Overview of dyslipidemia and metabolic syndrome in myeloproliferative neoplasms.

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.

Efficacy and safety outcomes in Japanese patients with low-risk polycythemia vera treated with ropeginterferon alfa-2b.

Polycythemia vera (PV) is a Philadelphia chromosome-negative myeloproliferative neoplasm characterized by clonal erythrocytosis. A phase 2 study reported that ropeginterferon alfa-2b is a well-tolerated and effective treatment for PV in Japanese patients. This post hoc analysis of the phase 2 data further evaluated outcomes in patients at low risk of thrombosis (low-risk PV). Among 20 patients with low-risk PV, 60.0% (12/20) and 85.0% (17/20) achieved < 45% hematocrit by weeks 24 and 52, respectively. The proportion of responders with complete hematologic response (CHR) was 60.0% (12/20) at week 52, and the median time to response was 11.9 months. The mean JAK2 V617F allele burden decreased from 75.8% at baseline to 53.7% at week 52. No patient experienced thrombosis or bleeding episodes. All patients experienced treatment-emergent adverse events (TEAEs) related to ropeginterferon alfa-2b, but no grade ≥ 3 TEAEs or deaths related to ropeginterferon alfa-2b occurred, and no new safety concerns arose. This analysis indicated that ropeginterferon alfa-2b may be an effective treatment option for Japanese patients with low-risk PV.

Advancements and Future Directions in Polycythemia Vera Research: A Bibliometric Analysis.

This research provides a comprehensive bibliometric analysis of polycythemia vera (PV) research trends, encompassing data from 1969 to 2024. Utilizing advanced tools, key findings reveal a notable increase in scientific production over time, reflecting growing interest and investment in PV research. Prominent themes include genetic studies, targeted therapies, and precision medicine approaches. The analysis identifies leading authors, institutions, and countries contributing to PV research, highlighting the importance of global collaboration. The study emphasizes the need to broaden genetic investigations, explore the bone marrow microenvironment, and enhance precision medicine strategies. The implications of this research extend to clinical practice, with potential advancements in diagnostics, treatments, and patient outcomes. Ultimately, addressing these challenges and embracing emerging opportunities can propel PV research forward, fostering innovation and improving the lives of affected individuals.

Spinal extramedullary hematopoiesis mimicking an epidural tumor in a patient with high-risk polycythemia vera: illustrative case.

BACKGROUND: Here the authors present the case of a 43-year-old male with a history of T-cell lymphoma, which was treated with azacitidine plus cyclophosphamide, doxorubicin, vincristine, and prednisone and autologous hematopoietic cell transplant, and high-risk polycythemia vera (PCV) presenting with severe lower-back pain radiating to the bilateral legs with associated lower-extremity weakness and splenomegaly. OBSERVATIONS: T2-weighted magnetic resonance imaging revealed multilevel epidural lesions involving T1-10 and S1-2. Because of severe spinal canal stenosis, the patient underwent surgical decompression of T5-7, with immediate postoperative alleviation of the lower-extremity pain and complete resolution of the lower-leg weakness. Biopsy results revealed extramedullary hematopoiesis (EMH) mimicking a spinal epidural tumor. EMH is radiosensitive and displays a rapid response to low dosages, so the patient was further treated with palliative radiation therapy for residual tumors and symptom alleviation, as well as hydroxyurea and corticosteroids as indicated for cytoreduction. LESSONS: EMH associated with PCV or myeloproliferative conditions occurring within the spine is a rare phenomenon without a standard treatment approach. https://thejns.org/doi/10.3171/CASE23659.

Relationship between amide ratio assessed by Fourier-transform infrared spectroscopy: A biomarker candidate for polycythemia vera disease.

The study utilized Fourier transform infrared (FTIR) spectroscopy coupled with chemometrics to investigate protein composition and structural changes in the blood serum of patients with polycythemia vera (PV). Principal component analysis (PCA) revealed distinct biochemical properties, highlighting elevated absorbance of phospholipids, amides, and lipids in PV patients compared to healthy controls. Ratios of amide I/amide II and amide I/amide III indicated alterations in protein structures. Support vector machine analysis and receiver operating characteristic curves identified amide I as a crucial predictor of PV, achieving 100% accuracy, sensitivity, and specificity, while amide III showed a lower predictive value (70%). PCA analysis demonstrated effective differentiation between PV patients and controls, with key wavenumbers including amide II, amide I, and CH lipid vibrations. These findings underscore the potential of FTIR spectroscopy for diagnosing and monitoring PV.

Clinical and Economic Implications of Hydroxyurea Intolerance in Polycythemia Vera in Routine Clinical Practice.

