7,263 results match your criteria Agnogenic Myeloid Metaplasia With Myelofibrosis


Safety and efficacy of the combination of sonidegib and ruxolitinib in myelofibrosis: a phase 1b/2 dose-finding study.

Blood Adv 2020 Jul;4(13):3063-3071

Guy's and St Thomas' National Health Service Foundation Trust, Guy's Hospital, London, United Kingdom.

The sonidegib and ruxolitinib combination was assessed in an open-label study in JAK inhibitor-naive patients with myelofibrosis (MF). The primary objective of phase 1b was to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) and phase 2 was to assess spleen volume reduction at weeks 24 and 48. Fifty patients were enrolled. Read More

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http://dx.doi.org/10.1182/bloodadvances.2019001212DOI Listing

An overview of three myeloproliferative neoplasms.

Nursing 2020 Jun 27. Epub 2020 Jun 27.

Jill Brennan-Cook is an assistant clinical professor of nursing at Duke University School of Nursing in Durham, N.C.

A group of rare hematologic cancers, myeloproliferative neoplasms (MPNs) evolve when bone marrow dysfunction causes overproduction of one or more blood cell types. This article explores the diagnosis, treatment, and nursing care of patients diagnosed with one of three classic MPNs: essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Read More

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http://dx.doi.org/10.1097/01.NURSE.0000684184.44195.27DOI Listing

E-Cadherin Expression in Blastic Plasmacytoid Dendritic Cell Neoplasms: An Unrecognized Finding and Potential Diagnostic Pitfall.

Int J Surg Pathol 2020 Jul 1:1066896920938130. Epub 2020 Jul 1.

Department of Histopathology, The Christie NHS Foundation Trust, Manchester, UK.

E-cadherin is expressed in hematopoietic erythroid precursors, but to our knowledge, its expression in blastic plasmacytoid dendritic cell neoplasm (BPDCN) has not been described. We report a case of BPDCN showing strong expression of E-cadherin, arising in a patient with history of primary myelofibrosis. Four more cases of BPDCN tested all showed strong expression of E-cadherin. Read More

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http://dx.doi.org/10.1177/1066896920938130DOI Listing

Management of challenging myelofibrosis after JAK inhibitor failure and/or progression.

Blood Rev 2020 May 30:100716. Epub 2020 May 30.

UT Health San Antonio MD Anderson Cancer Center, University of Texas Health Science Center San Antonio, San Antonio, TX 78249, USA. Electronic address:

The myeloproliferative neoplasms (MPNs) encompass a heterogenous set of diseases that have variable survival, but in the setting of treatment refractory and progressive disease, prognosis has been characteristically poor. JAK inhibition with ruxolitinib or fedratinib therapy has become the first line treatment for symptomatic or intermediate to high risk myelofibrosis. However, after three years of ruxolitinib therapy, approximately half of all patients with myelofibrosis will likely have stopped treatment. Read More

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http://dx.doi.org/10.1016/j.blre.2020.100716DOI Listing

Favorable COVID-19 course despite significant comorbidities in a ruxolitinib-treated patient with primary myelofibrosis.

Eur J Haematol 2020 Jun 27. Epub 2020 Jun 27.

Department of Pneumology and Intensive Care Medicine, Faculty of Medicine, RWTH Aachen University, Aachen, Germany.

COVID-19 carries a high risk of severe disease course, particularly in patients with comorbidities. Therapy of severe COVID-19 infection has relied on supportive intensive care measures. More specific approaches including drugs that limit the detrimental "cytokine storm", such as Janus-activated kinase (JAK) inhibitors, are being discussed. Read More

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http://dx.doi.org/10.1111/ejh.13480DOI Listing

JAK2, CALR, and MPL Mutations in Egyptian Patients With Classic Philadelphia-negative Myeloproliferative Neoplasms.

Clin Lymphoma Myeloma Leuk 2020 May 16. Epub 2020 May 16.

Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; Clinical Pathology Department, Oncology Center Mansoura University (OCMU), Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Background: Genetic mutations have been proven to be one of the major criteria in the diagnosis and distinction of different myeloproliferative neoplasm (MPN) subtypes. Therefore, the aim of this study was to determine the molecular profile of Egyptian patients with MPN subtypes and correlate with clinicopathological status.

Methods: A series of 200 patients with MPNs (92 polycythemia vera, 68 essential thrombocythemia, and 40 primary myelofibrosis) were included in this study. Read More

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http://dx.doi.org/10.1016/j.clml.2020.05.011DOI Listing

Real-world non-interventional long-term post-authorisation safety study of ruxolitinib in myelofibrosis.

