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Cem Akin - One of the best experts on this subject based on the ideXlab platform.
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A Challenge for Allergologist: Application of Allergy Diagnostic Methods in Mast Cell Disorders
International Journal of Molecular Sciences, 2021Co-Authors: Jan Romantowski, Aleksandra Gorska, Marek Niedoszytko, Michel Arock, Magdalena Lange, Knut Brockow, Theo Gulen, Marta Gruchała-niedoszytko, Bogusław Nedoszytko, Cem AkinAbstract:Primary and secondary mast cell activation syndromes (MCAS) can occur in patients with Mastocytosis. During the past few years our knowledge about the pathogenesis and disease-triggering mechanisms in MCAS and Mastocytosis have increased substantially. Whereas Mastocytosis is characterized by an accumulation of neoplastic (clonal) mast cells (MC) in various organ systems, MCAS is defined by a massive and systemic activation of these cells. Mast cells are crucial effector cells in allergic diseases, thus their elevated number and activation can cause severe anaphylactic reactions and MCAS in patients with Mastocytosis. However, these cells may also degranulate spontaneously or degranulate in response to non-allergic triggers leading to clinical symptoms. In Mastocytosis patients, such symptoms may lead to the diagnosis of a primary MCAS. The diagnosis of a concomitant allergy in Mastocytosis patients is challenging. In these patients, a mixed form (primary and secondary) of MCAS may be diagnosed. These patients may also suffer from life-threatening anaphylactic reactions when exposed to allergens. In these cases, the possibility of severe side effects of in vivo provocations can sometimes also limit diagnostic evaluations. In the current article, we discuss the diagnosis and management of patients suffering from Mastocytosis and concomitant MCAS, with special emphasis on novel diagnostic tests and management, including allergen microarrays, recombinant allergen analysis, basophil activation tests, optimal prophylaxis, and specific therapies
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History and Current Status of Mastocytosis Research in the European Competence Network on Mastocytosis
Mastocytosis, 2019Co-Authors: Peter Valent, Wolfgang R Sperr, Emir Hadzijusufovic, Cem Akin, Karin Hartmann, Michel Arock, Dean D. Metcalfe, Hans-peter HornyAbstract:Mastocytosis is a unique and rare hematologic neoplasm characterized by abnormal expansion and accumulation of tissue mast cells in various organ systems. The clinical course and prognosis vary among patients, depending on the category of disease, comorbidities, and patient-related features. The cutaneous lesions of Mastocytosis were first described by Nettleship and Tay in 1869. In the twentieth century, systemic forms of Mastocytosis were identified and grouped into indolent and aggressive (advanced) variants. Between 1990 and 2000, diagnostic criteria and a classification of Mastocytosis were established by an EU/US consensus group, and this classification was adopted by the World Health Organization (WHO) in 2001. In 2002, the European Competence Network on Mastocytosis (ECNM) was inaugurated and started. Expert representatives of this network and the consensus group served as major participants and advocates of Mastocytosis research in Europe and in the USA over the past 20 years. Their achievements and the resulting clinical concepts and guidelines are summarized in the present article.
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Management of Mastocytosis in Pregnancy: A Review.
The journal of allergy and clinical immunology. In practice, 2017Co-Authors: Dawn Lei, Cem Akin, Anna KovalszkiAbstract:In this article, the authors present a case of pregnancy complicated by the need for management of indolent systemic Mastocytosis. The diagnosis of Mastocytosis is reviewed, as well as subtypes of Mastocytosis and management options particularly in pregnancy. A table of pregnancy/lactaction categories for common medications used in Mastocytosis is presented.
