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Blood Cancer Journal Jul 2023
Topics: Humans; Primary Myelofibrosis; Thrombocythemia, Essential; Motivation; Thrombosis; Bone Marrow
PubMed: 37507408
DOI: 10.1038/s41408-023-00887-7 -
British Journal of Haematology Nov 2022Myeloproliferative neoplasms can be associated with bleeding manifestations which can cause significant morbidities. Although haematologists are aware of the likelihood... (Review)
Review
Myeloproliferative neoplasms can be associated with bleeding manifestations which can cause significant morbidities. Although haematologists are aware of the likelihood of this complication in the setting of myeloproliferative neoplasms, it may often be overlooked especially in patients with no extreme elevation of blood counts and those with myelofibrosis. Acquired von Willebrand syndrome and platelet dysfunction are the two common diagnoses to be considered in this regard. In this review article, we discuss the mechanisms for the development of these rare bleeding disorders, their diagnosis and practical management.
Topics: Humans; von Willebrand Factor; Neoplasms; Myeloproliferative Disorders; von Willebrand Diseases; Primary Myelofibrosis; Hemorrhage
PubMed: 35724983
DOI: 10.1111/bjh.18322 -
Biology of Blood and Marrow... Apr 2018The prognosis of myeloproliferative neoplasms, including primary myelofibrosis (PMF), polycythemia vera, and essential thrombocythemia varies considerably, between these... (Review)
Review
The prognosis of myeloproliferative neoplasms, including primary myelofibrosis (PMF), polycythemia vera, and essential thrombocythemia varies considerably, between these disorders as well as within each diagnosis. Molecular studies have identified "driver mutations" in JAK2, MPL1, and CALR and additional somatic DNA mutations, including ASXL1, EZH2, IDH1/2, and SRSF2, that affect prognosis differentially. Patients with mutations in CALR (type1) have a better outlook than patients with mutations in JAK2 or MPL, whereas patients without any of the driver mutations (triple negative) have the shortest life expectancy. Mutations in ASXL1, EZH2, and SRSF2 may be associated with shortened survival, and IDH mutations carry a higher risk of leukemic transformation. The combination and number of mutations are more important than a given single mutation. Mutations also appear to impact the outcome of hematopoietic cell transplantation (HCT), currently the only treatment with curative potential. Based on available data, the best post-HCT outcome is observed with CALR mutations. Triple negativity has a negative impact. The data on JAK2 are controversial. Mutations in ASXL1 or IDH1/2 reduce the probability of progression-free survival after HCT, although the impact of ASXL1 differs between patients with primary and secondary myelofibrosis. Although it is not clear to what extent HCT can overcome the risks associated with a given mutational pattern, at present, early HCT should be considered in triple-negative patients and patients with PMF who harbor mutations in ASXL1. Mutations in EZH2, SRSF2, or IDH, particularly if combined with other mutations, should also lead to consideration of HCT. Further studies are needed to validate the present observations and determine the impact of additional mutations that have been identified.
Topics: Allografts; Decision Making; Disease-Free Survival; Hematopoietic Stem Cell Transplantation; Humans; Mutation; Neoplasm Proteins; Primary Myelofibrosis; Survival Rate
PubMed: 29128551
DOI: 10.1016/j.bbmt.2017.10.037 -
Frontiers in Immunology 2021Myeloid neoplasms, including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), and myelodysplastic syndromes (MDS), feature clonal dominance and... (Review)
Review
Myeloid neoplasms, including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), and myelodysplastic syndromes (MDS), feature clonal dominance and remodeling of the bone marrow niche in a manner that promotes malignant over non-malignant hematopoiesis. This take-over of hematopoiesis by the malignant clone is hypothesized to include hyperactivation of inflammatory signaling and overproduction of inflammatory cytokines. In the -negative MPNs, inflammatory cytokines are considered to be responsible for a highly deleterious pathophysiologic process: the phenotypic transformation of polycythemia vera (PV) or essential thrombocythemia (ET) to secondary myelofibrosis (MF), and the equivalent emergence of primary myelofibrosis (PMF). Bone marrow fibrosis itself is thought to be mediated heavily by the cytokine TGF-β, and possibly other cytokines produced as a result of hyperactivated JAK2 kinase in the malignant clone. MF also features extramedullary hematopoiesis and progression to bone marrow failure, both of which may be mediated in part by responses to cytokines. In MF, elevated levels of individual cytokines in plasma are adverse prognostic indicators: elevated IL-8/CXCL8, in particular, predicts risk of transformation of MF to secondary AML (sAML). Tumor necrosis factor (TNF, also known as TNFα), may underlie malignant clonal dominance, based on results from mouse models. Human PV and ET, as well as MF, harbor overproduction of multiple cytokines, above what is observed in normal aging, which can lead to cellular signaling abnormalities separate from those directly mediated by hyperactivated JAK2 or MPL kinases. Evidence that NFκB pathway signaling is frequently hyperactivated in a pan-hematopoietic pattern in MPNs, including in cells outside the malignant clone, emphasizes that MPNs are pan-hematopoietic diseases, which remodel the bone marrow milieu to favor persistence of the malignancy. Clinical evidence that JAK2 inhibition by ruxolitinib in MF neither reliably reduces malignant clonal burden nor eliminates cytokine elevations, suggests targeting cytokine mediated signaling as a therapeutic strategy, which is being pursued in new clinical trials. Greater knowledge of inflammatory pathophysiology in MPNs can therefore contribute to the development of more effective therapy.
