MF (171 patients) treated in six Croatian hematological centers. Results: Prefibrotic compared to overt fibrotic MF patients presented with significantly higher ALC, platelet count and PLR, and experienced longer time to thrombosis (TTT). Among prefibrotic patients, ANC > 8.33 × 109/L (HR 13.08, p = 0.036), ALC > 2.58 × 109/L (HR 20.63, p = 0.049) and platelet count > 752 × 109/L (HR 10.5, p = 0.043) remained independently associated with shorter TTT. Among overt fibrotic patients, ANC > 8.8 × 109/L (HR 4.49, p = 0.004), ALC ≤ 1.43 × 109/L (HR 4.15, p = 0.003), platelet count ≤ 385 × 109/L (HR 4.68, p = 0.004) and chronic kidney disease (HR 9.07, p < 0.001) remained independently associated with shorter TTT. Conclusions: Prognostic properties of ANC, ALC and platelet count are mutually independent and exceed those of NLR and PLR regarding thrombotic risk stratification. ALC and platelet count associate in opposite directions with thrombotic risk in prefibrotic and overt fibrotic MF patients.
... The reported incidence of MPN-U has been variable, comprising less than 5% to greater than 20% of all MPNs depending on the stringency of the application of diagnostic criteria, potential differences in population with a bias toward early-phase disease, incomplete data availability, or biopsy performed following cytoreductive therapy. 6,7 Changes to the diagnostic criteria for MPNs in the 2016 revised fourth edition WHO monograph 2 increased the ability to place MPN-U into more specific MPN categories. 3,8,9 However, even with strict adherence to revised diagnostic criteria, a subset of MPNs cannot be further subclassified into more specific variants, estimated as less than 5% of MPNs. ...
... 3,8,9 However, even with strict adherence to revised diagnostic criteria, a subset of MPNs cannot be further subclassified into more specific variants, estimated as less than 5% of MPNs. 3,7 These misfit cases result in MPN-U showing a range of clinicopathologic presentations and differences in prognosis depending on the stage of disease. Creating further challenges, MPN-U cases remain relatively understudied. ...
Objectives
Myeloproliferative neoplasm, unclassifiable (MPN-U, revised to MPN, not otherwise specified in the fifth edition of the World Health Organization classification) is a heterogeneous category of primary marrow disorders with clinical, morphologic, and/or molecular features that preclude classification as a more specific MPN subtype due to stage at diagnosis, overlapping features between MPN subtypes, or the presence of coexisting disorders. Compared with other MPN subtypes, the contribution of the mutational landscape in MPN-U in conjunction with other clinical and morphologic biomarkers to prognosis has been less well investigated.
Methods
We performed a multicenter, retrospective study of MPN-U (94 cases) to better define the clinicopathologic features, genetic landscape, and clinical outcomes, including subgroups of early-stage, advanced-stage, and coexisting disorders. The Dynamic International Prognostic Scoring System (DIPSS) plus scoring system was applied to assess its relevance to MPN-U prognosis.
Results
Multivariate analysis demonstrated bone marrow blast count and DIPSS plus score as statistically significant in predicting overall survival. Univariate analysis identified additional potential poor prognostic markers, including abnormal karyotype and absence of JAK2 mutation. Secondary mutations were frequent in the subset analyzed by next-generation sequencing (26/37 cases, 70.3%) with a borderline association between high molecular risk mutations and overall survival.
Conclusions
This study, as one of the largest of MPN-U studies incorporating both clinicopathologic and molecular data, moves toward identification of biomarkers that better predict prognosis in this heterogeneous category.
... Most patients suffering from PV carry the driver Janus kinase 2 gene (JAK) mutation JAK2 V617F . PV is associated with an over-production of blood cells, increased incidence of thromboembolic and hemorrhagic complications, and long-term risk of transformation to myelofibrosis (MF) or acute myeloid leukemia (AML) [1][2][3]. Patients suffering from PV have lower rates of survival and the incidence rate of thrombotic, fibrotic, or leukemic events, which are the main causes of morbidity and mortality, at 20 years is 26%, 16%, and 4%, respectively [4,5]. Age and history of thrombotic events (TEs) were the factors included in the conventional risk model to determine the risk of thrombosis. ...
Background
Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation.
Methods
Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2V617F allelic burden, time to first CHR, and safety assessments.