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advances in the classification and treatment of Mastocytosis current status and outlook toward the future
Cancer Research, 2017Co-Authors: Peter Valent, Luis Escribano, Wolfgang R Sperr, Cem Akin, Karin Hartmann, Gunnar Nilsson, Andreas Reiter, Olivier Hermine, Karl Sotlar, Tracy I GeorgeAbstract:Mastocytosis is a term used to denote a heterogeneous group of conditions defined by the expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous Mastocytosis, systemic Mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic Mastocytosis is further divided into indolent systemic Mastocytosis and advanced systemic Mastocytosis variants, including aggressive systemic Mastocytosis and mast cell leukemia. The clinical impact and prognostic value of this classification has been confirmed in numerous studies, and its basic concept remains valid. However, refinements have recently been proposed by the consensus group, the WHO, and the European Competence Network on Mastocytosis. In addition, new treatment options are available for patients with advanced systemic Mastocytosis, including allogeneic hematopoietic stem cell transplantation and multikinase inhibitors directed against KIT D816V and other key signaling molecules. Our current article provides an overview of recent advances in the field of Mastocytosis, with emphasis on classification, prognostication, and emerging new treatment options in advanced systemic Mastocytosis. (C)2017 AACR.
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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...
Emir Hadzijusufovic - One of the best experts on this subject based on the ideXlab platform.
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Clinical Impact of Skin Lesions in Mastocytosis: A Multicenter Study of the European Competence Network on Mastocytosis (ECNM).
The Journal of investigative dermatology, 2021Co-Authors: Elisabeth Aberer, Wolfgang R Sperr, Bjorn Van Anrooij, Marek Niedoszytko, Emir Hadzijusufovic, Hanneke C Kluin-nelemans, Agnes Bretterklieber, Alexander Avian, Hanneke Oude Elberink, Magdalena LangeAbstract:Mastocytosis is a rare neoplasm characterized by expansion and accumulation of mast cells in various organ systems. Systemic Mastocytosis (SM) may or may not presents with cutaneous lesions. To examine the frequency and clinical impact of cutaneous involvement, 1510 Mastocytosis patients collected in the registry of the European Competence Network on Mastocytosis were analyzed. Cutaneous involvement was found in 1195/1510 (79.1%) patients. Of these, 286 had cutaneous Mastocytosis (CM) and 721 had SM with skin involvement (SM+). Adult patients with skin involvement who did not have a bone marrow examination (n=188) were defined as Mastocytosis in the skin (MIS). In 315 patients with SM, no skin involvement was found (SM-). The percentage of cases with cutaneous involvement was higher in indolent SM (100%) and smoldering SM (87.9%) compared to aggressive SM (46.8%) or mast cell leukemia (38.5%). After a median follow-up of 5.6 years no patient with CM had died, but 2.6% of the patients with MIS, 5.7% with SM+ and 28.95% with SM- had died. Overall survival was longer in patients with skin involvement (CM/MIS/SM+) compared to SM- patients (p
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History and Current Status of Mastocytosis Research in the European Competence Network on Mastocytosis
Mastocytosis, 2019Co-Authors: Peter Valent, Wolfgang R Sperr, Emir Hadzijusufovic, Cem Akin, Karin Hartmann, Michel Arock, Dean D. Metcalfe, Hans-peter HornyAbstract:Mastocytosis is a unique and rare hematologic neoplasm characterized by abnormal expansion and accumulation of tissue mast cells in various organ systems. The clinical course and prognosis vary among patients, depending on the category of disease, comorbidities, and patient-related features. The cutaneous lesions of Mastocytosis were first described by Nettleship and Tay in 1869. In the twentieth century, systemic forms of Mastocytosis were identified and grouped into indolent and aggressive (advanced) variants. Between 1990 and 2000, diagnostic criteria and a classification of Mastocytosis were established by an EU/US consensus group, and this classification was adopted by the World Health Organization (WHO) in 2001. In 2002, the European Competence Network on Mastocytosis (ECNM) was inaugurated and started. Expert representatives of this network and the consensus group served as major participants and advocates of Mastocytosis research in Europe and in the USA over the past 20 years. Their achievements and the resulting clinical concepts and guidelines are summarized in the present article.