Br J Haematol 2020 Jun 24. Epub 2020 Jun 24.

Department of Hematology and Blood Coagulation, Medical University of Vienna, Vienna, Austria.

Primary objective of this non-interventional, post-authorisation safety study was to provide real-world safety data [incidence of adverse drug reactions (ADRs)/serious adverse events (SAEs)] on adult patients with myelofibrosis exposed/or not exposed to ruxolitinib. Key secondary objectives included the incidence/outcome of events of special interest (bleeding events, serious/opportunistic infections, second primary malignancies, and deaths). Overall, 462 patients were included [prevalent users = 260, new users = 32, non-exposed = 170 (inclusive of ruxolitinib-switch, n = 57)]. Read More

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http://dx.doi.org/10.1111/bjh.16729DOI Listing

Genomic heterogeneity in myeloproliferative neoplasms and applications to clinical practice.

Blood Rev 2020 May 19:100708. Epub 2020 May 19.

Wellcome Sanger Institute, Hinxton, Cambridgeshire, UK; Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK; Haematopathology and Oncology Diagnostics Service/ Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Hills Rd, Cambridge CB2 0QQ, UK. Electronic address:

The myeloproliferative neoplasms (MPN) polycythaemia vera, essential thrombocythaemia and primary myelofibrosis are chronic myeloid disorders associated most often with mutations in JAK2, MPL and CALR, and in some patients with additional acquired genomic lesions. Whilst the molecular mechanisms downstream of these mutations are now clearer, it is apparent that clinical phenotype in MPN is a product of complex interactions, acting between individual mutations, between disease subclones, and between the tumour and background host factors. In this review we first discuss MPN phenotypic driver mutations and the factors that interact with them to influence phenotype. Read More

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http://dx.doi.org/10.1016/j.blre.2020.100708DOI Listing

Myeloproliferative neoplasms treated with hydroxyurea, pegylated interferon alpha-2A or ruxolitinib: clinicohematologic responses, quality-of-life changes and safety in the real-world setting.

Hematology 2020 Dec;25(1):247-257

Department of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.

Real-world data of responses, quality-of-life (QOL) changes and adverse events in patients with myeloproliferative neoplasms (MPN) on conventional therapy (hydroxyurea ± anagrelide), pegylated interferon alpha-2A (PEG-IFNα-2A) or ruxolitinib are limited. We prospectively studied MPN patients receiving conventional therapy, PEG-IFNα-2A or ruxolitinib. Next-generation sequencing of 69 myeloid-related genes was performed. Read More

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http://dx.doi.org/10.1080/16078454.2020.1780755DOI Listing
December 2020

Risk of infections in patients with myeloproliferative neoplasms-a population-based cohort study of 8363 patients.

Leukemia 2020 Jun 16. Epub 2020 Jun 16.

Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.

Infections are a common complication in patients with many hematologic malignancies, however, whether patients with myeloproliferative neoplasms (MPN) also are at an increased risk of infections is largely unknown. To assess the risk of serious infections, we performed a large population-based matched cohort study in Sweden including 8 363 MPN patients and 32,405 controls using high-quality registers between the years 1992-2013 with follow-up until 2015. The hazard ratio (HR) of any infection was 2. Read More

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http://dx.doi.org/10.1038/s41375-020-0909-7DOI Listing

Sex determines the presentation and outcomes in MPN and is related to sex-specific differences in the mutational burden.

Blood Adv 2020 Jun;4(12):2567-2576

Division of Adult Hematology, Department of Medicine.

The factors underlying the variable presentation and clinical course of myeloproliferative neoplasms (MPNs) remain unclear. The aim of this study was to evaluate the independent effect of sex on MPN presentation and outcomes. A total of 815 patients with essential thrombocytosis, polycythemia vera, or primary myelofibrosis were evaluated between 2005 and 2019, and the association of sex with presenting phenotype, JAK2 V617F burden, progression, and survival was examined. Read More

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http://dx.doi.org/10.1182/bloodadvances.2019001407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322953PMC

A Rare Case of Essential Thrombocythemia with Coexisting and Driver Mutations.

J Korean Med Sci 2020 Jun 15;35(23):e168. Epub 2020 Jun 15.

Division of Hematology & Oncology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea.

Philadelphia-negative (Ph-) classical myeloproliferative neoplasms (MPNs) include polycythemia vera, essential thrombocythemia (ET), and primary myelofibrosis. Somatic driver mutations in the , , and genes serve as major diagnostic criteria of the Ph- MPNs and these mutations occur in a mutually exclusive manner. In this report, we describe the first case of ET harboring double mutations in V617F and . Read More

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http://dx.doi.org/10.3346/jkms.2020.35.e168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295601PMC

Assessment of effects of repeated oral doses of fedratinib on inhibition of cytochrome P450 activities in patients with solid tumors using a cocktail approach.