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.

Translation, Cultural Adaptation, and Validation into Romanian of the Myeloproliferative Neoplasm Symptom Assessment Form-Total Symptom Score (MPN-SAF TSS or MPN-10) Questionnaire.

Background: Patients with myeloproliferative neoplasms (MPNs) experience a high disease-related symptom burden. A specific instrument to evaluate quality of life (QoL), i.e., the MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS; MPN-10), was developed. We conducted the translation, cultural adaptation, and validation into Romanian of the MPN-10. Methods: We translated the MPN-10 and tested its psychometric properties. Results: We recruited 180 MPN patients: 66 polycythemia vera (36.67%), 61 essential thrombocythemia (33.89%), 51 primary and secondary myelofibrosis (SMF) (28.33%), and 2 MPN-unclassifiable (1.11%). The mean TSS was 19.51 ± 16.51 points. Fatigue, inactivity, and concentration problems were the most cumbersome symptoms. We detected scoring differences between MPN subtypes regarding weight loss (p < 0.001), fatigue (p = 0.006), early satiety (p = 0.007), night sweats (p = 0.047), pruritus (p = 0.05), and TSS (p = 0.021). There were strong positive associations between TSS and inactivity, fatigue, and concentration problems, and moderate negative correlations between QoL scores and all MPN-10 items. Cronbach's α internal consistency coefficient was 0.855. The Kaiser-Meyer-Olkin construct validity test result was 0.870 and the Bartlett Sphericity Test was significant (p < 0.001). Symptom scores were loaded into one single factor according to the exploratory factor analysis. Conclusions: The Romanian MPN-10 version displayed excellent psychometric properties and is a reliable instrument for assessing symptom burden and QoL in Romanian MPN patients.

Disseminated cerebral cryptococcosis after silent West Nile virus infection in a patient with polycythemia vera: A case report and review of the literature.

Although disseminated cryptococcosis can occur occasionally, it is most commonly seen in immunodeficient patients. In 2005, a 43-year-old man was diagnosed with polycythemia vera. Following in 2018, he experienced an unknown-cause fever and headache. To establish the source of the symptoms, a magnetic resonance imaging scan of the brain was performed, which indicated meningeal and gyral-leptomeningeal thickening and several localized T2 hyperintense lesions measuring up to 10 × 14 mm in diameter. Cryptococcus neoformans was then cultivated from cerebrospinal fluid. Serum IgM antibodies against West Nile Virus were positive. After 8 weeks of treatment with amphotericin B and fluconazole, the overall condition improved, and the cerebrospinal fluid control culture became negative. The symptoms returned shortly after discontinuing antifungal therapy, necessitating the reintroduction of fluconazole. Currently, the patient is stable and responding positively to ruxolitinib. Here, it is demonstrated how a patient with polycythemia vera due to immunological weakness might develop disseminated cryptococcosis of the brain after West Nile virus infection.

[Recent findings and advances in treatment of myeloproliferative neoplasms].

Many novel agents have been developed for BCR::ABL1-negaive myeloproliferative neoplasms (MPN), namely, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Some of these agents not only achieve hematologic complete response, reduce spleen size, and alleviate constitutional symptoms, but also induce molecular response, which means that they reduce the allele burden of driver gene mutations. These agents also prevent and alleviate fibrosis in bone marrow, which reduces the incidence of thrombotic events and disease progression and might improve prognosis. This article discusses the latest findings and promising treatments, including ongoing clinical trials, in PV, ET, and PMF.

Polycythemia vera: past, present and future.

There has been remarkable progress in the development of novel therapeutic approaches for patients with polycythemia vera (PV). Historically, therapy goals in PV were to mitigate thrombotic risks and control blood counts and symptoms. There is now increased focus on disease modification through progressive attrition of JAK2-mutant stem/progenitor cells. The approval of ropeginterferon, a novel monoPEGylated interferon, coupled with findings from LOW-PV and longer-term data from CONTINUATION-PV that strongly support a disease-modifying effect for interferon therapy, have transformed the treatment paradigm for this disorder. Results from MAJIC-PV demonstrate that disease modification can also be induced with JAK inhibitors, suggesting an urgent need to incorporate prospective molecular monitoring into PV trials. Novel agents, such as hepcidin mimetics, aim to help patients with PV restore normal hematocrit levels and become phlebotomy-free. In this review, we will summarize past, current and future approaches to PV management and highlight findings from key clinical studies.

Real-life use of ropeg-interferon α2b in polycythemia vera: patient selection and clinical outcomes.