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international prognostic scoring system for Mastocytosis ipsm a retrospective cohort study
The Lancet Haematology, 2019Co-Authors: Wolfgang R Sperr, Michael Kundi, Ivan Alvareztwose, Bjorn Van Anrooij, Joanna Oude N G Elberink, Aleksandra Gorska, Marek Niedoszytko, Karoline V Gleixner, Emir HadzijusufovicAbstract:Summary Background The WHO classification separates Mastocytosis into distinct variants, but prognostication remains a clinical challenge. The aim of this study was to improve prognostication for patients with Mastocytosis. Methods We analysed data of the registry of the European Competence Network on Mastocytosis including 1639 patients (age 17–90 years) diagnosed with Mastocytosis according to WHO criteria between Jan 12, 1978, and March 16, 2017. Univariate and multivariate analyses with Cox regression were applied to identify prognostic variables predicting survival outcomes and to establish a prognostic score. We validated this International Prognostic Scoring System in Mastocytosis (IPSM) with data of 462 patients (age 17–79 years) from the Spanish network Red Espanola de Mastocitosis diagnosed between Jan 22, 1998, and Nov 2, 2017. Findings The prognostic value of the WHO classification was confirmed in our study (p Interpretation The IPSM scores for patients with non-advanced and advanced Mastocytosis can be used to predict survival outcomes and guide treatment decisions. However, the predictive value of the IPSM needs to be confirmed in forthcoming trials. Funding Austrian Science Fund, Deutsche Forschungsgemeinschaft, Koeln Fortune Program, Charles and Ann Johnson Foundation, Instituto de Salud Carlos III, Fondos FEDER, Research-Foundation Flanders/Fonds Wetenschappelijk Onderzoek, Clinical Research-Fund of the University Hospitals Leuven, and Research-Foundation Flanders/Fonds Wetenschappelijk Onderzoek.
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the data registry of the european competence network on Mastocytosis ecnm set up projects and perspectives
The Journal of Allergy and Clinical Immunology: In Practice, 2019Co-Authors: Peter Valent, Roberta Zanotti, Patrizia Bonadonna, Bjorn Van Anrooij, Joanna Oude N G Elberink, Aleksandra Gorska, Karoline V Gleixner, Magdalena Lange, Massimiliano Bonifacio, Emir HadzijusufovicAbstract:Mastocytosis is a unique hematologic neoplasm with complex biology and pathology and a variable clinical course. The disease can essentially be divided into cutaneous Mastocytosis (CM) and systemic Mastocytosis (SM). In adults, SM is diagnosed in most cases and manifests as either indolent or advanced disease. Patients with advanced SM have an unfavorable prognosis with reduced survival. However, so far, little is known about the prevalence of various categories of SM and about prognostic factors. In an attempt to learn more about the behavior and evolution of various forms of CM and SM, the European Competence Network on Mastocytosis (ECNM) initiated a Mastocytosis registry in 2012. In this article, the set up and start phase of this registry are described. Until 2018, more than 3000 patients from 12 countries and 25 centers have been enrolled. In a majority of all patients, robust follow-up data and relevant clinical end points are available. Using this data set, a series of registry projects have been launched, with the aim to validate previously identified diagnostic and prognostic variables and to identify new disease-related and patient-related parameters in various forms of Mastocytosis. Moreover, the core data set of the registry will be useful to establish multiparametric scoring systems through which prognostication and individualized management of patients with Mastocytosis should improve in the foreseeable future.
Luis Escribano - One of the best experts on this subject based on the ideXlab platform.
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advances in the classification and treatment of Mastocytosis current status and outlook toward the future
Cancer Research, 2017Co-Authors: Peter Valent, Luis Escribano, Wolfgang R Sperr, Cem Akin, Karin Hartmann, Gunnar Nilsson, Andreas Reiter, Olivier Hermine, Karl Sotlar, Tracy I GeorgeAbstract:Mastocytosis is a term used to denote a heterogeneous group of conditions defined by the expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous Mastocytosis, systemic Mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic Mastocytosis is further divided into indolent systemic Mastocytosis and advanced systemic Mastocytosis variants, including aggressive systemic Mastocytosis and mast cell leukemia. The clinical impact and prognostic value of this classification has been confirmed in numerous studies, and its basic concept remains valid. However, refinements have recently been proposed by the consensus group, the WHO, and the European Competence Network on Mastocytosis. In addition, new treatment options are available for patients with advanced systemic Mastocytosis, including allogeneic hematopoietic stem cell transplantation and multikinase inhibitors directed against KIT D816V and other key signaling molecules. Our current article provides an overview of recent advances in the field of Mastocytosis, with emphasis on classification, prognostication, and emerging new treatment options in advanced systemic Mastocytosis. (C)2017 AACR.