Results
The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm² at baseline to 50.2 cm² at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed.
Conclusion
The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.
... PV is classified as a clonal myeloproliferative neoplasm (MPN) and is a well-recognized disorder of hematopoietic stem cells [3]. In 2016, the World Health Organization (WHO) revised the diagnostic criteria for PV, which has considerably altered the diagnostic approach [4]. PV can cause significant cardiovascular morbidities and mortality [5]. ...
... Patients who underwent further examinations due to detection of polycythemia at our hospital from January 2020 to December 2023 and were then diagnosed with either PV or SP were included in this study. Laboratory thresholds used to diagnose polycythemia were determined according to the 2016 WHO criteria (hemoglobin >16.5 mg/L for men and >16.0 mg/L for women and/or hematocrit >49% for men and >48% for women) [4]. Patients with signs of active infection at the time of diagnosis, those with concomitant malignancy and/or autoimmune disease, individuals who had receiving steroids and/or immunosuppressants and/or immunomodulator medication, and subjects with missing data regarding the criteria required for the diagnosis of PV or SP were excluded from the study. ...
... All data for patients, including polycythemia diagnosis and related features, demographic characteristics, smoking status, laboratory findings and other clinical and laboratory data were collected retrospectively from the hospital database. The diagnosis of PV was made according to 2016 WHO criteria [4]. Patients with polycythemia who did not meet these criteria were classified as having SP. ...
Aim: To investigate inflammation indices and erythropoietin (EPO) levels for their potential role in distinguishing polycythemia vera (PV) from secondary polycythemia (SP), and to compare different parameter combinations in terms of diagnostic accuracy. Methods: This retrospective cohort was created from patients assessed for polycythemia from January 2020 to December 2023. PV diagnosis was made according to the 2016 WHO criteria (n=145). Those who did not fulfill the criteria were defined as having SP (n=84). Results: NLR, PLR and SII were significantly higher in the PV group (p
... Within these populations, we calculated changes from baseline to week 8 and EOT, and their 95% confidence intervals. For analyses of PLT, the upper normal range of PLT was defined as 35.2 × 10 4 /µL (the 97.5% upper reference limit in healthy adult in Japan) [25] and 45.0 × 10 4 /μL (the WHO definition of thrombocytosis) [26]. All statistical analyses were conducted using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA), and all adverse events were categorized using standardized terminology by MedDRA version 21.0. ...
Background
Iron deficiency anemia (IDA) increases levels of C-terminal fibroblast growth factor 23 (cFGF23) and platelet count (PLT), each of which is associated with cardiovascular events. Therefore, we hypothesized that iron replacement with ferric citrate hydrate (FC) would decrease cFGF23 levels and PLT in patients with IDA.
Methods
In a randomized, open-label, multicenter, 24-week clinical trial, patients with non-dialysis-dependent chronic kidney disease (CKD) and non-CKD complicated by IDA (8.0 ≤ hemoglobin < 11.0 g/dL; and serum ferritin < 50 ng/mL [CKD]; < 12 ng/mL [non-CKD]) were randomized 1:1 to FC-low (500 mg: approximately 120 mg elemental iron/day) or FC-high (1000 mg: approximately 240 mg elemental iron/day). If sufficient iron replacement had been achieved after week 8, further treatment was discontinued.
Results
Seventy-three patients were allocated to FC-low (CKD n = 21, non-CKD n = 15) and FC-high (CKD n = 21, non-CKD n = 16). Regardless of CKD status, FC increased serum ferritin and transferrin saturation, did not change intact FGF23 or serum phosphorus, but decreased cFGF23. In FC-low group, median changes in cFGF23 from baseline to week 8 were −58.00 RU/mL in CKD and −725.00 RU/mL in non-CKD; in FC-high group, the median changes were −66.00 RU/mL in CKD and −649.50 RU/mL in non-CKD. By week 8, FC treatment normalized PLT in all patients with high PLT at baseline (>35.2 × 10 ⁴ /µL; FC-low: 1 CKD, 8 non-CKD; FC-high: 3 CKD, 8 non-CKD).
Conclusion
Regardless of CKD status, iron replacement with FC decreased elevated cFGF23 levels and normalized elevated PLT in patients with IDA.
Clinical trial registration number
jRCT2080223943.
