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Background: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by bone marrow fibrosis associated with substantial morbidity and mortality. The therapeutic landscape for MF has advanced with the development of Janus kinase inhibitors (JAKis) like ruxolitinib (RUX), fedratinib (FED), pacritinib (PAC), and momelotinib (MMB), aiming to alleviate symptoms and enhance patient comfort. Methods: A network meta-analysis was conducted to assess the efficacy and safety of eleven JAKi treatment regimens across nine randomized controlled trials (RCTs) with a total of 2340 participants. Outcomes were evaluated in terms of spleen volume reduction (SVR), total symptom score reduction (TSSR), hematological safety profiles, and overall survival (OS). Results: RUX and MMB were superior in achieving SVR and TSSR, with significant dose-response relationships observed. PAC and MMB were associated with a decreased risk of grade 3/4 anemia and thrombocytopenia compared to other JAKis. However, no substantial benefits in OS were observed with newer JAKis compared to RUX. The poorer OS outcomes with certain PAC dosages were likely influenced by baseline patient characteristics, particularly severe cytopenias. Conclusion: The introduction of JAKis significantly changed the treatment of MF. This meta-analysis reaffirms the core role of RUX and positions MMB as a potentially powerful alternative for treating symptoms and reducing spleen size. Meanwhile, MMB and PAC have a positive effect on anemia in MF while FED is more tolerable for patients with thrombocytopenia. However, it should be noted that these results are influenced by baseline patient characteristics, particularly cytopenias, which affects both management and overall survival. Therefore, there is an urgent need for personalized dosing strategies to optimize the balance between efficacy and safety, with careful consideration of patient-specific factors. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023424179.

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BACKGROUND: Primary myelofibrosis (PMF) is the most advanced subtype among the classic Philadelphia chromosomenegative myeloproliferative neoplasms (MPNs). A majority of patients carry one of three mutually-exclusive somatic driver mutations: JAK2 (60-65%), CALR (20-25%), or MPL (5%). Co-occurrence of these mutations is rarely reported. Here we report a case with a triple positive combination of JAK2, CALR and MPL driver mutations. CASE PRESENTATION: A 69-year-old male was admitted to hospital for acute exacerbation of chronic obstructive pulmonary disease (COPD) and was found to have splenomegaly and leukocytosis. Nextgeneration revealed JAK2, CALR, MPL mutations, and additional variants in SF3B1, SRSF2, and STAG2. The patient was diagnosed with PMF and treated with ruxolitinib and COPD therapy. Due to nausea, the ruxolitinib dose was reduced. After therapy, spleen volume decreased and hematologic responses were poor. Another genetic mutation of ASXL1 was later found. After adjusting the medication and adding antiemetics, the patient's condition improved. CONCLUSIONS: The rare coexistence of JAK2, CALR, and MPL mutations challenges the assumption of their mutual exclusivity. Further study of these mutations is essential for developing better treatment strategies.

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Identification of driver genes and pathological bone marrow diagnosis were considered essential for subclassification of MPN in the revised 4th edition of the WHO classification, and this remained nearly unchanged in the 5th edition. Pathological diagnosis of primary myelofibrosis/pre-fibrotic stage by biopsy is now feasible and is becoming standardized. Progressive myelofibrosis and blast transformation are the advanced forms of MPN, and various therapeutic interventions for these forms have been devised. Observation of activated megakaryocytes on evaluation of megakaryocyte morphology could predict the progression of myelofibrosis. This paper describes recent progress in pathological diagnosis of MPN and how it is performed in practice.

