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Clinical Lymphoma, Myeloma & Leukemia Sep 2020Splenomegaly, which may range from a few centimeters below the left costal border to massive dimensions, is one of the most characteristic features in patients with... (Review)
Review
Splenomegaly, which may range from a few centimeters below the left costal border to massive dimensions, is one of the most characteristic features in patients with advanced myelofibrosis (MF). Splenectomy may offer an effective therapeutic option for treating massive splenomegaly in patients with MF, and especially in cases of disease refractory to conventional drugs, but it is associated with a number of complications as well as substantial morbidity and mortality. Whether splenectomy should be performed before allogeneic hematopoietic stem-cell transplantation is also controversial, and there is a lack of prospective randomized clinical trials that assess the role of splenectomy before hematopoietic stem-cell transplantation in patients with MF. Although splenectomy is not routinely performed before transplantation, it may be appropriate in patients with massive splenomegaly and related symptoms, so long as the higher risk of graft failure in such cases is taken into account. This review aims to describe the efficacy, indications, and complications of splenectomy in patients with MF; and to evaluate the long-term impact of splenectomy on patient survival and risk of disease transformation.
Topics: Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Primary Myelofibrosis; Splenectomy; Transplantation Conditioning; Treatment Outcome
PubMed: 32482540
DOI: 10.1016/j.clml.2020.04.015 -
Haematologica Jan 2011
Topics: Anemia; Erythrocyte Transfusion; Humans; Myelodysplastic Syndromes; Primary Myelofibrosis; Prognosis
PubMed: 21193428
DOI: 10.3324/haematol.2010.035519 -
Archives of Disease in Childhood Nov 1980Two siblings developed a fulminant fatal myeloproliferative disease at 7 and 8 weeks of age. The illness presented with pallor, haemorrhagic symptoms, and...
Two siblings developed a fulminant fatal myeloproliferative disease at 7 and 8 weeks of age. The illness presented with pallor, haemorrhagic symptoms, and hepatosplenomegaly, and the blood picture was that of pancytopenia and leucoerythroblastosis. Bone marrow histology showed reduced haemopoiesis with generalised fibrosis. Histiocytes were present, but haemophagocytosis was not prominent. There was evidence of extramedullary haemopoiesis in the spleen, with a chronic inflammatory infiltrate of other organs. The condition closely resembles acute idiopathic myelofibrosis of infancy, but the early onset with severe pancytopenia and the histological appearances may arouse suspicion of the possible familial nature of the condition. Although clinically resembling familial haemophagocytic reticulosis, the uncharacteristic bone marrow, liver, and spleen histology serve to exclude this diagnosis.
Topics: Bone Marrow; Female; Humans; Infant; Male; Primary Myelofibrosis
PubMed: 7436463
DOI: 10.1136/adc.55.11.888 -
The Indian Journal of Tuberculosis Jul 2018Extramedullary hematopoisis (EMH) normally occurs in fetal life, but it is pathological in later life and most of the time because of underlying marrow diseases....
Extramedullary hematopoisis (EMH) normally occurs in fetal life, but it is pathological in later life and most of the time because of underlying marrow diseases. Sometimes EMH tissue can present with large masses which can cause compressive and constitutional symptoms. They can be wrongly diagnosed as malignancy and pulmonary tuberculosis. Here in this case report we are reporting a case with mediastinal EMH because of underlying mylofibrosis.
Topics: Biopsy; Diagnosis, Differential; Humans; Immunologic Factors; Lenalidomide; Male; Middle Aged; Primary Myelofibrosis; Tomography, X-Ray Computed; Tuberculosis, Pulmonary
PubMed: 29933872
DOI: 10.1016/j.ijtb.2017.06.014 -
Current Opinion in Hematology Mar 2015The myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia, and myelofibrosis. Of these, myelofibrosis often has the most aggressive course.... (Review)
Review
PURPOSE OF REVIEW
The myeloproliferative neoplasms include polycythemia vera, essential thrombocythemia, and myelofibrosis. Of these, myelofibrosis often has the most aggressive course. There is, however, often significant clinical heterogeneity among patients with myelofibrosis. We seek to summarize recent clinical and biological findings in myelofibrosis as well as review the spectrum of clinically relevant mutation in myelofibrosis and their implications.
RECENT FINDINGS
The mutational spectrum in myelofibrosis includes driver mutations in genes such as JAK2, calreticulin, and myeloproliferative leukemia virus oncogene. In addition, recurrent mutations in epigenetic modifiers such as ASXL1 and TET2 have also been described. Importantly, several studies have indicated that specific mutations, as well as the number of mutations, that a patient bears may have important clinical consequences. The presence or absence of certain mutations may help to determine a patient's risk for thrombosis, leukemic transformation, and survival.
SUMMARY
Myelofibrosis often has variable outcomes among patients. Prognostic systems based on clinical observations have been developed in an attempt to predict risks of disease progression and transformation. The discovery of recurrent genomic alterations in myelofibrosis, and the observation that many of these alterations may help predict clinical outcomes, has heralded a new era in the biologic understanding and clinical approach to myelofibrosis.
Topics: Genetic Predisposition to Disease; Humans; Mutation; Primary Myelofibrosis; Prognosis
PubMed: 25635755
DOI: 10.1097/MOH.0000000000000122 -
International Journal of Hematology Apr 2021Patients with primary myelofibrosis (PMF) have a poorer prognosis than those with other subtypes of myeloproliferative neoplasms (MPNs). To investigate the relationship...
