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Haematologica Jan 2014
Topics: Female; Humans; Male; Primary Myelofibrosis
PubMed: 24425686
DOI: 10.3324/haematol.2013.101279 -
Journal of Clinical Immunology Jul 2023
Review
Topics: Humans; Primary Myelofibrosis; Hematopoietic Stem Cell Transplantation; Neutropenia; Congenital Bone Marrow Failure Syndromes; Transplantation Conditioning; Vesicular Transport Proteins
PubMed: 36913133
DOI: 10.1007/s10875-023-01467-x -
Expert Review of Hematology Jul 2018The 2016 WHO classification comprises two stages of primary myelofibrosis (PMF): early/prefibrotic primary myelofibrosis (pre-PMF) and overt fibrotic PMF (overt PMF).... (Review)
Review
The 2016 WHO classification comprises two stages of primary myelofibrosis (PMF): early/prefibrotic primary myelofibrosis (pre-PMF) and overt fibrotic PMF (overt PMF). Diagnostic criteria rely on bone marrow morphology, fibrosis grade (0-1 in pre-PMF, 2-3 in overt PMF), and clinical features (leukoerythroblastosis, anemia, leucocytosis, increased lactate dehydrogenase, and palpable splenomegaly). An accurate differentiation from essential thrombocythemia (ET) is pivotal because the two entities show different clinical presentation and outcome, in terms of survival, leukemic evolution, and rates of progression to overt myelofibrosis. Areas covered: The current review provides an overview on how to diagnose and stratify patients with pre-PMF, taking into account their definite and peculiar risk of vascular event, which is often neglected, and their milder disease course, compared with overt PMF, with the aim of improving and individualizing their counseling and management. Expert commentary: Pre-PMF is a new entity characterized by a unique combination of both a thrombo-hemorrhagic risk (that brings it closer to PV and ET) and a definite risk of disease evolution (that places pre-PMF somewhat closer to the overt PMF variant).
Topics: Humans; Precision Medicine; Primary Myelofibrosis
PubMed: 29862872
DOI: 10.1080/17474086.2018.1484280 -
Acta Bio-medica : Atenei Parmensis Jan 2022Philadelphia negative myeloproliferative neoplasms (MPNs) are classically characterized by excess production of terminal myeloid cells in the peripheral blood. They...
Philadelphia negative myeloproliferative neoplasms (MPNs) are classically characterized by excess production of terminal myeloid cells in the peripheral blood. They include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Among this group, primary myelofibrosis is the least common and usually carries the worst prognosis. Bone involvement in primary myelofibrosis has many forms; it affects bone marrow leading to bone marrow fibrosis, it can cause periostitis, in addition to bone and joint pain. A common radiologic finding in primary myelofibrosis is the presence of osteosclerotic lesions. However, the presence of osteolytic lesions in bone imaging was described in few reports. In this review, we searched English literature using the PRISMA guidelines looking for patients with Primary myelofibrosis who had osteolytic bone lesions to assess the impact of such findings on the disease and its effect on prognosis. We found the vast majority of lesions were painful affecting most commonly the vertebral column, pelvis, and ribs, and were detected in patients above 50 years of age with no gender preference, unfortunately they represented advanced disease stages, resulting in inadequate treatment response and poor outcome.
Topics: Bone Marrow; Humans; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Thrombocythemia, Essential
PubMed: 35075062
DOI: 10.23750/abm.v92i6.12350 -
Current Hematologic Malignancy Reports Mar 2012Primary myelofibrosis (PMF) is a Philadelphia chromosome-negative chronic myeloproliferative neoplasm usually affecting elderly people. Median survival currently...
Primary myelofibrosis (PMF) is a Philadelphia chromosome-negative chronic myeloproliferative neoplasm usually affecting elderly people. Median survival currently approaches 6 years, with a few patients surviving more than 20 years but others dying soon after diagnosis. In 10% to 20% of patients, PMF evolves into acute leukemia. Conventional treatment is merely palliative and does not prolong survival. The only chance for cure is allogeneic hemopoietic stem-cell transplantation (allo-HSCT), which is associated with high morbidity and mortality. Introduction of less aggressive forms of allo-HSCT and the prospect of molecular-targeted therapies has renewed interest in prognostication in PMF. The most important prognostic factors are anemia, age over 65 years, constitutional symptoms, leukocytosis, blood blasts, and some cytogenetic abnormalities. These factors have recently been systematized into an International Prognostic Scoring System (IPSS) and further refined in a dynamic IPSS (DIPSS), useful at any time over the disease course, as well as a DIPSS-plus model including karyotypic information.