Ropeginterferon-alfa2b (ropegIFNα2b) is a long-acting IFN formulation with broad FDA/EMA approval as a therapy of polycythemia vera (PV) with no symptomatic splenomegaly. There is currently lack of information on the real-world patient selection, including the impact of local reimbursement policies, and drug management, particularly: type/timing of screening and follow-up tests; absolute/relative contraindications to therapy; ropegIFNα2b dose and combinations with hydroxyurea. As a sub-analysis of the PV-ARC retrospective study (NCT06134102), we here report our monocenter experience with ropegIFNα2b in the period from January 2021, corresponding to drug availability outside clinical trial, and December 2023. Among the 149 patients with EMA/FDA indication, only 55 (36.9%) met the local reimbursement criteria and 18 (12.1%) received ropegIFNα2b. Thanks to appropriate screening, relative/absolute contraindications to ropegIFNα2b were detected and managed in a multidisciplinary manner. Efficacy and safety of ropegIFNα2b was confirmed, with 3 cases of early molecular response. General use of low ropegIFNα2b dose, with frequent need for hydroxyurea combinations, was noted. This real-world experience suggests a significant impact of local regulations on drug prescription and the need for greater real-world data collection on ropegIFNα2b in PV patients. Also, it describes appropriate multidisciplinary screening and monitoring procedures during ropegIFNα2b therapy.

Advances in Molecular Understanding of Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis: Towards Precision Medicine.

Myeloproliferative neoplasms (MPNs), including Polycythemia Vera (PV), Essential Thrombocythemia (ET), and Primary Myelofibrosis (PMF), are characterized by the clonal proliferation of hematopoietic stem cells leading to an overproduction of hematopoietic cells. The last two decades have seen significant advances in our understanding of the molecular pathogenesis of these diseases, with the discovery of key mutations in the JAK2, CALR, and MPL genes being pivotal. This review provides a comprehensive update on the molecular landscape of PV, ET, and PMF, highlighting the diagnostic, prognostic, and therapeutic implications of these genetic findings. We delve into the challenges of diagnosing and treating patients with prognostic mutations, clonal evolution, and the impact of emerging technologies like next-generation sequencing and single-cell genomics on the field. The future of MPN management lies in leveraging these molecular insights to develop personalized treatment strategies, aiming for precision medicine that optimizes outcomes for patients. This article synthesizes current knowledge on molecular diagnostics in MPNs, underscoring the critical role of genetic profiling in enhancing patient care and pointing towards future research directions that promise to further refine our approach to these complex disorders.

The Systemic Inflammation Index: A New Candidate Minor Criterion in the Diagnosis of Polycythemia Vera.

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.

[Unusual progression of polycythemia vera]. / Ungewöhnliche Progression einer Polycythaemia vera.

The case of a male patient with newly diagnosed polycythemia vera showing rare and unusually rapid progression with phenotypic change towards chronic myelomonocytic leukemia is presented. The case report illustrates remarkably rapid disease progression including a structural change in usually indolent polycythemia vera and highlights the prognostic relevance of enhanced molecular genetic testing.

Noninfectious Ascites Neutrophilia in a Patient With Polycythemia Vera.

A 59-year-old woman with polycythemia vera-related portal hypertension requiring frequent paracentesis was admitted for asymptomatic recurrent spontaneous bacterial peritonitis, which was diagnosed based on elevated polymorphonuclear (PMN) count. She had multiple similar admissions during which she was treated with antibiotics. The patient had chronic baseline leukocytosis due to polycythemia vera. Repeat paracentesis after intravenous antibiotics demonstrated persistent elevation of PMN count without clinical symptoms. A multidisciplinary team concluded that the increased PMN count was secondary to polycythemia. The patient was diagnosed with omental extramedullary hematopoiesis, a rare condition causing elevated PMN count in the absence of bacterial contamination.

Histopathological Confirmed Polycythemia Vera with Transformation to Myelofibrosis Depicted on [18F]FDG PET/CT.

We present a case of a 59-year-old male diagnosed with polycythemia vera (PV) for many years, who presented with a relatively abrupt onset of heavy constitutional symptoms, including fatigue, night sweats, and a 10% weight loss over 6 weeks. Despite the known initial diagnosis of PV, the presence of profound B-symptoms prompted further investigation. A positron emission tomography/computed tomography (PET/CT) scan with 18F-Fluorodeoxyglucose ([18F]FDG) was performed to exclude malignant diseases. The [18F]FDG PET/CT revealed intense metabolic activity in the bone marrow of the proximal extremities and trunk skeleton, as well as a massively enlarged spleen with increased metabolic activity. Histopathologically, a transformation to myelofibrosis was revealed on a bone marrow biopsy. The case intends to serve as an exemplification for [18F]FDG PET/CT in PV with transformation to myelofibrosis (post-PV myelofibrosis).

