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Acta Clinica Belgica Apr 2015To date, only a small number of epidemiological studies on myelofibrosis have been performed. The current study aimed to characterize the myelofibrosis patient...
OBJECTIVE
To date, only a small number of epidemiological studies on myelofibrosis have been performed. The current study aimed to characterize the myelofibrosis patient population in Belgium according to pre-defined disease parameters (diagnosis, risk categories, hemoglobin <10 g/dl, spleen size, constitutional symptoms, platelet count, myeloblast count), with a view to obtaining a deeper understanding of the proportion of patients that may benefit from the novel myelofibrosis therapeutic strategies.
METHODS
A survey was used to collect data on prevalence and disease parameters on all myelofibrosis patients seen at each of 18 participating hematologic centers in 2011. Aggregated data from all centers were used for analysis. Analyses were descriptive and quantitative.
RESULTS
A total of 250 patients with myelofibrosis were captured; of these, 136 (54%) were male and 153 (61%) were over 65 years old. One hundred sixty-five (66%) of myelofibrosis patients had primary myelofibrosis and 85 (34%) had secondary myelofibrosis. One hundred ninety-three myelofibrosis patients (77%) had a palpable spleen. About a third of patients (34%) suffered from constitutional symptoms. Two hundred twenty-two (89%) myelofibrosis patients had platelet count ≧50 000/μl and 201 (80%) had platelet count ≧100 000/μl. Of 250 patients, 85 (34%) had a myeloblast count ≧1%. Six (2%) patients had undergone a splenectomy. Thirteen (5·2%) patients had undergone radiotherapy for splenomegaly.
CONCLUSIONS
The results of this survey provide insight into the characteristics of the Belgian myelofibrosis population. They also suggest that a large proportion of these patients could stand to benefit from the therapies currently under development.
Topics: Aged; Belgium; Cohort Studies; Female; Humans; Male; Middle Aged; Platelet Count; Prevalence; Primary Myelofibrosis
PubMed: 25380026
DOI: 10.1179/2295333714Y.0000000097 -
Hematology. American Society of... 2007Primary myelofibrosis (PMF) is a chronic myeloproliferative disorder associated with an average survival of less than 5 years. Therapy for PMF has used chemotherapeutic... (Review)
Review
Primary myelofibrosis (PMF) is a chronic myeloproliferative disorder associated with an average survival of less than 5 years. Therapy for PMF has used chemotherapeutic agents, immunomodulatory drugs, or biological-response modifiers that have not always been directed at the biological processes that underlie the origins of PMF. Such strategies are palliative and have an uncertain effect on survival. At present, allogeneic stem cell transplantation (ASCT) is the only means of altering the natural history of patients with PMF and provides the only hope for cure of this disorder. Enthusiasm for ASCT in PMF has been muted due to an unacceptable transplantation-related morbidity and mortality in patients receiving fully myeloablative conditioning regimens. Recently, a variety of reduced-intensity conditioning regimens have been utilized in older patients with PMF with significant comorbidities with promising results. Greater understanding of the cellular and molecular events that lead to the development of PMF have provided the opportunity for targeted therapies for PMF. Such therapies must be first evaluated in phase 1/2 trials using a variety of endpoints to assess their efficacy and their potential associated toxicities. The performance of randomized clinical trials comparing these agents to the present standard of care would permit for the first time evidence-based therapeutic decisions to be made for patients with PMF.
Topics: Antineoplastic Agents; Humans; Myeloablative Agonists; Primary Myelofibrosis; Prognosis; Stem Cell Transplantation; Transplantation Conditioning
PubMed: 18024650
DOI: 10.1182/asheducation-2007.1.346 -
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 -
European Journal of Haematology May 2009The clinical phenotype of myelofibrosis (MF) is recognized either de novo (primary) or in the setting of polycythemia vera (post-PV) or essential thrombocythemia... (Review)
Review
The clinical phenotype of myelofibrosis (MF) is recognized either de novo (primary) or in the setting of polycythemia vera (post-PV) or essential thrombocythemia (post-ET). Approximately one-third of patients with primary MF (PMF) present with cytogenetic abnormalities; the most frequent are del(20q), del(13q), trisomy 8 and 9, and abnormalities of chromosome 1 including duplication 1q. Other less frequent lesions include -7/del(7q), del(5q), del(12p), +21 and der(6)t(1;6)(q21;p21.3). In general, cytogenetic abnormalities are qualitatively similar among PMF, post-ET MF and post-PV MF although their individual frequencies may differ. Based on prognostic effect, cytogenetic findings in MF are classified as either 'favorable' or 'unfavorable'. The former include normal karyotype or isolated del(20q) or del(13q) and the latter all other abnormalities. Unfavorable cytogenetic profile in both PMF and post-PV/ET MF confers an independent adverse effect on survival; it is also associated with higher JAK2V617F mutational frequency. In addition to their prognostic value, cytogenetic studies in MF ensure diagnostic exclusion of other myeloid neoplasms that are sometimes associated with bone marrow fibrosis (e.g. BCR-ABL1-positive or PDGFRB-rearranged) and also assist in specific treatment selection (e.g. lenalidomide therapy is active in MF associated with del(5q).