Cancer Chemother Pharmacol 2020 Jul 14;86(1):87-95. Epub 2020 Jun 14.

Bristol Myers Squibb, Summit, NJ, USA.

Purpose: Fedratinib, an oral selective kinase inhibitor with activity against both wild type and mutationally activated Janus kinase 2, has been approved for the treatment of adult patients with intermediate-2 or high-risk myelofibrosis by the US Food and Drug Administration. In vitro studies indicated that fedratinib was an inhibitor of several cytochrome P450 (CYP) enzymes. The primary objective of this study was to evaluate the effects of repeated doses of fedratinib on the activity of CYP2D6, CYP2C19, and CYP3A4 in patients with solid tumors using a CYP probe cocktail. Read More

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http://dx.doi.org/10.1007/s00280-020-04102-3DOI Listing

Reduced CXCR4-expression on CD34-positive blood cells predicts outcomes of persons with primary myelofibrosis.

Leukemia 2020 Jun 14. Epub 2020 Jun 14.

Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S. Matteo Foundation, Pavia, Italy.

The expression of the CXCR4 chemokine receptor on CD34-positive blood cells is reduced in persons with primary myelofibrosis (PMF). We analyzed the relevance of cytofluorimetric assessment of the percentage of CD34-positive blood cells that had a positive CXCR4 surface expression (CD34/CXCR4-se) in a large cohort of subjects with myeloproliferative neoplasms. Mean CD34/CXCR4-se was lower in subjects with PMF compared with those with essential thrombocythemia (ET) or polycythemia vera (PV). Read More

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http://dx.doi.org/10.1038/s41375-020-0926-6DOI Listing

Genomic characterization and prognostication applied to a Brazilian cohort of patients with myelofibrosis.

Int J Hematol 2020 Jun 13. Epub 2020 Jun 13.

Escola de Saude e Medicina da Universidade Catolica de Brasilia, Brasilia, Brazil.

Genomic characterization of patients with myeloproliferative neoplasms (MPN) may lead to better diagnostic classification, prognostic assessment, and treatment decisions. These goals are particularly important in myelofibrosis (MF). We performed target Next Generation Sequencing for a panel of 255 genes and Chromosome Microarray Analysis (CMA) in 27 patients with MF. Read More

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http://dx.doi.org/10.1007/s12185-020-02906-wDOI Listing

Epidemiology of the classical myeloproliferative neoplasms: The four corners of an expansive and complex map.

Blood Rev 2020 May 22:100706. Epub 2020 May 22.

Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, USA; Cancer Outcomes, Public Policy, and Effectiveness Research (COPPER) Center, Yale University, New Haven, USA. Electronic address:

The classical myeloproliferative neoplasms (MPNs), specifically chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), represent clonal myeloid disorders whose pathogenesis is driven by well-defined molecular abnormalities. In this comprehensive review, we summarize the epidemiological literature and present our own analysis of the most recent the Surveillance, Epidemiology, and End Results (SEER) program data through 2016. Older age and male gender are known risk factors for MPNs, but the potential etiological role of other variables is less established. Read More

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http://dx.doi.org/10.1016/j.blre.2020.100706DOI Listing

Enhanced engraftment of human myelofibrosis stem and progenitor cells in MISTRG mice.

Blood Adv 2020 Jun;4(11):2477-2488

Department of Medical Oncology and Hematology, University of Zurich and University Hospital Zurich, Zurich, Switzerland.

The engraftment potential of myeloproliferative neoplasms in immunodeficient mice is low. We hypothesized that the physiological expression of human cytokines (macrophage colony-stimulating factor, interleukin-3, granulocyte-macrophage colony-stimulating factor, and thrombopoietin) combined with human signal regulatory protein α expression in Rag2-/-Il2rγ-/- (MISTRG) mice might provide a supportive microenvironment for the development and maintenance of hematopoietic stem and progenitor cells (HSPC) from patients with primary, post-polycythemia or post-essential thrombocythemia myelofibrosis (MF). We show that MISTRG mice, in contrast to standard immunodeficient NOD. Read More

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http://dx.doi.org/10.1182/bloodadvances.2019001364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284099PMC

Thrombopoietin is required for full phenotype expression in a JAK2V617F transgenic mouse model of polycythemia vera.

PLoS One 2020 1;15(6):e0232801. Epub 2020 Jun 1.

Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.

