The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Joseph H Butterfield - One of the best experts on this subject based on the ideXlab platform.
-
Primary headache syndromes in Systemic Mastocytosis.
Cephalalgia : an international journal of headache, 2011Co-Authors: Jonathan H. Smith, Joseph H Butterfield, F. Michael CutrerAbstract:Aim: To investigate the relationship between clinical mast cell activity and primary headache syndromes.Methods: We surveyed individuals with Systemic Mastocytosis, an uncommon disorder associated ...
-
increased leukotriene e4 excretion in Systemic Mastocytosis
Prostaglandins & Other Lipid Mediators, 2010Co-Authors: Joseph H ButterfieldAbstract:Abstract Cysteinyl leukotrienes such as LTE4 are produced by mast cells, neutrophils, eosinophils, and macrophages. LTE4 levels have not been reported in Systemic Mastocytosis, a disorder with a large increase in mast cell numbers. Urinary LTE4 from patients referred for symptoms potentially due to mast cell degranulation or Systemic Mastocytosis was measured by a commercial cysteinyl leukotriene enzyme immunoassay kit. The diagnosis of Systemic Mastocytosis was established using current World Health Organization criteria. Compared with a control group of patients with various potential mast cell–related symptoms (e.g., “spells”), patients with Systemic Mastocytosis had a significant (P = .01) increase in urinary LTE4 excretion, whether expressed as LTE4 ng/g creatinine or as LTE4 ng/24 h. There was a moderate correlation of LTE4 ng/24 h with excretion of N-methyl histamine and serum tryptase but not with urinary 11β-prostaglandin F2α (11β-PGF2α) excretion. LTE4 excretion is increased in patients with Systemic Mastocytosis and potentially contributes to clinical symptoms.
-
Increased leukotriene E4 excretion in Systemic Mastocytosis.
Prostaglandins & other lipid mediators, 2010Co-Authors: Joseph H ButterfieldAbstract:Cysteinyl leukotrienes such as LTE(4) are produced by mast cells, neutrophils, eosinophils, and macrophages. LTE(4) levels have not been reported in Systemic Mastocytosis, a disorder with a large increase in mast cell numbers. Urinary LTE(4) from patients referred for symptoms potentially due to mast cell degranulation or Systemic Mastocytosis was measured by a commercial cysteinyl leukotriene enzyme immunoassay kit. The diagnosis of Systemic Mastocytosis was established using current World Health Organization criteria. Compared with a control group of patients with various potential mast cell-related symptoms (e.g., "spells"), patients with Systemic Mastocytosis had a significant (P=.01) increase in urinary LTE(4) excretion, whether expressed as LTE(4) ng/g creatinine or as LTE(4) ng/24h. There was a moderate correlation of LTE(4) ng/24h with excretion of N-methyl histamine and serum tryptase but not with urinary 11beta-prostaglandin F(2alpha) (11beta-PGF(2alpha)) excretion. LTE(4) excretion is increased in patients with Systemic Mastocytosis and potentially contributes to clinical symptoms.
-
Survey of Aspirin Administration in Systemic Mastocytosis
Journal of Allergy and Clinical Immunology, 2009Co-Authors: Joseph H ButterfieldAbstract:Abstract Background Previous recommended doses for aspirin use in Systemic Mastocytosis have been 3.9–5.2 g/d. Here, the aspirin doses and biochemical responses of patients with Systemic Mastocytosis given aspirin to decrease prostaglandin D2 levels and prevent symptoms were reviewed. Methods Twenty patients with Systemic Mastocytosis who had been given aspirin were identified, and their clinical and laboratory records were reviewed including changes in the excretion of the prostaglandin D2 metabolite 11β-prostaglandin F2α in response to aspirin. Results Two of 20 patients developed either a delayed reaction or flushing during outpatient updosing with aspirin. In 20 of 20 patients with elevated baseline urinary excretion of 11β-prostaglandin F2α, aspirin therapy caused a reduction to normal levels of excretion. Doses of aspirin required ranged from 81 mg twice daily to 500 mg twice daily. Conclusions Control of elevated prostaglandin D2 levels in Systemic Mastocytosis can be achieved with lower doses of aspirin than previously reported as necessary in this disorder.