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Myelofibrosis should be diagnosed according to the WHO classification (2022, 5th Ed.) and International Consensus Conference 2022 criteria. Testing for driver mutations in the three genes JAK2, CALR, and MPL is recommended to ensure a definitive diagnosis. Ruxolitinib is the only JAK inhibitor currently approved in Japan, but momelotinib is under regulatory review. The MOMENTUM study showed similar spleen volume reduction at 24 weeks and MFSAF-TSS reduction as the COMFORT study of ruxolitinib. Momelotinib acts on ACVR1 and, therefore, improves anemia through suppression of hepcidin. Anemia and/or transfusion dependency are known to be associated with overall survival duration. Consequently, supportive care measures such as ESA and danazol in lieu of transfusion should be considered in addition to JAK inhibitor selection. Mean survival after discontinuation of JAK inhibitors is 11 to 14 months. Pacritinib (not approved in Japan) is suitable for MF patients with thrombocytopenia. JAK inhibitor selection and supportive care by ESA or danazol in lieu of transfusion should be considered. Many classes of drugs other than JAK inhibitors for myelofibrosis are under investigation.

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We report the case of a 54-year-old healthy Han Chinese male presenting with fever, pallor, erythematous subcutaneous nodules on the limbs, and significant anemia as indicated by routine blood tests, with no response to antimicrobial therapy. Initial skin biopsy was inconclusive. The erythematous subcutaneous nodules on the limbs rapidly progressed to widespread subcutaneous nodules across the body, with worsening anemia. Bone marrow biopsy revealed multifocal fibroblastic proliferation with focal fibrosis, classified as MF-2, and positive for the JAK2V617F mutation alongside SRSF2 positivity. Whole-body PET-CT scans did not reveal any lymph nodes or suspect lesions with high SUV uptake. A subsequent skin biopsy identified the condition as nodular panniculitis (NP), leading to a final diagnosis of primary myelofibrosis(PMF)with NP. The patient initially received treatment with oral ruxolitinib and prednisone acetate, resulting in normalization of body temperature, resolution of erythematous nodules, and normalization of blood parameters.

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PURPOSE OF REVIEW: Allogeneic hematopoietic cell transplantation is the only potentially curative treatment for myelofibrosis. This review discusses issues not well-covered by existing guidelines: timing of transplant, pre-transplant spleen management and alternative donors; providing our approach to these situations. RECENT FINDINGS: Research continues to allow better identification, by better risk stratification and advances in understanding likelihood of durable JAKi response, which patients are likely to derive benefit from upfront transplant versus those for whom delayed transplant may be more appropriate. Several options of JAKi therapy provide a non-surgical option for pre-HCT splenomegaly management, allowing some patients to avoid risks associated with splenectomy. Recent years have also seen a sharp spike in haploidentical donor transplants, along with narrowing of the gap in outcomes between donor types. Continuous enrollment in prospective studies or well-designed registries is required to generate the high-quality data needed to develop better decision tools for these scenarios.

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BACKGROUND: It has been described in mice models that myeloproliferative neoplasm (MPN) with JAK2-V617F mutation has an increased expression of programmed death-ligand 1 (PD-L1) in megakaryocytes leading to cancer immune evasion by inhibiting the T-lymphocytes. AIMS: To quantify and compare the PD-L1 expression on bone marrow (BM) of patients with MPN JAK2 positive, negative, and normal controls. METHODS: We collected BM of patients with MPN JAK2 positive, negative and normal controls from 1990 to 2019. We also created a scoring system to quantify PD-L1 expression in megakaryocytes. RESULTS: We obtained 14 BM with JAK2 positive PMF, 5 JAK2 negative PMF, and 10 patients with normal BM biopsies. PD-L1 expression was higher in the JAK2 positive group compared with the control group with a score of 212.6 versus 121.1 (t-value 2.05, p-value 0.025). In addition, the score was higher in the PMF group regardless of JAK2 mutational status when compared with the control group with score of 205.9 versus 121.1 (t-value 2.12, p-value 0.021). There was no difference in the PD-L1 score between the JAK2 negative versus the control group 187.2 versus 121.1 (t-value 1.02, p-value 0.162). CONCLUSION: These findings suggest that PMF patients with a JAK2 mutation have a higher PD-L1 expression in megakaryocytes compared with the control group. We postulate that the combination of checkpoint and JAK2 inhibitors may be an active treatment option in JAK2 mutated PMF given the higher PD-L1 expression.