Topics: Age Factors; Biomarkers; Cell Transformation, Neoplastic; Cytokines; Disease Susceptibility; Humans; Inflammation Mediators; Models, Biological; Myeloproliferative Disorders; Primary Myelofibrosis; Signal Transduction
PubMed: 34140953
DOI: 10.3389/fimmu.2021.683401 -
Cells Feb 2022Moving from indication to transplantation is a critical process in myelofibrosis. Most of guidelines specifically focus on either myelofibrosis disease or transplant... (Review)
Review
Moving from indication to transplantation is a critical process in myelofibrosis. Most of guidelines specifically focus on either myelofibrosis disease or transplant procedure, and, currently, no distinct indication for the management of MF candidates to transplant is available. Nevertheless, this period of time is crucial for the transplant outcome because engraftment, non-relapse mortality, and relapse incidence are greatly dependent upon the pre-transplant management. Based on these premises, in this review, we will go through the path of identification of the MF patients suitable for a transplant, by using disease-specific prognostic scores, and the evaluation of eligibility for a transplant, based on performance, comorbidity, and other combined tools. Then, we will focus on the process of donor and conditioning regimens' choice. The pre-transplant management of splenomegaly and constitutional symptoms, cytopenias, iron overload and transplant timing will be comprehensively discussed. The principal aim of this review is, therefore, to give a practical guidance for managing MF patients who are potential candidates for allo-HCT.
Topics: Aged; Aged, 80 and over; Hematopoietic Stem Cell Transplantation; Humans; Primary Myelofibrosis; Transplantation Conditioning; Transplantation, Homologous
PubMed: 35159362
DOI: 10.3390/cells11030553 -
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 -
British Journal of Haematology Mar 2005The conventional treatment of myelofibrosis involves a wait-and-see approach for asymptomatic patients, oral chemotherapy for the hyperproliferative forms of the... (Review)
Review
The conventional treatment of myelofibrosis involves a wait-and-see approach for asymptomatic patients, oral chemotherapy for the hyperproliferative forms of the disease, androgens or erythropoietin for the anaemia, and splenectomy in selected patients. Low-dose thalidomide plus prednisone is a well-tolerated therapy for the anaemia and the thrombocytopenia of myelofibrosis, whereas imatinib has shown little efficacy. Allogeneic stem cell transplantation (allo-SCT) is the only curative therapy for myelofibrosis. Its standard modality has an associated mortality of about 30% and can be applied to younger patients with high-risk disease or resistant to conventional treatment. Reduced-intensity conditioning allo-SCT involves a low mortality and is a promising therapy for patients aged 45-70 years old with the above characteristics. Autologous SCT is a palliative therapy for patients resistant to conventional treatment who lack a suitable donor. The next candidates for the treatment of myelofibrosis are the thalidomide derivatives, the proteasome inhibitors, and vascular endothelial growth factor neutralizing antibodies.
Topics: Adult; Angiogenesis Inhibitors; Anti-Inflammatory Agents; Humans; Middle Aged; Palliative Care; Prednisone; Primary Myelofibrosis; Splenectomy; Stem Cell Transplantation; Thalidomide; Transplantation, Autologous; Transplantation, Homologous
PubMed: 15725078
DOI: 10.1111/j.1365-2141.2004.05301.x -
Haematologica Jan 2011
Topics: Anemia; Erythrocyte Transfusion; Humans; Myelodysplastic Syndromes; Primary Myelofibrosis; Prognosis
PubMed: 21193428
DOI: 10.3324/haematol.2010.035519 -
Current Hematologic Malignancy Reports Jun 2024Summarize best practices for management of patients with early myelofibrosis (MF). (Review)
Review
PURPOSE OF REVIEW
Summarize best practices for management of patients with early myelofibrosis (MF).
RECENT FINDINGS
Myelofibrosis is a progressive myeloproliferative neoplasm (MPN) that generally produces burdensome symptoms and ultimately leads to worse overall survival than that observed in healthy controls or patients with other MPNs. Several Janus kinase inhibitors and various interferon formulations are now available for treatment of MF, with ruxolitinib notable for extending overall survival in addition to improving MF signs and symptoms. The chronic nature of the disease can lead some patients to avoid immediate treatment in favor of a watch-and-wait approach. This review summarizes the patient management approach taken in my practice, providing guidance and a discussion of best practices with an emphasis on the importance and clinical benefits of active treatment in early MF. In particular, a case is made to consider treatment with ruxolitinib for patients with intermediate-1 risk disease and to minimize delay between diagnosis and treatment initiation for patients with intermediate or high-risk disease.
Topics: Humans; Primary Myelofibrosis; Disease Management; Pyrazoles; Pyrimidines; Nitriles; Janus Kinase Inhibitors; Practice Guidelines as Topic
PubMed: 38441783
DOI: 10.1007/s11899-024-00729-8 -
Turkish Journal of Haematology :... Feb 2020
Topics: Aged, 80 and over; Antineoplastic Agents; Humans; Hydroxyurea; Male; Primary Myelofibrosis; Tooth Discoloration
PubMed: 31711282
DOI: 10.4274/tjh.galenos.2019.2019.0275