Edward J. Fox - One of the best experts on this subject based on the ideXlab platform.
-
Pathologic long bone fracture in a patient with Systemic Mastocytosis
Clinical Orthopaedics and Related Research, 2007Co-Authors: Joseph J. King, Eileen A. Crawford, O. Hans Iwenofu, Edward J. FoxAbstract:Systemic Mastocytosis is characterized by clonal proliferation of mast cells, which cause disease by accumulating in various organs and releasing their chemical products into tissues. We highlight a patient with Systemic Mastocytosis that caused a pathologic femur fracture in a 63-year-old man with minimal trauma. The typical presentation of bone involvement is a combination of mixed sclerotic and osteolytic lesions, but this patient also had osteopenia. Although bone involvement is common in patients with Systemic Mastocytosis, pathologic fractures outside the vertebral column are rare. The patient was treated with intramedullary fixation of his femur and retained adequate fixation at the time of his death 7 months postoperatively. We review the literature on pathologic fractures outside the vertebral column in patients with Systemic Mastocytosis.
-
Case report: pathologic long bone fracture in a patient with Systemic Mastocytosis.
Clinical orthopaedics and related research, 2007Co-Authors: Joseph J. King, Eileen A. Crawford, O. Hans Iwenofu, Edward J. FoxAbstract:Systemic Mastocytosis is characterized by clonal proliferation of mast cells, which cause disease by accumulating in various organs and releasing their chemical products into tissues. We highlight a patient with Systemic Mastocytosis that caused a pathologic femur fracture in a 63-year-old man with minimal trauma. The typical presentation of bone involvement is a combination of mixed sclerotic and osteolytic lesions, but this patient also had osteopenia. Although bone involvement is common in patients with Systemic Mastocytosis, pathologic fractures outside the vertebral column are rare. The patient was treated with intramedullary fixation of his femur and retained adequate fixation at the time of his death 7 months postoperatively. We review the literature on pathologic fractures outside the vertebral column in patients with Systemic Mastocytosis.
Jason Gotlib - One of the best experts on this subject based on the ideXlab platform.
-
Systemic Mastocytosis version 2 2019 nccn clinical practice guidelines in oncology
Journal of The National Comprehensive Cancer Network, 2018Co-Authors: Jason Gotlib, Mariana Castells, Aaron T Gerds, Prithviraj Bose, Michael W Deininger, Ivana Gojo, Krishna Gundabolu, Gabriela S Hobbs, Catriona Jamieson, Brandon McmahonAbstract:Mastocytosis is a group of heterogeneous disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin and/or in various extracutaneous organs. Systemic Mastocytosis is the most common form of Mastocytosis diagnosed in adults, characterized by mast cell infiltration of one or more extracutaneous organs (with or without skin involvement). The identification of KIT D816V mutation and the emergence of novel targeted therapies have significantly improved the diagnosis and treatment of Systemic Mastocytosis. However, certain aspects of clinical care, particularly the diagnosis, assessment, and management of mediator-related symptoms continue to present challenges. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with Systemic Mastocytosis.
