| 1. |
- Engert, Andreas, et al.
(författare)
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The European Hematology Association Roadmap for European Hematology Research : a consensus document
- 2016
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Ingår i: Haematologica. - Pavia, Italy : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 101:2, s. 115-208
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Tidskriftsartikel (refereegranskat)abstract
- The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at (sic)23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
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| 2. |
- Kluin-Nelemans, Hanneke C., et al.
(författare)
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Prognostic impact of eosinophils in mastocytosis : analysis of 2350 patients collected in the ECNM Registry
- 2020
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Ingår i: Leukemia. - : Nature Publishing Group. - 0887-6924 .- 1476-5551. ; 34:4, s. 1090-1101
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Tidskriftsartikel (refereegranskat)abstract
- Systemic mastocytosis (SM) is frequently associated with eosinophilia. To examine its prevalence and clinical impact in all WHO classification-based subcategories, we analyzed eosinophil counts in 2350 mastocytosis patients using the dataset of the European Competence Network on Mastocytosis. Ninety percent of patients had normal eosinophil counts, 6.8% mild eosinophilia (0.5-1.5x10(9)/l), and 3.1% hypereosinophilia (HE; >1.5x10(9)/l). Eosinophilia/HE were mainly present in patients with advanced SM (17%/19%), and only rarely recorded in patients with indolent and smoldering SM (5%/1%), and some patients with cutaneous mastocytosis. The eosinophil count correlated with organomegaly, dysmyelopoiesis, and the WHO classification, but not with mediator-related symptoms or allergy. Eosinophilia at diagnosis had a strong prognostic impact (p<0.0001) on overall survival (OS) and progression-free survival (PFS), with a 10-year OS of 19% for patients with HE, 70% for those with mild eosinophilia, and 88% for patients with normal eosinophil counts. In 89% of patients with follow-up data (n=1430, censored at start of cytoreductive therapy), eosinophils remained stable. In those with changing eosinophil counts (increase/decrease or mixed pattern), OS and PFS were inferior compared with patients with stable eosinophil counts. In conclusion, eosinophilia and HE are more prevalent in advanced SM and are predictors of a worse outcome.
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| 3. |
- Valent, Peter, et al.
(författare)
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The Data Registry of the European Competence Network on Mastocytosis (ECNM) : Set Up, Projects, and Perspectives
- 2019
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Ingår i: Journal of Allergy and Clinical Immunology. - : ELSEVIER SCIENCE BV. - 2213-2198 .- 2213-2201. ; 7:1, s. 81-87
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Forskningsöversikt (refereegranskat)abstract
- 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. (C) 2019 American Academy of Allergy, Asthma & Immunology
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| 4. |
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| 5. |
- Bastard, Paul, et al.
(författare)
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Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1.
- 2021
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Ingår i: The Journal of experimental medicine. - 1540-9538. ; 218:7
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Tidskriftsartikel (refereegranskat)abstract
- Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
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| 6. |
- Coulon, Severine, et al.
(författare)
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Polymeric IgA1 controls erythroblast proliferation and accelerates erythropoiesis recovery in anemia
- 2011
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 17:11, s. 163-1456
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Tidskriftsartikel (refereegranskat)abstract
- Anemia because of insufficient production of and/or response to erythropoietin (Epo) is a major complication of chronic kidney disease and cancer. The mechanisms modulating the sensitivity of erythroblasts to Epo remain poorly understood. We show that, when cultured with Epo at suboptimal concentrations, the growth and clonogenic potential of erythroblasts was rescued by transferrin receptor 1 (TfR1)-bound polymeric IgA1 (pIgA1). Under homeostatic conditions, erythroblast numbers were increased in mice expressing human IgA1 compared to control mice. Hypoxic stress of these mice led to increased amounts of pIgA1 and erythroblast expansion. Expression of human IgA1 or treatment of wild-type mice with the TfR1 ligands pIgA1 or iron-loaded transferrin (Fe-Tf) accelerated recovery from acute anemia. TfR1 engagement by either pIgA1 or Fe-Tf increased cell sensitivity to Epo by inducing activation of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways. These cellular responses were mediated through the TfR1-internalization motif, YXX Phi. Our results show that pIgA1 and TfR1 are positive regulators of erythropoiesis in both physiological and pathological situations. Targeting this pathway may provide alternate approaches to the treatment of ineffective erythropoiesis and anemia.
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| 7. |
- Dreyling, Martin, et al.
(författare)
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Treatment for patients with relapsed/refractory mantle cell lymphoma : European-based recommendations
- 2018
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 59:8, s. 1814-1828
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Tidskriftsartikel (refereegranskat)abstract
- Patients with mantle cell lymphoma (MCL) usually respond to initial combination chemotherapy, but the disease inevitably relapses and often follows an aggressive course. Here, clinical study results published since 2008 for patients with relapsed/refractory MCL were reviewed to compare available evidence for treatment guidance. Most trials identified were non-randomized, phase II studies performed at a limited number of sites, and many evaluated MCL as one of multiple non-Hodgkin lymphoma subtypes. Additional randomized, comparative trials are needed. Treatment selection generally depends on patient need, age and fitness, time of relapse, and line of therapy. Combination regimens typically produce higher response rates than single agents, and adding rituximab generally improves outcomes. The inclusion of ibrutinib, lenalidomide, temsirolimus, and bortezomib, represents an important advance for patients ineligible for, unable to tolerate, or failing high-intensity combination chemotherapy. A high need for effective treatments in relapsed/refractory MCL remains, particularly for elderly and frail patients.
