The Swedish nationwide study by Leontyeva et al. (Haematologica, sept, 2025) revealed that patients with myeloproliferative neoplasms (MPN) continue to lose life years compared with the general population, with polycythemia vera (PV) showing a 1.8-year loss in restricted mean survival at 15 years. Despite being classified as "low risk," these younger patients lose more life years relative to agematched peers. They face decades of exposure to clonal proliferation, inflammation, and thromboinflammation, which contribute to vascular injury, myelofibrosis, and secondary cancers. Evidence suggests that early, biology-guided therapy may modify this trajectory. Interferon, particularly ropeginterferon alfa-2b, and ruxolitinib reduces JAK2V617F allele burden, systemic inflammation, as reflected by the neutrophil-to-lymphocyte ratio (NLR), and thrombosis rates, demonstrating long-term disease-modifying potential. The challenge lies in identifying which younger patients should receive cytoreductive therapy, as these treatments, while effective, may be poorly tolerated or burdensome over decades. Biological markers such as persistent leukocytosis, elevated NLR, rising JAK2V617F variant allele frequency, or high phlebotomy burden can guide treatment decisions more precisely than age alone. Tailoring therapy in younger PV patients according to disease biology and individual tolerance may prevent irreversible complications, improve quality of life, and ultimately reduce the years of life lost.

Introduction: Therapeutic phlebotomy involves the controlled removal of blood from a patient to reduce complications in polycythemia, in which 300 to 400 mL of blood is removed. Polycythaemia is a condition characterised by an increase in red cell mass and is commonly seen secondary to smoking, Chronic Obstructive Pulmonary Disease (COPD), congenital heart disease and polycythaemia vera. Patients with polycythaemia have an increased risk of thrombotic events such as stroke, coronary artery disease and deep vein thrombosis compared with normal individuals. Aim: To evaluate the effect of therapeutic phlebotomy on haematologic parameters in cases of polycythemia. Materials and Methods: This was a retrospective, crosssectional study conducted in the Department of Transfusion Medicine, ESIC Medical College and PGIMSR, Bengaluru, Karnataka, India,, for a period of one year from January 2024 to December 2024. A total of 186 therapeutic phlebotomy procedures were recorded for polycythemia, involving 104 patients during the study period who were included in the study. Polycythaemia was defined as Haemoglobin (Hb)>16.5 g/dL and Haematocrit (Hct)>48%. All data were collected in Microsoft Excel. Prephlebotomy haematologic values such as Hb and Hct were recorded for all patients. Status of Janus Kinase 2 (JAK2) mutation analysis was recorded from departmental archives when available. Categorical variables were expressed as counts and percentages; continuous variables were expressed as means, medians and ranges. The Pearson’s correlation coefficient was used to correlate pre- and post-phlebotomy Hb and Hct values. A paired t-test was used to determine whether the drop in Hb and Hct was statistically significant. A p-value <0.05 was considered statistically significant. Results: The study included 104 cases and showed male predominance with a male-to-female ratio of 51:1. The patients ranged in age from 23 to 73 years, with a mean age of 47 years. The average fall in Hb was 1.2 g/dL and the average fall in Hct was 3.6 percentage points after a single session of therapeutic phlebotomy (approximately 350 mL). The post-phlebotomy drop in Hb of ≥1 g/dL was observed in 81 (77.8%) patients, while 23 (22.1%) patients showed a drop < 1 g/dL. It was noted that 36 (34.6%) patients underwent multiple repeated sessions of therapeutic phlebotomy within eight weeks to bring Hb and Hct to the normal range. Conclusion: Therapeutic phlebotomy, involving removal of 300-400 mL of blood, can reduce Hb by about 1 g/dL and is recommended in polycythaemia to reduce the risk of arterial and venous thrombotic events. Polycythemia, irrespective of the cause, should be treated with aspirin in addition to therapeutic phlebotomy to maintain Hct below 45%.