Topics: Age Factors; Anemia; Cell Transformation, Neoplastic; Cytogenetics; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Platelet Count; Primary Myelofibrosis; Prognosis; Risk Assessment
PubMed: 22072485
DOI: 10.1007/s11899-011-0102-1 -
BMC Cancer Jan 2023Primary myelofibrosis [PMF] is a myeloproliferative neoplasm associated with reduced overall survival (OS). Management strategies for PMF have evolved over the last two...
BACKGROUND
Primary myelofibrosis [PMF] is a myeloproliferative neoplasm associated with reduced overall survival (OS). Management strategies for PMF have evolved over the last two decades, including approval of ruxolitinib as the first Janus kinase 1 (JAK1)/JAK2 inhibitor for patients with intermediate or high-risk myelofibrosis. This study assessed changes in mortality before and after ruxolitinib approval, independent of ruxolitinib treatment.
METHODS
This retrospective study investigated mortality trends among US veterans with PMF in 2 time periods, pre-ruxolitinib approval (01/01/2007-12/31/2010) and post-ruxolitinib approval (01/01/2015-09/30/2018). Deidentified patient-level data were extracted from US Veterans Health Administration (VHA) databases using PMF diagnosis codes; index was the first PMF diagnosis date. The analysis included adults with ≥2 PMF claims during the analysis periods who were continuously enrolled in the VHA plan 1 calendar year prior to and 6 months post-index and had ≥1 available International Prognostic Scoring System (IPSS) risk factor (available factors were age > 65, hemoglobin < 10 g/dL, and white blood cell count > 25 × 10/L; each counted as one point). Patients with ≥1 MF diagnosis for 12 months before the index period were excluded. Ruxolitinib treatment was not a requirement to be included in the post-ruxolitinib approval cohort. Mortality rates and OS were estimated using the Kaplan-Meier approach; all-cause mortality hazard ratio was estimated using univariate Cox regression.
RESULTS
The pre- and post-ruxolitinib approval cohorts included 193 and 974 patients, respectively, of which 80 and 197 had ≥2 IPSS risk factors. Ruxolitinib use in the post-ruxolitinib cohort was 8.5% (83/974). At end of follow-up, median (95% CI) OS was significantly shorter in the pre-ruxolitinib cohort (1.7 [1.2-2.6] years vs not reached [3.4-not reached]; P < 0.001). Overall mortality rates for the pre- versus post-ruxolitinib approval cohorts were 79.8% versus 47.3%, respectively, and overall risk of death was 53% lower in the post-ruxolitinib period (hazard ratio, 0.47; 95% CI, 0.37-0.58; P < 0.001). Mortality rates were lower among patients with < 2 vs ≥2 IPSS risk factors.
CONCLUSIONS
Although veterans with PMF have high overall mortality rates, and results in this population might not be generalizable to the overall population, there was a significant lowering of mortality rate in the post-ruxolitinib period.
Topics: Adult; Humans; Nitriles; Primary Myelofibrosis; Pyrazoles; Retrospective Studies; Veterans; United States
PubMed: 36641455
DOI: 10.1186/s12885-022-10495-6 -
Magyar Onkologia Mar 2017Primary myelofibrosis (PMF) is a Philadelphia chromosome negative, clonal myeloproliferative neoplasm characterised by a progressive nature. Morphologically, the bone... (Review)
Review
Primary myelofibrosis (PMF) is a Philadelphia chromosome negative, clonal myeloproliferative neoplasm characterised by a progressive nature. Morphologically, the bone marrow biopsy shows features of abnormal proliferation of terminally differentiated megakaryocytes and subsequent bone marrow fibrosis. The molecular landscape of PMF includes phenotypic driver mutations (JAK2 V617F, CALR and MPL) which represent major diagnostic criteria, and subclonal mutations that also occur in several other myeloid diseases, but have a prognostic value in disease progression of MF. The most important subclonal mutations affect the genes ASXL1, TET2, IDH1/2, EZH2 and TP53. Triple negative genotype and the high molecular risk genotype and CALR-/ASXL1+ are associated with adverse survival with the latest indicating stem cell transplantation independently of the DIPSS-plus score.
Topics: Bone Marrow; Humans; Mutation; Primary Myelofibrosis; Prognosis
PubMed: 28273187
DOI: No ID Found -
Hematology (Amsterdam, Netherlands) Mar 2014
Topics: Humans; Primary Myelofibrosis
PubMed: 24611775
DOI: 10.1179/1024533213Z.000000000257 -
BMJ (Clinical Research Ed.) Feb 1997
Review
Topics: Humans; Polycythemia; Primary Myelofibrosis; Thrombocytosis
PubMed: 9055722
DOI: 10.1136/bmj.314.7080.587 -
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