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increased serum baseline tryptase levels and extensive skin involvement are predictors for the severity of mast cell activation episodes in children with Mastocytosis
Allergy, 2012Co-Authors: Ivan Alvareztwose, Lawrence B. Schwartz, Sergio Vanogalvan, Jose Mario Morgado, Almudena Matito, Antonio Torrelo, A. Orfao, Laura Sanchezmunoz, Pedro Jaen, Luis EscribanoAbstract:Currently, the World Health Organization (WHO) recognizes three major variants of Mastocytosis in the skin (MIS): maculopapular cutaneous Mastocytosis (MPCM), diffuse cutaneous Mastocytosis (DCM), and solitary mastocytoma (1, 2). However, other variants of MIS have also been reported, including plaque (PM), nodular (NM) and telangiectatic cutaneous Mastocytosis (3); in addition, criteria for the diagnosis of MIS have been proposed (4). It has been reported that serum baseline total tryptase (sbT) levels >20 µg/l in pediatric cutaneous Mastocytosis (CM) reflect either extensive skin involvement or the possibility of systemic disease (5). Total tryptase levels include both mature and pro forms of tryptase; protryptase is spontaneously and continuously secreted by unstimulated mast cells (MC), while mature tryptase is stored in secretory granules until MC are activated to degranulate. Nevertheless, the true significance of increased sbT levels at onset of pediatric Mastocytosis remains unclear. Although it has been proven that serum mature tryptase (smT) levels transiently increase in most subjects with severe systemic anaphylaxis in association with hypotension (6) and that detectable smT levels with a total tryptase/mature tryptase ratio ≤10 reflect systemic anaphylaxis (7), the exact percentage of patients at risk for severe MC mediator-related symptoms remains unknown. Here, we investigated the potential association between clinical and laboratory data and the development of MC-related symptoms in a series of 111 children with Mastocytosis, within the first 18 months after disease onset. Overall, our results support a direct relationship between sbT levels and the extent of skin involvement in pediatric Mastocytosis and a potential role for sbT levels at diagnosis in predicting the clinical severity in our population.
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Childhood Mastocytosis.
Current opinion in pediatrics, 2012Co-Authors: Antonio Torrelo, Ivan Alvarez-twose, Luis EscribanoAbstract:Important advances have been achieved in recent years in adult Mastocytosis. However, our knowledge about childhood Mastocytosis is limited because invasive tests are not routinely performed in children. We ignore the frequency of systemic involvement in childhood Mastocytosis, its outcome, and which are the main clinical and laboratory parameters associated with persistence into adult Mastocytosis and its severity. Childhood Mastocytosis is a clonal mast cell disease, with different activating mutations in the KIT gene discovered in most patients. Serum tryptase is the best marker for mast cell burden in children, and, at baseline, correlates well with the severity of symptoms in childhood Mastocytosis. Systemic Mastocytosis definitely may occur in children, but bone marrow studies to demonstrate a systemic involvement are not routinely performed nor recommended; it can be estimated that around 30% of children may have bone marrow involvement as demonstrated by showing aggregates of mast cells or by flow cytometry of mast cells expressing the aberrant CD25 marker. A new and improved classification of childhood Mastocytosis is needed, and should be based on the correlation of clinical manifestations, morphology of mast cells in the skin, and the predicted outcome of the disease. The current classifications of childhood Mastocytosis do not address any of these important issues.