The myeloproliferative neoplasms, polycythemia vera, essential thrombocytosis and primary myelofibrosis are hematopoietic stem cell disorders and share driver mutations that either directly activate the thrombopoietin receptor, MPL, or activate it indirectly through gain-of-function mutations in the gene for JAK2, its cognate tyrosine kinase. Paradoxically, MPL surface expression in hematopoietic stem cells is also reduced in the myeloproliferative neoplasms due to abnormal post-translational glycosylation and premature destruction of JAK2, suggesting that the myeloproliferative neoplasms are disorders of MPL processing since MPL is the only hematopoietic growth factor receptor in hematopoietic stem cells. To examine this possibility, we genetically manipulated MPL expression and maturation in a JAK2V617F transgenic mouse model of polycythemia vera. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232801PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263591PMC

The role of fedratinib for the treatment of patients with primary or secondary myelofibrosis.

Ther Adv Hematol 2020 15;11:2040620720925201. Epub 2020 May 15.

Division of Hematology and Oncology, UT Health San Antonio MD Anderson, Mail Code 8026, 6th Floor Urschel Tower, 7979 Wurzbach Rd, San Antonio, TX 78229-3900.

Myelofibrosis (MF) is a chronic myeloid neoplasm characterized by either primary myelofibrosis, or secondary MF following essential thrombocythemia or polycythemia vera. Historically, therapy has been symptom directed; however, in 2011, the first janus kinase inhibitor (JAK-i) - ruxolitinib - was approved for treatment. This medication was found to be effective in reduction of symptom burden and spleen size; however, the median duration of response is about 3 years. Read More

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http://dx.doi.org/10.1177/2040620720925201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232117PMC

Neoplastic fibrocytes play an essential role in bone marrow fibrosis in Jak2V617F-induced primary myelofibrosis mice.

Leukemia 2020 May 29. Epub 2020 May 29.

Department of Gastroenterology and Hematology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by clonal myeloproliferation, progressive bone marrow (BM) fibrosis, splenomegaly, and anemia. BM fibrosis was previously thought to be a reactive phenomenon induced by mesenchymal stromal cells that are stimulated by the overproduction of cytokines such as transforming growth factor (TGF)-β1. However, the involvement of neoplastic fibrocytes in BM fibrosis was recently reported. Read More

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http://dx.doi.org/10.1038/s41375-020-0880-3DOI Listing

Mutant specific anti calreticulin antibody (CAL2) immunohistochemistry as a screening test for calreticulin (CALR) mutation testing.

Int J Lab Hematol 2020 May 28. Epub 2020 May 28.

Department of Hematology, SGPGI, Lucknow, Uttar Pradesh, India.

Background: About 50 different CALR frameshift mutations have been identified in BCR-ABL1 negative MPN, all leading to the development of common new protein C terminus. Antibody targeting this terminal epitope can be useful to identify this driver mutation using immunohistochemistry.

Materials And Methods: CALR mutation analysis was carried out in 51 JAK2V617F negative cases, PMF (n = 22) and ET (n = 29). Read More

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http://dx.doi.org/10.1111/ijlh.13242DOI Listing
May 2020
1.870 Impact Factor

Secondary Pulmonary Alveolar Proteinosis Associated with Primary Myelofibrosis and Ruxolitinib Treatment: An Autopsy Case.

Intern Med 2020 May 23. Epub 2020 May 23.

Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.

Pulmonary alveolar proteinosis (PAP) is an uncommon lung disorder characterized by the excessive accumulation of surfactant-derived lipoproteins in the pulmonary alveoli and terminal bronchiole. Secondary PAP associated with primary myelofibrosis (PMF) is extremely rare, and to our knowledge, no autopsy case has been reported. We herein report an autopsy case of secondary PAP occurring in a patient with PMF who was treated with the Janus kinase 1/2 inhibitor ruxolitinib. Read More

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http://dx.doi.org/10.2169/internalmedicine.4082-19DOI Listing

Expansion of paroxysmal nocturnal hemoglobinuria clones in MPLW515L mutation harboring primary myelofibrosis.

Authors:
Keita Kirito

Ann Hematol 2020 May 23. Epub 2020 May 23.

Department of Hematology and Oncology, University of Yamanashi, 1110, Shimokato, Chuo-city, Yamanashi-ken, 409-3898, Japan.

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http://dx.doi.org/10.1007/s00277-020-04088-1DOI Listing

Myelofibrosis and Portal Hypertension: The Case for Primary Variceal Screening.

ACG Case Rep J 2020 Feb 2;7(2):e00333. Epub 2020 Mar 2.

Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

Myelofibrosis is a hematologic condition that predisposes to the formation of large and small portal venous clots. Portal injury is believed to underlie the mechanism of development of noncirrhotic portal hypertension in this population. We describe a patient with myelofibrosis, proven portal hypertension, and extramedullary hematopoiesis with no imaging or pathologic evidence of microvascular or macrovascular portal clot. Read More

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http://dx.doi.org/10.14309/crj.0000000000000333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209799PMC
February 2020

Optimizing the Conditioning Regimen for Hematopoietic Cell Transplant in Myelofibrosis: Long-Term Results of a Prospective Phase II Clinical Trial.

Biol Blood Marrow Transplant 2020 May 11. Epub 2020 May 11.

Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, Houston, Texas.

Optimal conditioning regimens for older patients with myelofibrosis undergoing allogeneic hematopoietic cell transplant are not known. Likewise, the role of dose intensity is not clear. We conducted a nonrandomized, prospective, phase II trial using low-dose, later escalated to high-dose (myeloablative conditioning), busulfan with fludarabine (Bu-Flu) in myelofibrosis patients up to age 74 years. Read More

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http://dx.doi.org/10.1016/j.bbmt.2020.03.020DOI Listing

Pulmonary hypertension in patients with Philadelphia-negative myeloproliferative neoplasms: a single-center retrospective analysis of 225 patients.

Blood Res 2020 Jun;55(2):77-84

Division of Hematology/Oncology, Department of Internal Medicine, College of Medicine, Chungnam National University, Daejeon, Korea.

Background: The prevalence of pulmonary hypertension (PH) in myeloproliferative neoplasms (MPNs) varies among studies. We analyzed the prevalence of PH in Korean patients with Philadelphia-negative (Ph-) MPNs.

Methods: Medical records of patients with Ph- MPNs [essential thrombocythemia (ET), polycythemia vera (PV), or primary myelofibrosis (PMF)] visiting a single hospital between 1993 and 2019 were reviewed retrospectively. Read More

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http://dx.doi.org/10.5045/br.2020.2020001DOI Listing

Systemic Mastocytosis with Associated Primary Myelofibrosis.

Indian J Hematol Blood Transfus 2020 Apr 28;36(2):442-443. Epub 2019 Oct 28.

2Dipartimento di Scienze Mediche e Sanità Pubblica, SC Ematologia e CTMO, Ospedale Businco, P.O. Businco, Università di Cagliari, Azienda Ospedaliera Brotzu, Via Jenner, sn, 09124 Cagliari, Italy.

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http://dx.doi.org/10.1007/s12288-019-01225-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229127PMC

Real-world risk assessment and treatment initiation among patients with myelofibrosis at community oncology practices in the United States.

Ann Hematol 2020 May 7. Epub 2020 May 7.

UT Health San Antonio Cancer Center, San Antonio, TX, USA.

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm with a prevalence of 4 to 6 per 100,000 people in the USA. Treatment recommendations are risk-adapted. This study was conducted to evaluate how physicians risk-stratify patients at the time of MF diagnosis, the accuracy of the risk stratification, and its effect on treatment selection. Read More

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http://dx.doi.org/10.1007/s00277-020-04055-wDOI Listing

Mutant Calreticulin in the Myeloproliferative Neoplasms.

Hemasphere 2020 Feb 15;4(1):e333. Epub 2020 Jan 15.

Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, United Kingdom and Department of Haematology, University of Cambridge.

Mutations in the gene for calreticulin () were identified in the myeloproliferative neoplasms (MPNs) essential thrombocythaemia (ET) and primary myelofibrosis (MF) in 2013; in combination with previously described mutations in and , driver mutations have now been described for the majority of MPN patients. In subsequent years, researchers have begun to unravel the mechanisms by which mutant CALR drives transformation and to understand their clinical implications. Mutant CALR activates the thrombopoietin receptor (MPL), causing constitutive activation of Janus kinase 2 (JAK2) signaling and cytokine independent growth in vitro. Read More

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http://dx.doi.org/10.1097/HS9.0000000000000333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000472PMC
February 2020

A Case of Primary Myelofibrosis in Which Ruxolitinib Therapy Ameliorated the Fibrosis, but Resulted in Fatty Marrow.

Gan To Kagaku Ryoho 2020 Feb;47(2):279-285

Dept. of Hematology, Juntendo University Urayasu Hospital.

A 63-year-old woman was referred to our department in 2015 because of anemia and thrombocytosis. MPL W515/K was positive, JAK-2V617F and CALR exon 9 were negative. Bone marrow(BM)biopsy led to a diagnosis of primary myelofibrosis (PMF)in the prefibrotic/early stage(Grade 1). Read More

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February 2020

A provider's guide to primary myelofibrosis: pathophysiology, diagnosis, and management.