Patients with primary myelofibrosis (PMF) have a poorer prognosis than those with other subtypes of myeloproliferative neoplasms (MPNs). To investigate the relationship between gene mutations and the prognosis of Japanese PMF patients, we analyzed mutations in 72 regions located in 14 MPN-relevant genes (CSF3R, MPL, JAK2, CALR, DNMT3A, TET2, EZH2, ASXL1, IDH1/2, SRSF2, SF3B1, U2AF1, and TP53) utilizing a target resequencing platform. In our cohort, ASXL1 mutations were more frequently detected in both overt and prefibrotic PMF patients than other mutations. The frequency of ASXL1 mutations was slightly higher among overt PMF patients than among prefibrotic PMF patients (44.6% vs 25.0%, FDR = 0.472). Decision tree classification algorithms revealed that ASXL1, EZH2, and SRSF2 mutations were associated with a poor prognosis for overt PMF. Overall survival was significantly shorter in patients harboring ASXL1, EZH2, or SRSF2 mutations than in those without these mutations (p = 0.03). These results suggest that, as reported in Western countries, MIPSS70 is applicable to Japanese PMF patients and ASXL1, EZH2, and SRSF2 mutations may be utilized as surrogate markers of a poor prognosis.
Topics: Alleles; Biomarkers; DNA Mutational Analysis; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; High-Throughput Nucleotide Sequencing; Humans; Japan; Kaplan-Meier Estimate; Mutation; Phenotype; Primary Myelofibrosis; Prognosis; Risk Assessment
PubMed: 33389584
DOI: 10.1007/s12185-020-03054-x -
Best Practice & Research. Clinical... Jun 2022Pre-Fibrotic Myelofibrosis is a frequently under-recognised entity that has distinct features separate to those of both Essential Thrombocythaemia and overt Primary... (Review)
Review
Pre-Fibrotic Myelofibrosis is a frequently under-recognised entity that has distinct features separate to those of both Essential Thrombocythaemia and overt Primary Myelofibrosis. Misdiagnosis is relatively common due to subtle differences in bone marrow trephine morphology and multidisciplinary approaches are required. The clinical phenotype and disease course is heterogeneous and hence management approaches tend to vary widely. Although patients may initially be asymptomatic, disease-related complications can include troublesome symptom burdens, increased incidence of both arterial and venous thromboses, haemorrhage, anaemia and an inherent risk of disease evolution to either overt myelofibrosis or blastic phase disease. Specific prognostic tools with high discriminatory power are lacking. Within this review we use case-based approaches to review the current literature, highlight challenges in both diagnostics and disease management and suggest contemporary approaches to improve patient outcomes.
Topics: Humans; Primary Myelofibrosis; Thrombocythemia, Essential; Bone Marrow; Prognosis; Disease Progression
PubMed: 36333067
DOI: 10.1016/j.beha.2022.101378 -
Hematology/oncology Clinics of North... Oct 2003MMM is a chronic myeloproliferative disorder characterized by bone marrow fibrosis and neoangiogenesis, constitutive release ofa high number of CD34+ stem cells from the... (Review)
Review
MMM is a chronic myeloproliferative disorder characterized by bone marrow fibrosis and neoangiogenesis, constitutive release ofa high number of CD34+ stem cells from the bone marrow, and extramedullary hematopoiesis. It presents with heterogeneous clinical features in which anemia and progression to symptomatic splenomegaly dominate. The pathogenesis is undefined, but the dual action of deregulation of the bFGF pathway may influence myeloproliferation, myelofibrosis, and neoangiogenesis. Animal models suggest that chronic exposure to high doses of thrombopoietin or impairment of the capacity of megakaryocytes to differentiate into platelets, as occurs in the GATA-1(low) mice, is a necessary event for myelofibrosis. Allogeneic stem cell transplantation offers a chance of cure, and low conditioning regimens may extend the age of transplantable patients with lower mortality. Autologus stem cell transplantation and splenectomy are risky procedures that may be considered in patients with advanced disease when conventional therapies for correcting anemia (danazol, recombinant human erythropoietin, or cyclosporine) or chemotherapy for splenomegaly and myeloproliferation (hydroxyurea or interferon alfa) have failed. Thalidomide has been tested in numerous series, and its capacity to improve anemia and thrombocytopenia while reducing splenomegaly has been documented.
Topics: Diagnosis, Differential; Humans; Incidence; Primary Myelofibrosis
PubMed: 14560783
DOI: 10.1016/s0889-8588(03)00080-7 -
The New England Journal of Medicine Apr 2000
Review
Topics: Antineoplastic Agents; Bone Marrow; Diagnosis, Differential; Hematopoietic Stem Cell Transplantation; Humans; Hydroxyurea; Primary Myelofibrosis; Prognosis; Splenectomy; Suramin
PubMed: 10781623
DOI: 10.1056/NEJM200004273421706 -
Neurology India 2017
Topics: Adult; Brain; Hematopoiesis, Extramedullary; Humans; Magnetic Resonance Imaging; Male; Primary Myelofibrosis
PubMed: 28681787
DOI: 10.4103/neuroindia.NI_1151_16