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dermoscopic features of skin lesions in patients with Mastocytosis
Archives of Dermatology, 2011Co-Authors: Sergio Vanogalvan, Ivan Alvareztwose, Elena De Las Heras, Jose Mario Morgado, Almudena Matito, Laura Anchezmu S Noz, Maria N Plana, Alberto Orfao, Luis EscribanoAbstract:Objectives To evaluate dermoscopic features in a group of 127 patients with Mastocytosis in the skin and to investigate the relationship between different dermoscopic patterns and other clinical and biological characteristics of the disease. Design Clinical and laboratory data were compared among patients with Mastocytosis grouped according to the different dermoscopic patterns. Setting Patients were selected from the Instituto de Estudios de Mastocitosis de Castilla La Mancha and the Department of Dermatology of Hospital Universitario Ram on y Cajal from April 1 through September 30, 2009. Patients Overall, 127 consecutive patients (70 females [55.1%] and 57 males [44.9%]; median age, 17 years; range, 0-81 years) with Mastocytosis in the skin were included in the study. Main Outcome Measures Evaluation of dermoscopic patterns and investigation of potential predictive factors for more symptomatic forms of the disease according to the need for daily antimediator therapy. Results Four distinct dermoscopic patterns were observed: yellow-orange blot, pigment network, reticular vascular pattern, and (most frequently) light-brown blot. A reticular vascular pattern was identified in all telangiectasia macular eruptiva and some maculopapular Mastocytosis. In turn, all patients with mastocytoma displayed the yellow-orange blot pattern. The reticular vascular dermoscopic pattern was associated with the need for daily antimediator therapy; this pattern, together with serum tryptase levels and plaque-type Mastocytosis, represented the best combination of independent factors to predict the need for maintained antimediator therapy. Conclusions Dermoscopy is a feasible method for the subclassification of Mastocytosis. Of note, a reticular vascular pattern is more frequently associated with the need for antimediator therapy.
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evolution of urticaria pigmentosa into indolent systemic Mastocytosis abnormal immunophenotype of mast cells without evidence of c kit mutation asp 816 val
Leukemia & Lymphoma, 2003Co-Authors: Frank Noack, Luis Escribano, K Sotla, Rosa Nunez, Konard Schuetze, Pete Vale, Hans-peter HornyAbstract:Mastocytosis comprises a heterogeneous group of hematological disorders which are morphologically defined by proliferation and accumulation of tissue mast cells in one or more organs. Clinical manifestations of Mastocytosis range from disseminated maculopapular skin lesions (=urticaria pigmentosa [UP]) that may spontaneously regress to highly aggressive neoplasms like mast cell leukemia or mast cell sarcoma. Recently, it could be shown that systemic Mastocytosis (SM) is a clonal disorder often exhibiting mutations of c-kit, a protooncogene encoding the tyrosine kinase receptor for stem cell factor (SCF). Mutations of c-kit are considered to play a key role in the pathogenesis of Mastocytosis. Therefore, we investigated the unique case of a 36 year-old male patient with indolent systemic Mastocytosis (ISM) evolving from UP (cutaneous Mastocytosis) by means of histology, immunophenotyping and molecular biology. At the time of initial diagnosis the bone marrow showed only a mild diffuse increase in mast cell...
Wolfgang R Sperr - One of the best experts on this subject based on the ideXlab platform.
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Clinical Impact of Skin Lesions in Mastocytosis: A Multicenter Study of the European Competence Network on Mastocytosis (ECNM).
