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Haematologica Dec 2022
Topics: Humans; Leukemia, Megakaryoblastic, Acute; Primary Myelofibrosis; Megakaryocytes; Chronic Disease; Leukemia
PubMed: 35295083
DOI: 10.3324/haematol.2022.280838 -
Current Hematologic Malignancy Reports Dec 2017The purpose of the review was to provide a contemporary update of novel agents and targets under investigation in myelofibrosis in the Janus kinase (JAK) inhibitor era. (Review)
Review
PURPOSE OF REVIEW
The purpose of the review was to provide a contemporary update of novel agents and targets under investigation in myelofibrosis in the Janus kinase (JAK) inhibitor era.
RECENT FINDINGS
Myelofibrosis (MF) is a clonal stem cell disease characterized by marrow fibrosis and a heterogeneous disease phenotype with a variable degree of splenomegaly, cytopenias, and constitutional symptoms that significantly impact quality of life and survival. Overactive JAK/STAT signaling is a hallmark of MF. The only approved therapy for MF, JAK1/2 inhibitor ruxolitinib, can ameliorate splenomegaly, improve symptoms, and prolong survival in some patients. Therapeutic challenges remain, however. Myelosuppression limits the use of ruxolitinib in some patients, eventual drug resistance is common, and the underlying malignant clone persists despite therapy. A deeper understanding of the pathogenesis of MF has informed the development of additional agents. Promising targets under investigation include JAK1 and JAK2 and downstream intermediates in related signaling pathways, epigenetic modifiers, pro-inflammatory cytokines, and immune regulators.
Topics: Humans; Primary Myelofibrosis
PubMed: 29098608
DOI: 10.1007/s11899-017-0403-0 -
Journal of Clinical and Experimental... 2018In 2017, the revised World Health Organization was published. Regarding myeloproliferative neoplasms, histological findings of bone marrow biopsy is becoming more... (Review)
Review
In 2017, the revised World Health Organization was published. Regarding myeloproliferative neoplasms, histological findings of bone marrow biopsy is becoming more important for diagnosis. This article highlights particularly the morphology of megakaryocytes and evaluation of myelofibrosis for pathological diagnosis, and immunohistochemistry which can detect somatic mutation.
Topics: Biopsy; Bone Marrow; Histological Techniques; Humans; Megakaryocytes; Primary Myelofibrosis
PubMed: 29998975
DOI: 10.3960/jslrt.18006 -
American Journal of Hematology Jan 2010
Topics: Chromosome Aberrations; Disease-Free Survival; Humans; Patient Selection; Primary Myelofibrosis; Prognosis; Risk Factors; Severity of Illness Index; Stem Cell Transplantation
PubMed: 20029947
DOI: 10.1002/ajh.21586 -
American Journal of Hematology Dec 2018Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied...
DISEASE OVERVIEW
Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by stem cell-derived clonal myeloproliferation that is often but not always accompanied by JAK2, CALR, or MPL mutations; additional disease features include bone marrow stromal reaction including reticulin fibrosis, abnormal cytokine expression, anemia, hepatosplenomegaly, extramedullary hematopoiesis (EMH), constitutional symptoms, cachexia, leukemic progression, and shortened survival.
DIAGNOSIS
Diagnosis of PMF is based on bone marrow morphology. Presence of JAK2, CALR, or MPL mutation, expected in ∼ 90% of the patients, is supportive but not essential for diagnosis. The revised 2016 World Health Organization (WHO) classification system distinguishes "prefibrotic" from "overtly fibrotic" PMF; the former might mimic ET in its presentation and it is prognostically relevant to distinguish the two.
RISK STRATIFICATION
Two new prognostic systems for PMF have recently been introduced: GIPSS (genetically inspired prognostic scoring system) and MIPSS70+ version 2.0 (mutation- and karyotype-enhanced international prognostic scoring system). GIPSS is based exclusively on mutations and karyotype. MIPSS70+ version 2.0 utilizes both genetic and clinical risk factors. GIPSS features four and MIPSS70+ version 2.0 five risk categories. MIPSS70+ version 2.0 requires an online score calculator (http://www.mipss70score.it) while GIPPS offers a lower complexity prognostic tool.
RISK-ADAPTED THERAPY
Observation alone is advised for MIPSS70+ version 2.0 "low" and "very low" risk disease (estimated 10-year survival 56%-92%); allogeneic stem cell transplant is the preferred treatment of choice for "very high" and "high" risk disease (estimated 10-year survival 0-13%); treatment-requiring patients with intermediate-risk disease (estimated 10-year survival 30%) are best served by participating in clinical trials. All other treatment approaches, including the use of JAK2 inhibitors, are mostly palliative and should not be used in the absence of clear treatment indications. Conventional treatment for anemia includes androgens, prednisone, thalidomide and danazol, for symptomatic splenomegaly hydroxyurea and ruxolitinib and for constitutional symptoms ruxolitinib. Splenectomy is considered for drug-refractory splenomegaly and involved field radiotherapy for nonhepatosplenic EMH and extremity bone pain.