-
efficacy and safety of midostaurin in advanced Systemic Mastocytosis
The New England Journal of Medicine, 2016Co-Authors: Jason Gotlib, Cem Akin, Olivier Hermine, Karl Sotlar, Tracy I George, Hanneke C Kluinnelemans, Farrukh T Awan, Elizabeth O Hexner, Michael J MauroAbstract:BackgroundAdvanced Systemic Mastocytosis comprises rare hematologic neoplasms that are associated with a poor prognosis and lack effective treatment options. The multikinase inhibitor midostaurin inhibits KIT D816V, a primary driver of disease pathogenesis. MethodsWe conducted an open-label study of oral midostaurin at a dose of 100 mg twice daily in 116 patients, of whom 89 with Mastocytosis-related organ damage were eligible for inclusion in the primary efficacy population; 16 had aggressive Systemic Mastocytosis, 57 had Systemic Mastocytosis with an associated hematologic neoplasm, and 16 had mast-cell leukemia. The primary outcome was the best overall response. ResultsThe overall response rate was 60% (95% confidence interval [CI], 49 to 70); 45% of the patients had a major response, which was defined as complete resolution of at least one type of Mastocytosis-related organ damage. Response rates were similar regardless of the subtype of advanced Systemic Mastocytosis, KIT mutation status, or exposure...
-
Mast Cells in Systemic Mastocytosis Have Distinctly Brighter CD45 Expression by Flow Cytometry
American journal of clinical pathology, 2015Co-Authors: Karen M. Chisholm, Tracy I George, Jason Gotlib, Jason D. Merker, Gary M. Gitana, Martina I. Lefterova, James L. Zehnder, Daniel A. Arber, Robert S. OhgamiAbstract:Objectives: We sought to determine the significance of bright CD45 expression on mast cells in cases of Systemic Mastocytosis vs mast cells in bone marrows uninvolved by Systemic Mastocytosis and compare this CD45 expression with CD25 and CD2 expression on mast cells. Methods: Multiparameter flow cytometry was performed on 31 cases of Systemic Mastocytosis and 70 bone marrow cases that were not involved by Systemic Mastocytosis. Bright expression of CD45 was defined as more than 20% of CD117+ mast cells showing brighter CD45 expression than the average expression level of lymphocytes. Results: Mast cells with bright CD45 expression were seen in 26 Systemic Mastocytosis cases and three bone marrows uninvolved by Systemic Mastocytosis (sensitivity, 84%; specificity, 96%). CD25 alone had a greater sensitivity (100%) but lower specificity (93%) compared with bright CD45 for identifying abnormal mast cells, while CD2 alone had lower sensitivity but higher specificity. To reach a specificity of 100%, CD25 together with bright CD45 on mast cells was the optimal combination to detect cases of Systemic Mastocytosis. Conclusions: A combination of bright CD45 and CD25 appears to specifically identify abnormal mast cells in cases of Systemic Mastocytosis. Further studies will be necessary to confirm these results.
Olivier Hermine - One of the best experts on this subject based on the ideXlab platform.
-
efficacy and safety of midostaurin in advanced Systemic Mastocytosis
The New England Journal of Medicine, 2016Co-Authors: Jason Gotlib, Cem Akin, Olivier Hermine, Karl Sotlar, Tracy I George, Hanneke C Kluinnelemans, Farrukh T Awan, Elizabeth O Hexner, Michael J MauroAbstract:BackgroundAdvanced Systemic Mastocytosis comprises rare hematologic neoplasms that are associated with a poor prognosis and lack effective treatment options. The multikinase inhibitor midostaurin inhibits KIT D816V, a primary driver of disease pathogenesis. MethodsWe conducted an open-label study of oral midostaurin at a dose of 100 mg twice daily in 116 patients, of whom 89 with Mastocytosis-related organ damage were eligible for inclusion in the primary efficacy population; 16 had aggressive Systemic Mastocytosis, 57 had Systemic Mastocytosis with an associated hematologic neoplasm, and 16 had mast-cell leukemia. The primary outcome was the best overall response. ResultsThe overall response rate was 60% (95% confidence interval [CI], 49 to 70); 45% of the patients had a major response, which was defined as complete resolution of at least one type of Mastocytosis-related organ damage. Response rates were similar regardless of the subtype of advanced Systemic Mastocytosis, KIT mutation status, or exposure...