The Journal of investigative dermatology, 2021Co-Authors: Elisabeth Aberer, Wolfgang R Sperr, Bjorn Van Anrooij, Marek Niedoszytko, Emir Hadzijusufovic, Hanneke C Kluin-nelemans, Agnes Bretterklieber, Alexander Avian, Hanneke Oude Elberink, Magdalena LangeAbstract:Mastocytosis is a rare neoplasm characterized by expansion and accumulation of mast cells in various organ systems. Systemic Mastocytosis (SM) may or may not presents with cutaneous lesions. To examine the frequency and clinical impact of cutaneous involvement, 1510 Mastocytosis patients collected in the registry of the European Competence Network on Mastocytosis were analyzed. Cutaneous involvement was found in 1195/1510 (79.1%) patients. Of these, 286 had cutaneous Mastocytosis (CM) and 721 had SM with skin involvement (SM+). Adult patients with skin involvement who did not have a bone marrow examination (n=188) were defined as Mastocytosis in the skin (MIS). In 315 patients with SM, no skin involvement was found (SM-). The percentage of cases with cutaneous involvement was higher in indolent SM (100%) and smoldering SM (87.9%) compared to aggressive SM (46.8%) or mast cell leukemia (38.5%). After a median follow-up of 5.6 years no patient with CM had died, but 2.6% of the patients with MIS, 5.7% with SM+ and 28.95% with SM- had died. Overall survival was longer in patients with skin involvement (CM/MIS/SM+) compared to SM- patients (p
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History and Current Status of Mastocytosis Research in the European Competence Network on Mastocytosis
Mastocytosis, 2019Co-Authors: Peter Valent, Wolfgang R Sperr, Emir Hadzijusufovic, Cem Akin, Karin Hartmann, Michel Arock, Dean D. Metcalfe, Hans-peter HornyAbstract:Mastocytosis is a unique and rare hematologic neoplasm characterized by abnormal expansion and accumulation of tissue mast cells in various organ systems. The clinical course and prognosis vary among patients, depending on the category of disease, comorbidities, and patient-related features. The cutaneous lesions of Mastocytosis were first described by Nettleship and Tay in 1869. In the twentieth century, systemic forms of Mastocytosis were identified and grouped into indolent and aggressive (advanced) variants. Between 1990 and 2000, diagnostic criteria and a classification of Mastocytosis were established by an EU/US consensus group, and this classification was adopted by the World Health Organization (WHO) in 2001. In 2002, the European Competence Network on Mastocytosis (ECNM) was inaugurated and started. Expert representatives of this network and the consensus group served as major participants and advocates of Mastocytosis research in Europe and in the USA over the past 20 years. Their achievements and the resulting clinical concepts and guidelines are summarized in the present article.
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international prognostic scoring system for Mastocytosis ipsm a retrospective cohort study
The Lancet Haematology, 2019Co-Authors: Wolfgang R Sperr, Michael Kundi, Ivan Alvareztwose, Bjorn Van Anrooij, Joanna Oude N G Elberink, Aleksandra Gorska, Marek Niedoszytko, Karoline V Gleixner, Emir HadzijusufovicAbstract:Summary Background The WHO classification separates Mastocytosis into distinct variants, but prognostication remains a clinical challenge. The aim of this study was to improve prognostication for patients with Mastocytosis. Methods We analysed data of the registry of the European Competence Network on Mastocytosis including 1639 patients (age 17–90 years) diagnosed with Mastocytosis according to WHO criteria between Jan 12, 1978, and March 16, 2017. Univariate and multivariate analyses with Cox regression were applied to identify prognostic variables predicting survival outcomes and to establish a prognostic score. We validated this International Prognostic Scoring System in Mastocytosis (IPSM) with data of 462 patients (age 17–79 years) from the Spanish network Red Espanola de Mastocitosis diagnosed between Jan 22, 1998, and Nov 2, 2017. Findings The prognostic value of the WHO classification was confirmed in our study (p Interpretation The IPSM scores for patients with non-advanced and advanced Mastocytosis can be used to predict survival outcomes and guide treatment decisions. However, the predictive value of the IPSM needs to be confirmed in forthcoming trials. Funding Austrian Science Fund, Deutsche Forschungsgemeinschaft, Koeln Fortune Program, Charles and Ann Johnson Foundation, Instituto de Salud Carlos III, Fondos FEDER, Research-Foundation Flanders/Fonds Wetenschappelijk Onderzoek, Clinical Research-Fund of the University Hospitals Leuven, and Research-Foundation Flanders/Fonds Wetenschappelijk Onderzoek.
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advances in the classification and treatment of Mastocytosis current status and outlook toward the future
Cancer Research, 2017Co-Authors: Peter Valent, Luis Escribano, Wolfgang R Sperr, Cem Akin, Karin Hartmann, Gunnar Nilsson, Andreas Reiter, Olivier Hermine, Karl Sotlar, Tracy I GeorgeAbstract:Mastocytosis is a term used to denote a heterogeneous group of conditions defined by the expansion and accumulation of clonal (neoplastic) tissue mast cells in various organs. The classification of the World Health Organization (WHO) divides the disease into cutaneous Mastocytosis, systemic Mastocytosis, and localized mast cell tumors. On the basis of histomorphologic criteria, clinical parameters, and organ involvement, systemic Mastocytosis is further divided into indolent systemic Mastocytosis and advanced systemic Mastocytosis variants, including aggressive systemic Mastocytosis and mast cell leukemia. The clinical impact and prognostic value of this classification has been confirmed in numerous studies, and its basic concept remains valid. However, refinements have recently been proposed by the consensus group, the WHO, and the European Competence Network on Mastocytosis. In addition, new treatment options are available for patients with advanced systemic Mastocytosis, including allogeneic hematopoietic stem cell transplantation and multikinase inhibitors directed against KIT D816V and other key signaling molecules. Our current article provides an overview of recent advances in the field of Mastocytosis, with emphasis on classification, prognostication, and emerging new treatment options in advanced systemic Mastocytosis. (C)2017 AACR.