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Autoimmune myelofibrosis (AIMF) is a distinct, underrecognized, and rare cause of bone marrow fibrosis. It carries a favorable outcome and responds well to immunosuppression. Systemic lupus erythematosus is the most common association with AIMF, but there are other cases of associated autoimmune disorders defined in the literature. A 44-year-old female presented to hospital with a 1-month history of fatigue, malaise, and jaundice. She was found to be pancytopenic with elevated liver enzymes. Tests for Janus kinase 2, myeloproliferative leukemia, and calreticulin mutations were negative. Extensive investigations for hemolytic anemia including direct antiglobulin test, flow cytometry for paroxysmal nocturnal hemoglobinuria, testing for hereditary hemoglobinopathies, and hereditary red cell membrane disorders were non-contributory. Antinuclear antibody was positive at > 1,280, immunoglobulin G was 17.04 g/L, and anti-smooth muscle antibody (ASMA) was positive at 1:40. Characteristic features of AIMF on bone marrow biopsy led to the diagnosis of AIMF. The patient was started on prednisone 1 mg/kg with prolonged taper. Fibroscan and liver biopsy were consistent with cirrhosis and workups for other causes of liver dysfunction were unremarkable. She met criteria for diagnosis of autoimmune hepatitis (AIH). The pancytopenia and liver enzymes improved with prednisone. After 1 year of clinical stability, the patient had relapse of disease with pancytopenia, elevated liver enzymes, and similar fibrosis on repeat bone marrow biopsy. Prednisone was reinitiated at 1 mg/kg, and she was started on mycophenolate mofetil (MMF). Prednisone was tapered, and she continues to have an excellent response on MMF alone. We report a case of AIMF associated with AIH, complicated by non-immune hemolysis. AIMF is rare, and its association with AIH is described in only four other cases in the English-language literature. Overlapping biochemical features of AIH and non-immune hemolysis, which has not been well described in AIMF, lead to significant diagnostic complexity and delay. Despite this, a rapid response to corticosteroids was observed including reversal of profound transfusion dependence, normalization of hemoglobin, and reversal of biochemical evidence of hepatic inflammation. A shared pathogenesis of autoimmune fibrosis in both the bone marrow and liver is speculative but suggested by the temporal association in this case.

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Ruxolitinib (RUX), a Janus kinase 2 (JAK2) inhibitor, and lenalidomide (LEN), an immunomodulatory agent, have recently been proposed as a combined treatment for myelofibrosis (MF). This combination has demonstrated improved efficacy, safety, and tolerability compared to monotherapy. To further refine these findings, an efficient analytical tool is needed to simultaneously determine RUX and LEN concentrations in blood plasma. This tool would enable the study of their pharmacokinetics, drug-drug interactions, and therapeutic monitoring during MF therapy. Unfortunately, such a method has not been existed in the literature. This study presents the first HPLC method with UV detection for the simultaneous quantitation of RUX and LEN in plasma. The method was validated according to the ICH guidelines for bioanalytical method validation. It exhibited linearity in the concentration ranges of 10 to 3150 ng mL- 1 for RUX and 80 to 5200 ng mL- 1 for LEN. The limits of quantitation were determined to be 25 and 90 ng mL- 1 for RUX and LEN, respectively. All other validation parameters were satisfactory. The HPLC-UV method was successfully employed to study the pharmacokinetics and drug-drug interactions of RUX and LEN in rats following oral administration of single doses. The results demonstrated that the pharmacokinetics of both drugs were changed substantially by their coadministration. LEN exhibited synergistic effects on the maximum plasma concentration (Cmax) and total bioavailability of RUX, meanwhile it exhibited diminishing effect on the values of volume of distribution (Vd) and clearance (CL). Additionally, RUX decreased the Cmax and total bioavailability of LEN, meanwhile it increased its Vd and CL. These data suggest that the use of RUX, as a combination with LEN, is a better therapeutic approach for MF, compared with RUX as a monotherapy. The effects of LEN on the pharmacokinetics of RUX should be considered and can be useful in determining the appropriate RUX dosage and dosing regimen to achieve the desired therapeutic effect when used as a combination therapy with LEN. The method's environmental friendliness was confirmed through three comprehensive tools. This method represents a valuable tool for determining the appropriate dosage and dosing regimen of RUX in combination therapy with LEN to achieve the desired therapeutic effect. Furthermore, it can aid in predicting drug distribution in different patients and assessing the drug accumulation or insufficient drug levels in specific body compartments.