Topics: Chromosome Aberrations; Cytogenetic Analysis; Diagnosis, Differential; Humans; Primary Myelofibrosis; Prognosis; Sequence Deletion
PubMed: 19141119
DOI: 10.1111/j.1600-0609.2009.01224.x -
Critical Reviews in Oncology/hematology 1990The purpose of this review is to discuss and clarify the current understanding of the pathogenesis, clinical manifestations, and treatment of MF. MF may be either a... (Review)
Review
The purpose of this review is to discuss and clarify the current understanding of the pathogenesis, clinical manifestations, and treatment of MF. MF may be either a primary or secondary disorder. It is characterized by an increased deposition of bone marrow collagen, fibronectin, and laminin. Present evidence indicates that MF may be mediated by platelet or megakaryocyte growth factors, decreased prostaglandin mediated stem cell inhibition, immune complex deposition, and both fibroblast and endothelial cell proliferation. Recently acute MF has been recognized to be identical to acute megakaryocytic leukemia. Secondary MF usually responds to appropriate treatment of the underlying disease. Primary MF is usually treated by blood product support, but may be responsive to androgens, splenectomy, splenic irradiation, chemotherapy, or bone marrow ablation with marrow reconstitution.
Topics: Combined Modality Therapy; Humans; Karyotyping; Primary Myelofibrosis; Prognosis
PubMed: 2278639
DOI: 10.1016/1040-8428(90)90007-f -
Hematological Oncology Jun 2006Idiopathic myelofibrosis (IMF) is the least common of the chronic myeloproliferative disorders and carries the worst prognosis with a median survival of 4 years. It is a... (Review)
Review
Idiopathic myelofibrosis (IMF) is the least common of the chronic myeloproliferative disorders and carries the worst prognosis with a median survival of 4 years. It is a clonal haematopoietic stem-cell disorder and, although the pathogenesis remains unclear, approximately 50% of cases are known to possess an activating JAK2 V617F mutation. In contrast, the characteristic stromal proliferation is a reactive, or secondary, event that results from the aberrant release of a variety of growth factors from megakaryocytes and monocytes. Treatment for most cases is supportive, although androgens, recombinant erythropoietin, steroids and thalidomide are effective modalities for the amelioration of anaemia. Myelosuppression, splenectomy and irradiation are valuable therapeutic modalities for specific clinical situations. Prognostic scores are available to aid the identification of cases for whom bone marrow transplantation should be considered. Recently, the use of reduced intensity conditioning has resulted in prolonged survival and lower transplant-related mortality. This review summarises the recent advances in the disease's pathogenesis and discusses the role of the various therapeutic options.
Topics: Anemia; Cytokines; Growth Hormone; Humans; Primary Myelofibrosis; Prognosis; Splenectomy
PubMed: 16477581
DOI: 10.1002/hon.771 -
Journal of Medical Case Reports Nov 2021Primary myelofibrosis is a rare myeloproliferative disorder in middle-aged and old adults and should be distinguished from secondary and reactive causes of bone marrow...
BACKGROUND
Primary myelofibrosis is a rare myeloproliferative disorder in middle-aged and old adults and should be distinguished from secondary and reactive causes of bone marrow fibrosis because, in reactive fibrosis, treatment approaches depend on the underlying etiology.
CASE PRESENTATION
Here we report the case of a middle-aged Iranian man who was diagnosed and treated as primary myelofibrosis at presentation, and whose final diagnosis was disseminated tuberculosis with reactive bone marrow fibrosis.