Myocardial infarction in young individual: A case report of polycythemia vera-induced acute inferior wall myocardial infarction.

Acute coronary syndrome is commonly associated with traditional cardiovascular risk factors such as smoking, hypertension, diabetes, and hyperlipidemia. Myocardial infarction in a young person presents a significant challenge because its etiology is least likely associated with atherosclerosis. Polycythemia vera refers to one of the rare causes of myocardial infarction, which involves enhanced erythrocyte levels, leukocytosis, thrombocytosis, splenomegaly, and a greater chance of vascular occlusion due to clotting in coronary arteries. A 22-year-old male from Pakistan, Asia without typical risk factors, presented with severe chest pain. Electrocardiography indicated acute inferior wall myocardial infarction, and streptokinase was administered. Subsequent investigations confirmed polycythemia vera. Treatment with hydroxyurea and aspirin was initiated, whereas normal coronary arteries in CT coronary angiogram were observed. This case highlights polycythemia vera's rare role in young individuals' heart attacks without known risk factors, emphasizing the need for early detection and specialized treatments involving hematologists to prevent future thrombotic episodes.

Hematocrit control and thrombotic risk in patients with polycythemia vera treated with ruxolitinib in clinical practice.

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by unregulated red blood cell production resulting in elevated hemoglobin and/or hematocrit levels. Patients often have symptoms such as fatigue, pruritus, and painful splenomegaly, but are also at risk of thrombosis, both venous and arterial. Ruxolitinib, a selective Janus kinase inhibitor, is approved by the US Food and Drug Administration as second-line cytoreductive treatment after intolerance or inadequate response to hydroxyurea. Although ruxolitinib has been widely used in this setting, limited data exist in the literature on ruxolitinib treatment patterns and outcomes among patients with PV in routine clinical practice. We report a retrospective, observational, cohort study of patients treated for PV with ruxolitinib across three US centers (academic and regional practice) from December 2014-December 2019. The study included 69 patients, with a median follow-up duration of 3.7 years (95% CI, 2.9-4.4). Our data demonstrate very high rates of hematocrit control (88% of patients by three months and 89% by six months); few patients required dose adjustments or suspension. No arterial thromboses were observed; however, the follow-up duration does not allow for the generation of meaningful conclusions from this. Three patients had thrombotic events; one was in the setting of a second malignancy, one post-operative, and a third related to prolonged immobility. We also found that 28% of patients initiated ruxolitinib as a result of poorly controlled platelet counts, second only to hydroxyurea intolerance (46%) as a reason to start therapy. In clinical practice, ruxolitinib continues to be effective in controlling hematocrit levels after three and six months of treatment in patients and is associated with low thrombotic risk.

Treatment outcome and germline predictive factors of ropeginterferon alpha-2b in myeloproliferative neoplasm patients.

BACKGROUND: Studies have shown that some single nucleotide polymorphisms (SNPs) could serve as excellent markers in foretelling the treatment outcome of interferon (IFN) in myeloproliferative neoplasms (MPN). However, most work originated from western countries, and data from different ethnic populations have been lacking. METHODS: To gain insights, targeted sequencing was performed to detect myeloid-associated mutations and SNPs in eight loci across three genes (IFNL4, IFN-γ, and inosine triphosphate pyrophosphatase [ITPA]) to explore their predictive roles in our cohort of 21 ropeginterferon alpha-2b (ROPEG)-treated MPN patients, among whom real-time quantitative PCR was also performed periodically to monitor the JAK2V617F allele burden in 19 JAK2V617F-mutated cases. RESULTS: ELN response criteria were adopted to designate patients as good responders if they achieved complete hematological responses (CHR) within 1 year (CHR1) or attained major molecular responses (MMR), which occurred in 70% and 45% of the patients, respectively. IFNL4 and IFN-γ gene SNPs were infrequent in our population and were thus excluded from further analysis. Two ITPA SNPs rs6051702 A>C and rs1127354 C>A were associated with an inferior CHR1 rate and MMR rate, respectively. The former seemed to be linked to grade 2 or worse hepatotoxicity as well, although the comparison was of borderline significance only (50%, vs. 6.7% in those with common haplotype, p = 0.053). Twelve patients harbored 19 additional somatic mutations in 12 genes, but the trajectory of these mutations varied considerably and was not predictive of any response. CONCLUSIONS: Overall, this study provided valuable information on the ethnics- and genetics-based algorithm in the treatment of MPN.