Topics: Disease Management; Humans; Karyotype; Mutation; Primary Myelofibrosis; Prognosis; Risk Assessment; Risk Factors; Therapeutics
PubMed: 30039550
DOI: 10.1002/ajh.25230 -
British Journal of Haematology Oct 2018The 2016 World Health Organization (WHO) classification for myeloproliferative neoplasms (MPN) divided myelofibrosis (MF) into pre-fibrotic (pre-MF) and overt-MF... (Review)
Review
The 2016 World Health Organization (WHO) classification for myeloproliferative neoplasms (MPN) divided myelofibrosis (MF) into pre-fibrotic (pre-MF) and overt-MF categories. This new classification, particularly the entity pre-MF, has been a subject of discussion between experts. Important questions have been raised in recent years, such as the need for bone marrow trephine for diagnosis; how this is interpreted and the weighting given to it in assigning a diagnosis; determination of prognosis for pre-MF patients; including which scoring system to use and, ultimately, an evidence-based management plan for this group of patients. Many pre-MF patients present as young adults, with thrombocytosis, elevated lactate dehydrogenase levels and increased bone marrow fibrosis (i.e. ≥ grade 1). Current management strategies differ in view of age, comorbidities and bone marrow features and the opinion of the managing clinicians. Prognostic scoring systems have some limitations regarding this entity, and at the present time there is limited information about the overall survival and incidence of progression to overt-MF and acute leukaemia for pre-MF. In this clinically focussed article, we review the main characteristics of this new disease category in view of the current published literature and illustrate our discussion with some real patient cases. Lastly, we propose a management strategy for patients to whom this diagnostic label is applied.
Topics: Disease Management; Fibrosis; Humans; Myeloproliferative Disorders; Primary Myelofibrosis; Prognosis; World Health Organization
PubMed: 30328618
DOI: 10.1111/bjh.15562 -
Annals of Hematology Apr 2023Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by mutations (most frequently in JAK2, CALR, or MPL), burdensome symptoms, splenomegaly, cytopenia, and... (Review)
Review
Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by mutations (most frequently in JAK2, CALR, or MPL), burdensome symptoms, splenomegaly, cytopenia, and shortened life expectancy. In addition to other clinical manifestations, patients with MF often develop anemia, which can either be directly related to MF pathogenesis or a result of MF treatment with Janus kinase (JAK) inhibitors, such as ruxolitinib and fedratinib. Although symptoms and clinical manifestations can be similar between the 2 anemia types, only MF-related anemia is prognostic of reduced survival. In this review, I detail treatment and patient management approaches for both types of anemia presentations and provide recommendations for the treatment of MF in the presence of anemia.
Topics: Humans; Primary Myelofibrosis; Janus Kinase 2; Splenomegaly; Nitriles; Anemia; Pyrrolidines; Sulfonamides
PubMed: 36786879
DOI: 10.1007/s00277-023-05126-4 -
Current Hematologic Malignancy Reports Oct 2022Philadelphia-negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), prefibrotic (pre-), and overt-primary... (Review)
Review
PURPOSE OF REVIEW
Philadelphia-negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), prefibrotic (pre-), and overt-primary myelofibrosis (primary MF, PMF). PV and ET could evolve into secondary MF (SMF), whose early diagnosis relies on monitoring signs of possible progression. All MPNs have a risk of blast phase (BP), that is associated with a very dismal outcome. Overall survival (OS) is different among MPNs, and disease-specific prognostic scores should be applied for a correct clinical management. In this review, an overview of current prognostic scores in MPNs will be provided.
RECENT FINDINGS
The biological complexity of MPNs and its role on the trajectory of disease outcome have led to the design of integrated prognostic models that are nowadays of common use in PMF patients. As for PV and ET, splicing gene mutations could have a detrimental role, but with the limit of the not routinary recommended application of extensive molecular analysis in these diseases. SMF is recognized as a distinct entity compared to PMF, and OS estimates should be calculated by the MYSEC-PM (Myelofibrosis SECondary-prognostic model). Both in PMF and SMF, decisions as selection of patients potentially candidates to allogenic stem cell transplant or that could benefit from an early shift from standard treatment are based not only on conventional prognostic scores, but also on multivariable algorithms. The expanding landscape of risk prediction for OS, evolution to BP, and SMF progression from PV/ET informs personalized approach to the management of patients affected by MPNs.
Topics: Humans; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Prognosis; Thrombocythemia, Essential
PubMed: 36048275
DOI: 10.1007/s11899-022-00672-6 -
Haematologica Jan 2011
Topics: Anemia; Erythrocyte Transfusion; Humans; Myelodysplastic Syndromes; Primary Myelofibrosis; Prognosis
PubMed: 21193428
DOI: 10.3324/haematol.2010.035519 -
American Journal of Hematology Sep 2022
Topics: Humans; Mutation; Phosphoproteins; Primary Myelofibrosis; Prognosis; RNA Splicing Factors
PubMed: 35796725
DOI: 10.1002/ajh.26648