-
ivory vertebra and Systemic Mastocytosis
Joint Bone Spine, 2012Co-Authors: Laurent Frenzel, Marie-olivia Chandesris, Felipe Suarez, Olivier HermineAbstract:The ivory vertebra sign seen on a standard radiograph of the spine should prompt investigations for a cause, which is most likely to be a bone metastasis, a lymphoma, or Paget's disease of bone. A diagnosis of idiopathic ivory vertebra can be given if no cause is identified. We report an unusual case of ivory vertebra sign that was due to Systemic Mastocytosis and improved with specific treatment. Although osteoporosis is the most common bone abnormality in Systemic Mastocytosis, an isolated sclerotic or lytic lesion may be found. The ivory vertebra sign should not be considered idiopathic until tests are done for Mastocytosis, particularly given the availability of effective treatments.
Hanneke C. Kluin-nelemans - One of the best experts on this subject based on the ideXlab platform.
-
Advanced Systemic Mastocytosis: from molecular and genetic progress to clinical practice
Haematologica, 2016Co-Authors: Celalettin Ustun, Hanneke C. Kluin-nelemans, Hans-peter Horny, Wolfgang R Sperr, Karin Hartmann, Andreas Reiter, Karl Sotlar, Michel Arock, Tracy George, Gandhi DamajAbstract:Systemic Mastocytosis is a heterogeneous disease characterized by the accumulation of neoplastic mast cells in the bone marrow and other organ organs/tissues. Mutations in KIT, most frequently KIT D816V, are detected in over 80% of all Systemic Mastocytosis patients. While most Systemic Mastocytosis patients suffer from an indolent disease variant, some present with more aggressive variants, collectively called “advanced Systemic Mastocytosis”, which include aggressive Systemic Mastocytosis, Systemic Mastocytosis with an associated hematologic, clonal non mast cell-lineage disease, and mast cell leukemia. Whereas patients with indolent Systemic Mastocytosis have a near normal life expectancy, patients with advanced Systemic Mastocytosis have a reduced life expectancy. Although cladribine and interferon-alpha are of benefit in a group of patients with advanced Systemic Mastocytosis, no curative therapy is available for these patients except possible allogeneic hematopoietic stem cell transplantation. Recent studies have also revealed additional somatic defects (apart from mutations in KIT) in a majority of patients with advanced Systemic Mastocytosis. These include TET2, SRSF2, ASXL1, RUNX1, JAK2, and/or RAS mutations, which may adversely impact prognosis and survival in particular Systemic Mastocytosis with an associated hematological neoplasm. In addition, several additional signaling molecules involved in the abnormal proliferation of mast cells in Systemic Mastocytosis have been identified. These advances have led to a better understanding of the biology of advanced Systemic Mastocytosis and to the development of new targeted treatment concepts. Herein, we review the biology and pathogenesis of advanced Systemic Mastocytosis, with a special focus on novel molecular findings as well as current and evolving therapeutic options.
-
Biochemical markers predictive for bone marrow involvement in Systemic Mastocytosis.
Haematologica, 2008Co-Authors: Marjolein L. Donker, Frederiek F. Van Doormaal, Eveline Van Der Veer, Jan G.r. De Monchy, Jasper J. Van Doormaal, Philip M Kluin, Ido P. Kema, Hanneke C. Kluin-nelemansAbstract:Systemic Mastocytosis is characterized by bone marrow involvement, which requires a bone marrow biopsy for diagnostic work-up. We questioned whether bone marrow involvement could be predicted using biochemical markers. We selected patients with various symptoms suggestive of indolent Systemic Mastocytosis, of whom 63 ultimately had bone marrow involvement. Patients suspected of aggressive Mastocytosis, or Mastocytosis associated with other hematologic diseases were excluded. Evaluation of 115 patients and 15 patient controls demonstrated a test accuracy for serum tryptase, urinary N− methylhistamine and N− methylimidazole acetic acid of 96%, 88% and 95% respectively. These markers provide an excellent pre-test probability of indolent Systemic Mastocytosis.