Hollow fiber flow field-flow fractionation enables high-quality Extracellular Vesicle isolation from minimal plasma samples in polycythemia vera liquid biopsy.

Long-term efficacy and safety of ropeginterferon alfa-2b under its HIDAT regimen for the treatment of polycythemia vera.

Polycythemia vera (PV) is an insidious and progressive myeloproliferative neoplasm (MPN) characterized by an increase in red blood cell mass, which is almost always associated with a mutation in the Janus kinase 2 (JAK2) 2 gene. It can be complicated by pulmonary hypertension (PH). PH due to MPN is classified in WHO group 5: PH due to various chronic diseases with poorly characterized or understood mechanisms. Furthermore, the mechanisms of PH can hemodynamically differ between precapillary, postcapillary, and combined postcapillary and precapillary PH. We describe a case of combined pre- and post-postcapillary PH in a patient with newly diagnosed PV. Due to the diverse pathways of PH in PV, such as chro­nic thromboembolic PH, pulmonary arteriopathy, and left-sided heart dise­ase, the ideal therapeutic approach for patients with PH and PV has not been established. Case reports have demonstrated that JAK inhibition with ruxolitinib improved MPN-associated PH, leading to the initiation of this therapy in our patient.

In recent years, the expanding clinical use of Janus kinase inhibitors (JAKi) has driven notable progress in rheumatoid arthritis (RA) treatment, improving patient outcomes and spurring research to optimize their efficacy and safety. We performed a comprehensive bibliometric assessment on 1566 articles sourced from the Web of Science Core Collection. We conducted a systematic exploration of the development process and the core driving forces behind JAKi research for RA treatment using CiteSpace to reveal inherent patterns, track evolving trends, and pinpoint influential components in this research area. What is more, we used R 4.4.2 to conduct a time-trend analysis of the annual publications. Our findings revealed that the USA holds a preeminent position in JAKi research for RA treatment. Through an institutional co-occurrence analysis, we identified Pfizer Inc. as a central driving force, playing a pivotal role in advancing research and development in this area. In the author collaboration network, Takeuchi Tsutomu emerged as a vital scholarly contributor, as evidenced by his high publication centrality, indicating his significant influence on the research community. Journal co-occurrence analysis further highlighted ANN RHEUM DIS as a highly influential publication outlet for JAKi research related to RA. Keyword clustering revealed ten core themes: "activation," "inadequate response," "network meta-analysis," "jak inhibitors," "efficacy," "ankylosing spondylitis," "ulcerative colitis," "quality of life," "polycythemia vera," and "gout." In the keyword timeline viewer analysis, "inadequate response" and "ulcerative colitis" recently emerged as significant research topics within the JAKi-RA research landscape. Citation burst analysis indicates that "risk" and "management" in the clinical application of JAKi, as well as research related to "atopic dermatitis" and "tocilizumab," have emerged as prominent research frontiers, attracting increased attention from the research community and expanding the therapeutic applications of JAKi. Our research indicates that comorbid IMIDs associated with RA, along with the adverse reactions of JAKi during clinical application, will remain pressing challenges to be addressed in the future. As JAKi become more widely and deeply integrated into clinical management, their significant potential and value are increasingly evident, warranting further research.

Elevated serum erythropoietin level in JAK2+ polycythemia vera with small vessel Budd-Chiari syndrome.