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Advanced systemic Mastocytosis: from molecular and genetic progress to clinical practice
Haematologica, 2016Co-Authors: Celalettin Ustun, Hans-peter Horny, Wolfgang R Sperr, Karin Hartmann, Andreas Reiter, Karl Sotlar, Michel Arock, Hanneke C Kluin-nelemans, 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.
Marek Niedoszytko - One of the best experts on this subject based on the ideXlab platform.
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Clinical Impact of Skin Lesions in Mastocytosis: A Multicenter Study of the European Competence Network on Mastocytosis (ECNM).
The Journal of investigative dermatology, 2021Co-Authors: Elisabeth Aberer, Wolfgang R Sperr, Bjorn Van Anrooij, Marek Niedoszytko, Emir Hadzijusufovic, Hanneke C Kluin-nelemans, Agnes Bretterklieber, Alexander Avian, Hanneke Oude Elberink, Magdalena LangeAbstract:Mastocytosis is a rare neoplasm characterized by expansion and accumulation of mast cells in various organ systems. Systemic Mastocytosis (SM) may or may not presents with cutaneous lesions. To examine the frequency and clinical impact of cutaneous involvement, 1510 Mastocytosis patients collected in the registry of the European Competence Network on Mastocytosis were analyzed. Cutaneous involvement was found in 1195/1510 (79.1%) patients. Of these, 286 had cutaneous Mastocytosis (CM) and 721 had SM with skin involvement (SM+). Adult patients with skin involvement who did not have a bone marrow examination (n=188) were defined as Mastocytosis in the skin (MIS). In 315 patients with SM, no skin involvement was found (SM-). The percentage of cases with cutaneous involvement was higher in indolent SM (100%) and smoldering SM (87.9%) compared to aggressive SM (46.8%) or mast cell leukemia (38.5%). After a median follow-up of 5.6 years no patient with CM had died, but 2.6% of the patients with MIS, 5.7% with SM+ and 28.95% with SM- had died. Overall survival was longer in patients with skin involvement (CM/MIS/SM+) compared to SM- patients (p
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A Challenge for Allergologist: Application of Allergy Diagnostic Methods in Mast Cell Disorders
International Journal of Molecular Sciences, 2021Co-Authors: Jan Romantowski, Aleksandra Gorska, Marek Niedoszytko, Michel Arock, Magdalena Lange, Knut Brockow, Theo Gulen, Marta Gruchała-niedoszytko, Bogusław Nedoszytko, Cem AkinAbstract:Primary and secondary mast cell activation syndromes (MCAS) can occur in patients with Mastocytosis. During the past few years our knowledge about the pathogenesis and disease-triggering mechanisms in MCAS and Mastocytosis have increased substantially. Whereas Mastocytosis is characterized by an accumulation of neoplastic (clonal) mast cells (MC) in various organ systems, MCAS is defined by a massive and systemic activation of these cells. Mast cells are crucial effector cells in allergic diseases, thus their elevated number and activation can cause severe anaphylactic reactions and MCAS in patients with Mastocytosis. However, these cells may also degranulate spontaneously or degranulate in response to non-allergic triggers leading to clinical symptoms. In Mastocytosis patients, such symptoms may lead to the diagnosis of a primary MCAS. The diagnosis of a concomitant allergy in Mastocytosis patients is challenging. In these patients, a mixed form (primary and secondary) of MCAS may be diagnosed. These patients may also suffer from life-threatening anaphylactic reactions when exposed to allergens. In these cases, the possibility of severe side effects of in vivo provocations can sometimes also limit diagnostic evaluations. In the current article, we discuss the diagnosis and management of patients suffering from Mastocytosis and concomitant MCAS, with special emphasis on novel diagnostic tests and management, including allergen microarrays, recombinant allergen analysis, basophil activation tests, optimal prophylaxis, and specific therapies