Blood Rev 2020 Apr 7:100691. Epub 2020 Apr 7.

Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

Although understanding of the pathogenesis and molecular biology of primary myelofibrosis continues to improve, treatment options are limited, and several biological features remain unexplained. With an appropriate clinical history, exam, laboratory evaluation, and bone marrow biopsy, the diagnosis can often be established. Recent studies have better characterized prognostic factors and driver mutations in myelofibrosis, facilitated by use of next-generation sequencing. Read More

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http://dx.doi.org/10.1016/j.blre.2020.100691DOI Listing

Fedratinib in myelofibrosis.

Blood Adv 2020 Apr;4(8):1792-1800

Mays Cancer Center, UT Health San Antonio MD Anderson, San Antonio, TX.

Following the discovery of the JAK2V617F mutation in myeloproliferative neoplasms in 2005, fedratinib was developed as a small molecular inhibitor of JAK2. It was optimized to yield low-nanomolar activity against JAK2 (50% inhibitory concentration = 3 nM) and was identified to be selective for JAK2 relative to other JAK family members (eg, JAK1, JAK3, and TYK2). It quickly moved into clinical development with a phase 1 clinical trial opening in 2008, where a favorable impact on spleen and myelofibrosis (MF) symptom responses was reported. Read More

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http://dx.doi.org/10.1182/bloodadvances.2019000954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189288PMC

Ruxolitinib-based combinations in the treatment of myelofibrosis: worth looking forward to.

Ann Hematol 2020 Jun 24;99(6):1161-1176. Epub 2020 Apr 24.

Department of Hematology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.

Ruxolitinib is a targeted drug to treat myelofibrosis (MF). Ruxolitinib has significant advantages in spleen reduction and increasing 5-year overall survival (OS), and ruxolitinib-based combinations might provide more benefits than ruxolitinib monotherapy. In this review, we focus on the data of ruxolitinib-based combinations therapies and treatment-related adverse events (AEs) and safety. Read More

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http://dx.doi.org/10.1007/s00277-020-04028-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237512PMC

Immunoproteasome Genes Are Modulated in CD34 JAK2 Mutated Cells from Primary Myelofibrosis Patients.

Int J Mol Sci 2020 Apr 22;21(8). Epub 2020 Apr 22.

Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", University of Catania, 95125 Catania, Italy.

Primary myelofibrosis (PMF) is a rare myeloproliferative neoplasm characterized by stem-cell-derived clonal over-proliferation of mature myeloid lineages, bone marrow fibrosis, osteosclerosis, defective erythropoiesis, and pro-inflammatory cytokine over-expression. The aim of the present study was to highlight possible differences in the transcriptome among CD34 cells from peripheral blood (PB) of PMF patients. Therefore, we merged two microarray datasets of healthy control subjects and PMF (34 JAK2 MUTATED and 28 JAK2 wild-type). Read More

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http://dx.doi.org/10.3390/ijms21082926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216198PMC
April 2020
2.862 Impact Factor

STAT5 is Expressed in CD34/CD38 Stem Cells and Serves as a Potential Molecular Target in Ph-Negative Myeloproliferative Neoplasms.

Cancers (Basel) 2020 Apr 21;12(4). Epub 2020 Apr 21.

Ludwig Boltzmann Institute for Hematology and Oncology, Medical University of Vienna, 1090 Vienna, Austria.

Janus kinase 2 (JAK2) and signal transducer and activator of transcription-5 (STAT5) play a key role in the pathogenesis of myeloproliferative neoplasms (MPN). In most patients, V617F or mutations are found and lead to activation of various downstream signaling cascades and molecules, including STAT5. We examined the presence and distribution of phosphorylated (p) STAT5 in neoplastic cells in patients with MPN, including polycythemia vera (PV, = 10), essential thrombocythemia (ET, = 15) and primary myelofibrosis (PMF, = 9), and in the V617F-positive cell lines HEL and SET-2. Read More

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http://dx.doi.org/10.3390/cancers12041021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7225958PMC

A Prospective Pilot Study of Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide and Ruxolitinib in Patients with Myelofibrosis.

Acta Haematol 2020 Apr 23:1-8. Epub 2020 Apr 23.

R.M. Gorbacheva Memorial Institute of Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, Saint-Petersburg, Russian Federation.