In our study, we investigated the ototoxic interaction of Janus kinase (JAK) inhibition in combination with aminoglycosides. The therapeutic landscape of JAK inhibitors has undergone a significant transformation since 2018, characterized by a rapid increase in FDA approvals for this class of drugs. Initially approved for conditions like myelofibrosis and polycythemia vera, the indications have expanded to include several inflammatory conditions, such as psoriatic arthritis, ulcerative colitis, and rheumatoid arthritis, leading to a substantial increase in patients exposed to these therapies. The potential interactions of this drug class with ototoxins are unknown. C57Bl/6N mice corrected for Cadherin23 (Cdh23tm2.1/kjn) were treated with kanamycin (KM), (500mg/kg, subcutaneously, twice daily for 14d) either alone or with lipopolysaccharide (LPS) (1mg/kg, intraperitoneally, 3 times during the treatment) to mimic inflammation from gram-negative infections. A separate group also received momelotinib (MMB), a dual JAK1/JAK2 inhibitor, at 50mg/kg or 20mg/kg by oral gavage twice daily for 14 days alongside KM and LPS. Hearing function was assessed through auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE), while cochlear damage and hair cell loss were evaluated using whole mount staining for phalloidin and myosin 7a. Inhibition of JAK1 and JAK2 by MMB caused a substantial increase in the hearing loss and cochlear damage in animals exposed KM and LPS as measured by ABR, DPOAE, and outer hair cell (OHC) counts. JAK1 and JAK2 inhibition worsens cochlear damage in mice exposed to aminoglycosides.

Polycythemia vera (PV) and essential thrombocythemia (ET) are associated with a well-recognized increased risk of thrombotic events, bleeding, and all-cause mortality, but the frequency of these outcomes during treatment has rarely been assessed in large cohorts. In this nationwide, population-based study, we analyzed 2604 PV and 3141 ET patients using multiple Swedish health care registers, covering 43 612 patient-years. Rates of arterial and venous events, major bleeding, and all-cause mortality (ACM) were evaluated across therapies. Unexpectedly, 42.3% of low-risk PV patients and 29.7% of very low/low-risk ET patients received hydroxyurea (HU) during follow-up. High-risk PV patients treated with interferon (IFN) exhibited the lowest arterial event rate (2.21 per 100 patient-years). In high-risk ET, patients with IFN therapy experienced the lowest arterial and venous event rates (1.55 and 0.44 per 100 patient-years). Advanced age and leukocytosis at diagnosis independently predicted thrombosis, bleeding, and ACM in both PV and ET. Multivariable analysis showed that HU and IFN were associated with reduced ACM risk; HU also conferred protection against thromboembolism and major bleeding. This study highlights risk factors associated with complications during treatment in a real-world context and reinforces the role of HU and IFN as first-line therapies in PV and ET.

Polycythemia in felines is a rare and often underdiagnosed condition characterized by an increased mass of circulating erythrocytes and a persistently elevated hematocrit. Its absolute form can be primary, as in polycythemia vera, or secondary, associated with hypoxic stimuli or inappropriate erythropoietin secretion. This condition predisposes to hyperviscosity syndrome, with varied and sometimes severe clinical manifestations. The initial treatment of choice is phlebotomy, due to its effectiveness in immediately reducing hematocrit. This article reports the clinical case of a mixed-breed cat diagnosed with absolute polycythemia, submitted to therapeutic phlebotomy. The report emphasizes the hematological response obtained and discusses the need for continuous monitoring and complementary therapeutic approaches for the management of the disease.

Polycythemia vera (PV) is a myeloproliferative neoplasm. The presence of JAK2 mutations is a major diagnostic criterion for PV. PV is linked to chronic inflammation and an increased risk of thrombosis, and inflammation plays a significant part in the pathophysiology of PV. Testing for JAK2 mutations is expensive and is not available in all laboratories. Simple inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), are evaluated in this study as potential diagnostic markers for differentiating patients with PV from other patients with polycythemia. We conducted a retrospective study of the clinical and laboratory data from 281 patients with polycythemia (110 with PV and 181 with secondary polycythemia (SP)) who attended Ghaem Hospital. The diagnosis of PV was established based on the World Health Organization criteria. Individuals who did not meet the criteria were classified as having SP. The median NLR, PLR, and SII in the PV group were considerably elevated compared to the SP group (NLR: 5.00 vs. 1.86, PLR: 261.3 vs. 94.0, SII: 2432.9 vs. 368.8, p < 0.001 for all). The receiver operating characteristic analysis revealed that NLR, PLR, and SII were highly effective in differentiating PV patients from the SP group. Each of these tests showed sensitivities and specificities over 85% and an area under the curve of more than 0.9. SII, NLR, and PLR were all higher in PV than SP, suggesting that these biomarkers, particularly SII, might be helpful in the diagnosis of PV.

Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative neoplasms (MPNs), often associated with mutations in JAK2, CALR, and MPL. Differentiating PV from ET can be challenging in borderline cases, particularly when hemoglobin (Hb), hematocrit (Hct) and erythropoietin (EPO) values are inconclusive. Functional iron parameters and JAK2 variant allele frequency (VAF) may provide additional discriminatory value. To assess the diagnostic utility of transferrin saturation index (TSI), serum ferritin, EPO, and JAK2 VAF in distinguishing PV from ET, and to evaluate their association with mutational profiles. We conducted a retrospective, single-center study including 260 adult patients diagnosed with PV or ET between 2009 and 2024. Demographic, clinical, molecular, and laboratory parameters—including ferritin, TSI, EPO, Hb, Hct, and JAK2 VAF—were analyzed. Comparative and correlation analyses were performed using appropriate statistical tests. Compared to ET, patients with PV had significantly lower ferritin (median: 35.65 vs. 95.05 ng/mL), TSI (12.9% vs. 21.64%), and EPO (2.23 vs. 6.11 mIU/mL), but higher Hb (17.7 vs. 14.3 g/dL) and Hct (54.6% vs. 43.0%) (all p < 0.001). TSI discriminated PV from ET better than ferritin (p < 0.001 vs. p = 0.128). Among JAK2-mutated cases, VAF was higher in PV than ET (median: 48% vs. 21%, p = 0.003). VAF correlated inversely with ferritin, TSI, and EPO, and positively with Hct. TSI and JAK2 VAF outperform ferritin as diagnostic markers to differentiate PV from ET. Integrating functional iron parameters with molecular data improves diagnostic accuracy, particularly in clinically ambiguous cases, and supports their inclusion in MPN diagnostic algorithms.

Polycythemia vera (PV) and Essential thrombcythemia (ET) are myeloproliferative neoplasms (MPNs) that can progress to secondary myelofibrosis, a complication associated with increased mortality. Circulating CD34-positive cells at diagnosis can be used to distinguish primary myelofibrosis from other MPNs with a threshold of 10/µL. In this study, we evaluate the interest of serial CD34-positive cell quantifications during the follow-up of MPNs. We retrospectively include 180 patients with MPN (90 ET, 55 PV and 35 myelofibrosis) with at least two measurements of circulating CD34-positive cells. CD34-positive cell count showed an AUC of 0.901 for the diagnosis of post-ET/PV myelofibrosis, with a sensitivity of 54.8%, a specificity of 99.5%, a PPV of 89.5% and a NPV of 96.3% for the threshold of 15 cells/µL. The decreased sensibility could be explained by an impact of cytoreductive treatments. Then we focused on primary and secondary myelofibrosis (MF) and found that patients achieving partial or complete response (per IWG-MRT criteria) had lower CD34-positive cell levels. Finally, CD34-positive cell levels had a prognostic impact on overall survival in MF, a count ≥ 100/µL is predictive of a higher risk of death (HR = 2.9 [1.5–5.9]), independently of DIPSS classification. In conclusion, monitoring of circulating CD34-positive cells is valuable for evaluating both disease progression and prognosis in MPN patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00277-026-06755-1.

Recent advancements in aptamer-mediated theranostics in the management of hematological disorders.

Cytoreductive treatment differentially affects platelet size and cytoskeletal megakaryocyte organization during thrombopoiesis in myeloproliferative neoplasms.

Platelets display immunophenotypic alterations and dysregulated transcriptomic signature in Philadelphia-negative myeloproliferative neoplasms.