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The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted the diagnosis and management of tuberculosis (TB), a major public health issue. This case report discusses a 70-year-old female with post-polycythemia vera myelofibrosis (post-PV MF) treated with ruxolitinib who developed miliary TB amidst a COVID-19 infection. The patient presented with a flu-like syndrome over the past week with fatigue and weight loss the last month. When she was admitted to the hospital, the real-time polymerase chain reaction (RT-PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was positive. Despite the typical COVID-19 presentation, her clinical and radiographic features raised suspicion for disseminated TB. Diagnostic tests, including bronchoscopy and PCR for Mycobacterium tuberculosis, confirmed miliary TB. She was treated with a standard antitubercular regimen, leading to symptomatic improvement. The interplay between COVID-19 and TB is complex, with COVID-19-induced immunosuppression, particularly lymphocytopenia, facilitating TB reactivation. Additionally, ruxolitinib, a Janus kinase (JAK) inhibitor used for myelofibrosis, impairs immune defense mechanisms, increasing infection risk, including TB. Prompt and accurate diagnosis of TB in the context of COVID-19 is crucial for effective management and improved patient outcomes. Clinicians should remain vigilant for TB reactivation in patients undergoing treatments such as ruxolitinib and consider alternative diagnoses despite positive SARS-CoV-2 tests. This report highlights the necessity for a comprehensive evaluation and timely intervention to mitigate the compounded risks of COVID-19 and TB.

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Myelofibrosis (MF) is a clonal disorder of hematopoietic stem cells characterized by altered bone marrow function and fibrosis. The aim of this narrative review is to report on the most recent epidemiologic data and to discuss features of MF and current strategies for the management of this condition in clinical practice. MF features covered by our review will include: characteristics of patients with MF; myeloproliferative and myelodepletive phenotypes; MF-associated thrombosis and bleeding; risk of infections; prefibrotic and overt PMF; secondary MF. Finally, we will discuss a few aspects of MF management in clinical practice and suggest strategies for its optimization and standardization. The focus of our paper is on Italy, but relevant data from other countries will also be reviewed.

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OBJECTIVES: There is limited data on the incidence, prevalence, and treatments for myelofibrosis (MF) in Germany. This retrospective study examined claims data from 3.3 million insured individuals, spanning from 2010 to 2021. METHODS: Four sensitivity scenarios were explored to identify cases of MF. Point prevalence and cumulative incidence of MF were determined as of December 31, 2021, and within 2021, respectively. A cross-sectional analysis used the main scenario definition of MF to identify cases and evaluate the period prevalence of patients receiving treatment for symptoms and/or splenomegaly, including first-line (1L) Janus kinase inhibitor (JAKi), second-line, or further (2L+) MF-related treatment therapies during 2021. The prevalence of anemia treatment was also reported. RESULTS: The estimated standardized point prevalence of MF on December 31, 2021, was 9.9-12.4 cases per 100 000 persons, and cumulative incidence in 2021 was 1.2-1.8 cases per 100 000 persons. Standardized period prevalence in 2021 for MF patients receiving 1L JAKi and/or 2L+ MF-related treatment was 4.0 cases per 100 000. Among these patients, 47.1%-53.7% required treatment for anemia, resulting in a period prevalence of 1.9-2.2 cases per 100 000 individuals. CONCLUSION: The data reveal gaps in MF treatments and the need to improve patient quality of life.