CONCLUSIONS
It is prudent to evaluate the potential causes of myelofibrosis in any patient with the diagnosis primary myelofibrosis. Tuberculosis can be an important etiology of bone marrow fibrosis, especially in endemic areas.
Topics: Adult; Humans; Iran; Male; Middle Aged; Primary Myelofibrosis; Tuberculosis
PubMed: 34749829
DOI: 10.1186/s13256-021-03038-3 -
American Journal of Hematology Nov 1988This paper reviews and clarifies the current understanding of the clinical and pathologic features and treatment of MF. Recent investigations indicate that MF may be... (Review)
Review
This paper reviews and clarifies the current understanding of the clinical and pathologic features and treatment of MF. Recent investigations indicate that MF may be mediated by platelet- and megakaryocyte-derived growth factors, impaired prostaglandin-mediated stem cell growth inhibition, or excessive endothelial cell and fibroblast proliferation. Immunologic disorders have been associated with MF. MF may be either a primary or a secondary phenomenon. Secondary MF often regresses with appropriate treatment of this underlying disorder. Primary MF may require androgen therapy, splenectomy, splenic irradiation, bone curettage, chemotherapy, or bone marrow transplantation.
Topics: Humans; Primary Myelofibrosis
PubMed: 3055953
DOI: 10.1002/ajh.2830290311 -
Journal of Clinical Oncology : Official... Sep 1999Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder characterized by bone marrow fibrosis and extramedullary hematopoiesis. Recent... (Review)
Review
PURPOSE
Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder characterized by bone marrow fibrosis and extramedullary hematopoiesis. Recent studies provide definite diagnostic criteria and prognostic classifications of the disease, and allogeneic stem-cell transplantation (SCT) now offers a chance of curing the disease. In order to put diagnostic criteria and prognostic classifications of the disease into the perspective of developing guidelines for treatment strategies, all studies published in the English literature over the last 30 years were reviewed.
MATERIALS AND METHODS
Studies were identified through a MEDLINE search (1966 to present) and from the bibliographies of relevant articles.
RESULTS
The Italian Consensus Conference on diagnostic criteria is a structured enterprise aimed at formulating a definition of MMM that will be used for enrolling patients onto clinical studies. It relies on the obligatory presence of myelofibrosis and on the exclusion of the BCR-ABL rearrangement or Philadelphia chromosome, in association with combinations of traditional features. Prognostic scores allow us to identify classes of patients on the basis of hemoglobin, age, WBC count, and chromosomal abnormalities. Several nonrandomized studies have indicated that allogeneic SCT for patients under the age of 55 is effective in prolonging survival in more than 50% of cases and in possibly curing the disease. Patients with the most severe prognosis are candidates.
CONCLUSION
"Consensus" methodology offers a definition of MMM useful for conducting and reporting clinical studies. A detailed knowledge of prognostic factors can help to delineate guidelines for addressing patients with allogeneic SCT.
Topics: Age Factors; Cell Division; Guidelines as Topic; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Megakaryocytes; Primary Myelofibrosis; Prognosis; Splenectomy
PubMed: 10561375
DOI: 10.1200/JCO.1999.17.9.2954 -
Best Practice & Research. Clinical... 2006Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (i.e. not yet molecularly defined) myeloproliferative disorder (MPD), along with... (Review)
Review
Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (i.e. not yet molecularly defined) myeloproliferative disorder (MPD), along with essential thrombocythemia (ET) and polycythemia vera (PV). All three MPDs represent stem-cell-derived clonal myeloproliferation that, in the case of MMM, is accompanied by an intense bone marrow stromal reaction that includes collagen fibrosis, osteosclerosis, and angiogenesis. To date, both the molecular basis of the primary clonal process and the pathogenetic mechanisms that underlie the secondary histological changes remain elusive. Clinically, MMM is characterized by anemia, multi-organ extramedullary hematopoiesis that often involves the spleen and liver, constitutional symptoms, and premature death from either leukemic transformation or other disease complications. Current diagnosis is based on characteristic but not diagnostic bone marrow histological features. Modern therapy remains palliative but allogeneic stem cell transplantation might be curative to a selected group of patients. This chapter reviews both the old and the new therapy with regard to non-transplant treatment options for MMM.
Topics: Combined Modality Therapy; Humans; Primary Myelofibrosis
PubMed: 16781486
DOI: 10.1016/j.beha.2005.07.008