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international prognostic scoring system for Mastocytosis ipsm a retrospective cohort study
The Lancet Haematology, 2019Co-Authors: Wolfgang R Sperr, Michael Kundi, Ivan Alvareztwose, Bjorn Van Anrooij, Joanna Oude N G Elberink, Aleksandra Gorska, Marek Niedoszytko, Karoline V Gleixner, Emir HadzijusufovicAbstract:Summary Background The WHO classification separates Mastocytosis into distinct variants, but prognostication remains a clinical challenge. The aim of this study was to improve prognostication for patients with Mastocytosis. Methods We analysed data of the registry of the European Competence Network on Mastocytosis including 1639 patients (age 17–90 years) diagnosed with Mastocytosis according to WHO criteria between Jan 12, 1978, and March 16, 2017. Univariate and multivariate analyses with Cox regression were applied to identify prognostic variables predicting survival outcomes and to establish a prognostic score. We validated this International Prognostic Scoring System in Mastocytosis (IPSM) with data of 462 patients (age 17–79 years) from the Spanish network Red Espanola de Mastocitosis diagnosed between Jan 22, 1998, and Nov 2, 2017. Findings The prognostic value of the WHO classification was confirmed in our study (p Interpretation The IPSM scores for patients with non-advanced and advanced Mastocytosis can be used to predict survival outcomes and guide treatment decisions. However, the predictive value of the IPSM needs to be confirmed in forthcoming trials. Funding Austrian Science Fund, Deutsche Forschungsgemeinschaft, Koeln Fortune Program, Charles and Ann Johnson Foundation, Instituto de Salud Carlos III, Fondos FEDER, Research-Foundation Flanders/Fonds Wetenschappelijk Onderzoek, Clinical Research-Fund of the University Hospitals Leuven, and Research-Foundation Flanders/Fonds Wetenschappelijk Onderzoek.
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clinical aspects of paediatric Mastocytosis a review of 101 cases
Journal of The European Academy of Dermatology and Venereology, 2013Co-Authors: Magdalena Lange, Marek Niedoszytko, Joanna Renke, Jolanta Glen, Boguslaw NedoszytkoAbstract:Background Cutaneous Mastocytosis (CM) is a typical presentation of Mastocytosis in children. However, systemic Mastocytosis may also occur in children. Objective We tried to characterize the clinical features of childhood-onset Mastocytosis and estimate the value of the SCORMA (SCORing Mastocytosis) Index and serum tryptase levels as disease severity parameters. Methods In a survey of 101 children Mastocytosis was diagnosed and classified according to World Health Organization criteria. In all the cases serum tryptase levels and the SCORMA Index were done to assess the extent and intensity of the disease. Results Cutaneous Mastocytosis was diagnosed in 100 children; 84% of them presented maculopapular CM, 10% mastocytoma and 6% diffuse cutaneous Mastocytosis. Moreover, systemic Mastocytosis with bone marrow infiltration and associated with maculopapular CM was found in one case. There was a positive correlation of serum tryptase level to the SCORMA Index. Both the mean tryptase level and the mean SCORMA Index were elevated in diffuse cutaneous Mastocytosis children when compared with other forms CM. A significantly higher mean tryptase level was found in children with flushing, hypotension, diarrhoea, extensive bullous lesions and osteoporosis or osteopenia. Conclusion Mastocytosis in children usually has a benign course. Nevertheless, severe mediator-related symptoms and systemic involvement may appear. Therefore, a multidisciplinary approach involving careful monitoring of the serum tryptase level, SCORMA Index and the organ function is recommended. Both tryptase levels and the SCORMA Index are of a great value as disease severity parameters and they should be assessed simultaneously in all Mastocytosis patients.