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Absence status epilepticus (ASE) is a rare but treatable condition, and when present in older adults, it can be misinterpreted as encephalopathy or behavioral changes. Our case discusses a 63-year-old patient with myelofibrosis and allogeneic stem cell transplant with late-onset de novo status epilepticus. This case report adds to the rare body of literature discussing de novo ASE whose clinical presentation can be indistinguishable from other encephalopathic or behavioral conditions. Moreover, its occurrence during oncologic treatment warrants clinicians to be on the lookout for similar presentations and encourages future reports of this condition in association with similar therapies. This case report provides value to providers treating patients with similar oncologic therapies and highlights the need for ASE to be further studied as it is a possible rare complication of allogeneic transplantation of stem cells.

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Introduction: IDH2 mutation is an unfavorable prognostic factor in patients with primary myelofibrosis (PMF) but its effect on myelofibrosis (MF) remains largely unclear. Methods: In this study, we aimed to elucidate the roles of IDH2 mutation in the development and progression of MF by transcriptomic and molecular techniques using the Idh2 R172K transgenic mice. Results: We found that thrombopoietin (TPO)-overexpressed Idh2 R172K (Idh2 R172K + TPO) mice had accelerated progression to MF, compared with TPO-overexpressed Idh2-wild (WT + TPO) mice, showing activation of multiple inflammatory pathways, among which nuclear factor κB (NFκB) was the most significantly enhanced. Single-cell transcriptomes of the marrow cells in early MF showed that S100a8/a9 expression was mainly confined to neutrophil progenitors in the WT + TPO mice, but highly expressed in several types of myeloid precursor cells, including the megakaryocyte progenitors in the Idh2 R172K + TPO group. Furthermore, Idh2 R172K mice at age of 18 months had larger spleens, increased S100a8/a9-Tlr4 expression, and elevated serum S100a8/a9 levels compared with WT mice. PMF patients with IDH2 mutations had higher bone marrow plasma S100A8/A9 levels than those without IDH2 mutations. Conclusion: Overall, our findings showed that IDH2 mutation induced proinflammatory effects, which further exacerbated MF, as evidenced by the increase in S100a8/a9 levels and NFκB hyperactivation in Idh2 R172K + TPO mice.

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Current consensus recommends hematopoietic cell transplantation (HCT) for patients with myelofibrosis with intermediate or high-risk disease and age of less than 70 years. However, a higher chronological age should not be prohibitive for the eligibility decision in general, acknowledging that current life expectancy for the general population aged 70 years is ∼15 years, and current numbers of patients transplanted at 70 years or older is steadily increasing. The following study aimed to evaluate characteristics and outcomes of HCT in 115 myelofibrosis patients aged 70 years or older. This is a retrospective multicenter study, using the German Registry for Stem Cell Transplantation and Cellular Therapy (DRST). Adult myelofibrosis patients were included who received HCT up until 2021. Patients with secondary leukemia were excluded. Main endpoints were HCT demographics over time and outcomes after HCT (including overall survival, relapse incidence, non-relapse mortality, and graft-versus-host disease/relapse-free survival). Numbers of HCT increased over the past decade, with a significant spike since 2019. Comorbidity status of transplanted patients improved over time, while reduced-intensity conditioning was the preferred HCT platform, especially in most recent years. The 3-year overall survival was 55% (95% confidence interval [CI], 44%-65%). The 1-year cumulative incidence of relapse was 7% (95% CI, 3%-13%) and the 1-year cumulative incidence of non-relapse mortality was 22% (95% CI, 14%-31%). The 3-year graft-versus-host disease and relapse-free survival was 37% (95% CI, 27%-47%). Driver mutation genotype (in particular, non-CALR/MPL genotype) appeared to be the only variable that was significantly and independently associated with better survival in multivariable analysis, whereas neither comorbidity index nor dose intensity of pre-transplant conditioning appeared to influence outcome. This study demonstrated feasibility of curative treatment with HCT for myelofibrosis aged 70 or older, with significant increases in HCT numbers and improved fitness of older adults over recent years.