Introduction: This prospective study evaluated a calcineurin inhibitor-free graft-versus-host disease (GVHD) prophylaxis regimen of ruxolitinib in combination with post-transplant cyclophosphamide (PTCy). Patents and Methods: Twenty patients with primary or secondary myelofibrosis were prospectively enrolled. Reduced intensity conditioning was performed, followed by allogeneic stem cell transplantation from related (n = 7) or unrelated (n = 13) donors. Read More

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http://dx.doi.org/10.1159/000506758DOI Listing

Infantile Myelofibrosis and Myeloproliferation with CDC42 Dysfunction.

J Clin Immunol 2020 May 17;40(4):554-566. Epub 2020 Apr 17.

Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Studies of genetic blood disorders have advanced our understanding of the intrinsic regulation of hematopoiesis. However, such genetic studies have only yielded limited insights into how interactions between hematopoietic cells and their microenvironment are regulated. Here, we describe two affected siblings with infantile myelofibrosis and myeloproliferation that share a common de novo mutation in the Rho GTPase CDC42 (Chr1:22417990:C>T, p. Read More

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http://dx.doi.org/10.1007/s10875-020-00778-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7253386PMC

Adhesion to fibronectin via α5β1 integrin supports expansion of the megakaryocyte lineage in primary myelofibrosis.

Blood 2020 Jun;135(25):2286-2291

Department of Medicine-Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA.

Excessive accumulation of extracellular matrix (ECM) is a hallmark of bone marrow (BM) milieu in primary myelofibrosis (PMF). Because cells have the ability to adhere to the surrounding ECM through integrin receptors, we examined the hypothesis that an abnormal ECM-integrin receptor axis contributes to BM megakaryocytosis in JAK2V617F+ PMF. Secretion of ECM protein fibronectin (FN) by BM stromal cells from PMF patients correlates with fibrosis and disease severity. Read More

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http://dx.doi.org/10.1182/blood.2019004230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316217PMC

Thrombotic Risk Detection in Patients with Polycythemia Vera: The Predictive Role of Mutations.

Cancers (Basel) 2020 Apr 10;12(4). Epub 2020 Apr 10.

Hematology Department, Hospital Universitario de Gran Canaria Dr. Negrín, 35019 Las Palmas de Gran Canaria, Spain.

The development of thrombotic events is common among patients with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). We studied the influence of pathogenic mutations frequently associated with myeloid malignancies on thrombotic events using next-generation sequencing (NGS) in an initial cohort of 68 patients with myeloproliferative neoplasms (MPN). As expected, the presence of mutations in and (DTA genes) was positively associated with age for the whole cohort ( = 0. Read More

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http://dx.doi.org/10.3390/cancers12040934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226609PMC

The use of Janus kinase inhibitors in the time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

J Am Acad Dermatol 2020 06 9;82(6):e223-e226. Epub 2020 Apr 9.

Department of Dermatology, Yale School of Medicine, New Haven, Connecticut. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.03.099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144601PMC

JAK2 exon 12 mutations in cases with JAK2V617F-negative polycythemia vera and primary myelofibrosis.

Ann Hematol 2020 May 10;99(5):983-989. Epub 2020 Apr 10.

Department of Hematology, Christian Medical College, Vellore, Tamil Nadu, India.

Molecular detection of JAK2 mutation (V617F or exon 12) is included as a major diagnostic criterion for polycythemia vera (PV) by the WHO 2016 guidelines. JAK2 exon 12 mutations are seen in about 2-5% of JAK2V617F-negative cases of PV. Mutations in JAK2 cause constitutive activation of JAK-STAT pathway which results in variable phenotypes. Read More

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http://dx.doi.org/10.1007/s00277-020-04004-7DOI Listing
May 2020
2.634 Impact Factor

Risk factors for progression to blast phase and outcome in 589 patients with myelofibrosis treated with ruxolitinib: Real-world data.

Hematol Oncol 2020 Apr 9. Epub 2020 Apr 9.

Department of Scienze Mediche, Chirurgiche e Tecnologie Avanzate "G.F. Ingrassia", University of Catania, Catania, Italy.

The impact of ruxolitinib therapy on evolution to blast phase (BP) in patients with myelofibrosis (MF) is still uncertain. In 589 MF patients treated with ruxolitinib, we investigated incidence and risk factors for BP and we described outcome according to disease characteristics and treatment strategy. After a median follow-up from ruxolitinib start of 3 years (range 0. Read More

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http://dx.doi.org/10.1002/hon.2737DOI Listing

The development of T-cell malignancies in patients with pre-existing myeloproliferative neoplasms: a report of three cases.

Ecancermedicalscience 2020 17;14:1011. Epub 2020 Feb 17.

Houston Methodist Cancer Center, 6445 Main Street, Outpatient Center, 24th Floor, Houston, TX 77030, USA.