Integrated one-pot RPA-CRISPR/Cas13a platform enables ultrasensitive and field-deployable JAK2 V617F detection for myeloproliferative neoplasm diagnosis.

Introduction: Ropeginterferon alfa-2b is an emerging treatment for polycythemia vera, with growing interest in its application for essential thrombocythemia and early myelofibrosis due to its extended dosing intervals and favorable tolerability profile. However, real-world evidence regarding its dosing strategies and titration practices remains limited. Objective: This study examined seven younger patients, all under 60 years of age, who were treated with ropeginterferon alfa-2b. Materials and Methods: This study is a retrospective medical records review of consecutive patients from seven hospitals. Treatment was initiated at a dose of 250 micrograms, with a maintenance dose of 500 micrograms. Results: The regimen demonstrated good safety and tolerability in this real-world setting. Hematological responses were observed, along with a meaningful reduction in JAK2V617F variant allele frequency across the patient cohort. Conclusions: These findings show that the use of high-initial-dose accelerated titration (HIDAT) regimen of ropeginterferon alfa-2b is a safe and effective treatment option for younger patients with myeloproliferative neoplasms.

To verify the clinical benefit of ropeginterferon alfa-2b (ropegIFN) and evaluate its cost-effectiveness compared with hydroxycarbamide or ruxolitinib for patients with polycythemia vera (PV) under the National Health Insurance (NHI) system in Japan. The cost-effectiveness of ropegIFN compared with hydroxycarbamide or ruxolitinib was evaluated for patients with PV requiring cytoreductive therapy (without prior cytoreductive therapy) and resistant or intolerant to hydroxycarbamide. According to previous reports, patients with PV who achieve a molecular response with a JAK2V617F allele burden < 10% tend to maintain hematologic responses even after discontinuing interferon treatment. Therefore, in these analyses, patients who achieved a molecular response with JAK2V617F burden < 10% discontinued ropegIFN treatment. Compared with hydroxycarbamide, ropegIFN yielded an incremental effectiveness of 0.440 quality-adjusted life years (QALYs), indicating a higher QALY gain. The incremental costs were 128,001,730 yen, and the incremental cost-effectiveness ratio (ICER) was 291,092,030 yen/QALY. Compared with ruxolitinib, the incremental effectiveness of ropegIFN was 1.278 QALYs, while the total costs were reduced by 18,025,182 yen, which resulted in a dominant ICER. These results suggest that ropegIFN may be cost-effective compared with ruxolitinib in patients with PV who are resistant or intolerant to hydroxycarbamide under the NHI system in Japan.

Background: Ropeginterferon alfa-2b (Ropeg-IFNa) is increasingly used in myeloproliferative neoplasms (MPN), particularly polycythemia vera, but real-world data across subtypes are limited. We evaluated clinical and molecular responses to Ropeg-IFNa in routine practice. Methods: We retrospectively analyzed 20 JAK2V617F-positive MPN patients treated at a tertiary center. Baseline features, dosing, treatment line, hematologic responses, adverse events, and serial JAK2V617F variant allele frequency (VAF) were extracted from records. Results: Median age at initiation was 53 years; 55% were ELN high-risk. Ropeg-IFNa was started first-line or after peginterferon alfa-2a, hydroxyurea, or a tapered JAK2 inhibitor. Mean treatment duration was 14 ± 11 months at 195 ± 143 µg Q2W. Hematologic control increased from 45% at the start to 60% at the last follow-up. Among patients with serial molecular monitoring (n = 11), median JAK2V617F VAF declined from 21.2 to 12.7%. Ropeg-IFNa was generally well tolerated; adverse effects were mostly manageable, although 3/20 (15%) discontinued due to side effects, including mood disturbances, while others continued with supportive care and dose adjustments. Conclusions: In this single-center cohort, Ropeg-IFNa was tolerable and associated with improved hematologic control and modest VAF reductions, supporting its use in multi-subtype MPN cohorts. These findings underscore the value of longitudinal driver-mutation monitoring during therapy.