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Myeloproliferative neoplasms (MPNs) are a group of rare chronic progressive blood cancers that vary widely in clinical presentation, yet all patients have a risk of disease progression and thrombotic complications. Diseases include primary myelofibrosis, polycythemia vera, and essential thrombocythemia. With current treatment approaches, most patients live a prolonged life, but many experience a complex of symptoms that negatively influence their functional status and quality of life. Although significant advances have been made in preventing arterial and venous complications while mitigating inflammatory processes, comprehensive palliative care can help address unmet complex physical and psychosocial needs on a long-term basis. This article, created by a multidisciplinary group of providers, offers an overview of MPNs so palliative care clinicians can better support patients with these hematologic cancers.

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Myelofibrosis (MF), a complex hematological malignancy, presents a diverse array of symptoms, including anemia, constitutional symptoms, bone marrow insufficiency, and splenomegaly. The latter, often necessitating blood transfusions, poses an essential obstacle to MF management. While conventional approaches predominantly involve the use of JAK inhibitors, the potential for exacerbating anemia introduces complexity to the treatment. Nonetheless, Momelotinib stands out as a promising pharmaceutical compound with the potential to revolutionize the field. Momelotinib is an ACVR1 antagonist and a dual inhibitor of the JAK1 and JAK2 enzymes. By targeting MF's hematological and fibrotic aspects, Momelotinib influences iron metabolism by regulating hepcidin. This results in reduced hepcidin expression and increased iron availability, ultimately leading to improved anemia and reduced dependency on blood transfusion. This study aims to provide a concise overview of the pathogenesis of MF and elucidate the mechanism of action of Momelotinib. Subsequently, our review offers a practical summary encompassing the effects of Momelotinib in monotherapy, combined comparative drug therapy, and its associated side effects. Additionally, we explore the application of Momelotinib in other cancer types and investigate predictors for treatment success. Furthermore, we examine the utilization of Momelotinib in patients with liver and kidney failure.

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Momelotinib, an oral Janus kinase (JAK) 1/2 and activin A receptor type 1 inhibitor, improved symptoms, splenomegaly, and anemia in patients with myelofibrosis (MF). This sub-analysis of SIMPLIFY-1 evaluated the efficacy and safety of momelotinib versus ruxolitinib in Japanese patients with JAK inhibitor (JAKi)-naïve MF. Patients were randomized 1:1 to receive momelotinib 200 mg once daily or ruxolitinib 20 mg twice daily (or modified based on label) for 24 weeks, after which patients could receive open-label momelotinib. The primary endpoint was splenic response rate (SRR; ≥ 35% reduction in spleen volume) at 24 weeks; main secondary endpoints were total symptom score (TSS) response (≥ 50% reduction) and transfusion independence (TI) rates. Fifteen Japanese patients (momelotinib, n = 6; ruxolitinib, n = 9) were enrolled; all completed treatment. At Week 24, SRR was 50.0% with momelotinib and 44.4% with ruxolitinib. TSS response rates were 33.3% and 0%, and TI rates were 83.3% and 44.4%. Any-grade treatment-related adverse event (TRAE) rates were 83.3% with momelotinib and 88.9% with ruxolitinib. Grade 3/4 TRAE rates were 0% and 55.6%, with specific events being anemia (55.6%) and vertigo (11.1%) with ruxolitinib. Momelotinib was well tolerated, improved spleen and symptom responses, and reduced transfusion requirements in Japanese patients with JAKi-naïve MF.