Secondary acute myeloid leukaemia complicating the natural disease course of pre-existing Philadelphia chromosome-negative myeloproliferative neoplasms (PN-MPN) is well documented and associated with treatment challenges and significant morbidity. The incidence of a T-cell malignancy developing in patients with pre-existing PN-MPN is uncommon, with one case documented in the literature. We present two cases of angioimmunoblastic T-cell lymphoma (AITL) and one case of T-cell acute lymphoblastic leukaemia (T-ALL) that developed in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF), respectively. Read More

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http://dx.doi.org/10.3332/ecancer.2020.1011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105335PMC
February 2020

Effects of repeated oral doses of ketoconazole on a sequential ascending single oral dose of fedratinib in healthy subjects.

Cancer Chemother Pharmacol 2020 May 4;85(5):899-906. Epub 2020 Apr 4.

Bristol Myers Squibb, 556 Morris Ave, Summit, NJ, 07901, USA.

Purpose: Fedratinib is an orally administered Janus kinase 2-selective inhibitor that is indicated for the treatment of adult patients with intermediate-2 or high-risk myelofibrosis in the United States. Fedratinib is metabolized by multiple cytochrome P450s (CYPs) in vitro, with the predominant contribution from CYP3A4. The primary objective of this study was to evaluate the effects of 14-day repeated 200 mg twice daily (BID) oral doses of a strong CYP3A4 inhibitor, ketoconazole, on a sequential ascending single oral dose of fedratinib in healthy male subjects. Read More

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http://dx.doi.org/10.1007/s00280-020-04067-3DOI Listing

A case report of cryptococcal meningitis associated with ruxolitinib.

Medicine (Baltimore) 2020 Mar;99(13):e19587

Department of Neurology, Dokkyo Medical University, Mibu, Tochigi, Japan.

We herein report a 76-year-old Japanese man with myelofibrosis who developed cryptococcal meningitis. After treatment for 5 months with ruxolitinib, the patient presented with fever and disturbance of consciousness. Marked nuchal stiffness was noted. Read More

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http://dx.doi.org/10.1097/MD.0000000000019587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220082PMC

Increased incidence of infection in patients with myelofibrosis and transfusion-associated iron overload in the clinical setting.

Int J Hematol 2020 May 23;111(5):614-618. Epub 2020 Mar 23.

SC Ematologia e CTMO, Ospedale Businco, AOB, Dipartimento di Scienze Mediche e Sanità Pubblica, Università di Cagliari, Via Jenner, sn, 09124, Cagliari, Italy.

Transfusion-associated iron overload may lead to increased risk of infection, but its role in myelofibrosis (MF) has been scarcely explored. We evaluated 106 consecutive patients with primary or secondary MF. Up to 38% of patients were transfusion-dependent (TD) with a median of 14 RBC units received. Read More

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http://dx.doi.org/10.1007/s12185-020-02861-6DOI Listing

Reactivation of tuberculosis following ruxolitinib therapy for primary myelofibrosis: Case series and literature review.

Hematol Oncol Stem Cell Ther 2020 Mar 16. Epub 2020 Mar 16.

Division of Hematology and HSCT, Department of Oncology, King Abdul Aziz Medical City, Riyadh, Saudi Arabia; King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. Electronic address:

Primary myelofibrosis (PMF) is a subtype of BCR-ABL1 negative myeloproliferative neoplasm. Its characteristic features include clonal myeloproliferation, dysregulation of kinase signaling pathway, abnormal release of cytokines leading to fibrosis in the bone marrow, osteosclerosis, and extramedullary hematopoiesis. Approximately 20% of deaths occur because of disease progression, but death may also result occur because of cardiovascular complications or as a consequence of either infection or bleeding. Read More

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http://dx.doi.org/10.1016/j.hemonc.2020.02.003DOI Listing

Management of myelofibrosis after ruxolitinib failure.

Ann Hematol 2020 Jun 20;99(6):1177-1191. Epub 2020 Mar 20.

University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.

Myelofibrosis is a BCR-ABL1-negative myeloproliferative neoplasm characterized by anemia, progressive splenomegaly, extramedullary hematopoiesis, bone marrow fibrosis, constitutional symptoms, leukemic progression, and shortened survival. Constitutive activation of the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway, and other cellular pathways downstream, leads to myeloproliferation, proinflammatory cytokine expression, and bone marrow remodeling. Transplant is the only curative option for myelofibrosis, but high rates of morbidity and mortality limit eligibility. Read More

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http://dx.doi.org/10.1007/s00277-020-04002-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237516PMC