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Primary myelofibrosis (PMF) is the most aggressive of the myeloproliferative neoplasms and patients require greater attention and likely require earlier therapeutic intervention. Currently approved treatment options are limited in their selective suppression of clonal proliferation resulting from driver- and coexisting gene mutations. Janus kinase inhibitors are approved for symptomatic patients with higher-risk PMF. Additionally, most ongoing clinical studies focus on patients with higher-risk disease and/or high rates of transfusion dependency. Optimal treatment of early/lower-risk PMF remains to be identified and needs randomized clinical trial evaluations. Pegylated interferon alfa is recommended for symptomatic lower-risk PMF patients based on phase 2 non-randomized studies and expert opinion. Ropeginterferon alfa-2b (ropeg) is a new-generation pegylated interferon-based therapy with favorable pharmacokinetics and safety profiles, requiring less frequent injections than prior formulations. This randomized, double-blind, placebo-controlled phase 3 trial will assess its efficacy and safety in patients with "early/lower-risk PMF", defined as pre-fibrotic PMF or PMF at low or intermediate-1 risk according to Dynamic International Prognostic Scoring System-plus. Co-primary endpoints include clinically relevant complete hematologic response and symptom endpoint. Secondary endpoints include progression- or event-free survival, molecular response in driver or relevant coexisting gene mutations, bone marrow response, and safety. Disease progression and events are defined based on the International Working Group criteria and well-published reports. 150 eligible patients will be randomized in a 2:1 ratio to receive either ropeg or placebo. Blinded sample size re-estimation is designed. Ropeg will be administered subcutaneously with a tolerable, higher starting-dose regimen. The study will provide important data for the treatment of early/lower-risk PMF for which an anti-clonal, disease-modifying agent is highly needed.

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Primary myelofibrosis shows widespread fibrosis in the bone marrow and is part of myeloproliferative neoplasms in which gene mutations in hematopoietic stem cells lead to abnormal clonal expansion of one or more lineage of myeloid and erythroid cells and megakaryocytes. Janus kinase (JAK) inhibitors are the main therapeutic regimen for primary myelofibrosis which harbors gene mutations, resulting in continuous activation of JAK-STAT signaling pathway. Since JAK inhibitors modulate immunological state, the administration would have a potential for uveitis. A 67-year-old patient presented with weight loss of 10 kg in the past 2 years after his retirement. He showed normocytic anemia with anisocytosis and abnormal shape, as well as hepatosplenomegaly. Suspected of hematological malignancy, bone marrow biopsy led to the diagnosis of primary myelofibrosis (grade 2) with bizarre megakaryocytes and relative maintenance of myeloid and erythroid lineage. He started to have blood transfusion. Genomic DNA analysis of the peripheral blood showed a pathogenic variant in the exon 9 of calreticulin (CALR) gene while pathogenic variants in Janus kinase-2 (JAK2), and myeloproliferative leukemia virus oncogene (MPL) were absent. He began to have oral ruxolitinib 10 mg daily at the timepoint of 5 months after the initial visit and the dose was increased to 20 mg daily 8 months later but was discontinued further 4 months later because he showed the limited effect of ruxolitinib. He had blood transfusion every week or every 2 weeks in the following 2 months until he noticed blurred vision in the right eye. The right eye showed thick fibrin membrane formation in the anterior chamber in front of the pupil which prevented the fundus from visualization. The left eye showed no inflammation and optic nerve atrophy, sequel to tuberculous meningitis in childhood. The patient started to use 0.1% betamethasone six times daily and 1% atropine once daily as eye drops. A week later, fibrin membrane disappeared and the pupillary area with total iris posterior synechia was visible in the right eye. He regained the vision in the right eye and did not show relapse of uveitis only with topical 0.1% betamethasone. Uveitis might be related with the administration and discontinuation of ruxolitinib.