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| 8. |
- Fuchs, David, et al.
(författare)
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Scoring the Risk of Having Systemic Mastocytosis in Adult Patients with Mastocytosis in the Skin
- 2021
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 2213-2198 .- 2213-2201. ; 9:4, s. 1705-1712.e4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mastocytosis in adults often presents with skin lesions. A bone marrow biopsy is necessary to confirm or exclude the presence of systemic mastocytosis (SM) in these cases. When a bone marrow biopsy is not performed, the provisional diagnosis is mastocytosis in the skin (MIS). No generally accepted scoring system has been established to estimate the risk of SM in these patients. OBJECTIVE: To develop a risk score to predict SM in adults with MIS. METHODS: We examined 1145 patients with MIS from the European Competence Network on Mastocytosis Registry who underwent a bone marrow biopsy. A total of 944 patients had SM and 201 patients had cutaneous mastocytosis; 63.7% were female, and 36.3% were male. Median age was 44 +/- 13.3 years. The median serum tryptase level amounted to 29.3 +/- 81.9 ng/mL. We established a multivariate regression model using the whole population of patients as a training and validation set (bootstrapping). A risk score was developed and validated with receiver-operating curves. RESULTS: In the multivariate model, the tryptase level (P < .001), constitutional/cardiovascular symptoms (P = .014), and bone symptoms/osteoporosis (P < .001) were independent predictors of SM (P < .001; sensitivity, 90.7%; specificity, 69.1%). A 6-point risk score was established (risk, 10.7%-98.0%) and validated. CONCLUSIONS: Using a large data set of the European Competence Network on Mastocytosis Registry, we created a risk score to predict the presence of SM in patients with MIS. Although the score will need further validation in independent cohorts, our score seems to discriminate safely between patients with SM and with pure cutaneous mastocytosis. (C) 2020 American Academy of Allergy, Asthma & Immunology
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| 9. |
- Hartmann, Karin, et al.
(författare)
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Cutaneous manifestations in patients with mastocytosis : Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology
- 2016
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 137:1, s. 35-45
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Tidskriftsartikel (refereegranskat)abstract
- Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma.
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| 10. |
- Kennedy, Vanessa E., et al.
(författare)
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Mast cell leukemia : clinical and molecular features and survival outcomes of patients in the ECNM Registry
- 2023
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:9, s. 1713-1724
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Tidskriftsartikel (refereegranskat)abstract
- Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis defined by >= 20% mast cells (MC) on a bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network on Mastocytosis registry. Thirty-one (34%) patients had a diagnosis of MCL with an associated hematologic neoplasm (MCL-AHN). Chronic MCL (lack of C-findings) comprised 14% of patients, and only 4.5% had "leukemic MCL" (>= 10% circulating MCs). KIT D816V was found in 62/85 (73%) evaluable patients; 9 (11%) individuals exhibited alternative KIT mutations, and no KIT variants were detected in 14 (17%) subjects. Ten evaluable patients (17%) had an abnormal karyotype and the poor-risk SRSF2, ASXL1, and RUNX1 (S/A/R) mutations were identified in 16/36 (44%) patients who underwent next-generation sequencing. Midostaurin was the most common therapy administered to 65% of patients and 45% as first-line therapy. The median overall survival (OS) was 1.6 years. In multivariate analysis (S/A/R mutations excluded owing to low event rates), a diagnosis of MCL-AHN (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.7-13.0; P = .001) and abnormal karyotype (HR, 5.6; 95% CI, 1.4-13.3; P = .02) were associated with inferior OS; KIT D816V positivity (HR, 0.33; 95% CI, 0.11-0.98; P = .04) and midostaurin treatment (HR, 0.32; 95% CI, 0.08-0.72; P = .008) were associated with superior OS. These data provide the most comprehensive snapshot of the clinicopathologic, molecular, and treatment landscape of MCL to date, and should help further inform subtyping and prognostication of MCL.
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| 11. |
- Kluin-Nelemans, Hanneke C., et al.
(författare)
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Cytogenetic and molecular aberrations and worse outcome for male patients in systemic mastocytosis
- 2021
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Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 11:1, s. 292-303
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Tidskriftsartikel (refereegranskat)abstract
- In systemic mastocytosis (SM), the clinical features and survival vary greatly. Patient-related factors determining the outcome in SM are largely unknown. Methods: We examined the impact of sex on the clinical features, progression-free survival (PFS), and overall survival (OS) in 3403 patients with mastocytosis collected in the registry of the European Competence Network on Mastocytosis (ECNM). The impact of cytogenetic and molecular genetic aberrations on sex differences was analyzed in a subset of patients. Results: Of all patients enrolled, 55.3% were females. However, a male predominance was found in a subset of advanced SM (AdvSM) patients, namely SM with an associated hematologic neoplasm (SM-AHN, 70%; p < 0.001). Correspondingly, organomegaly (male: 23% vs. female: 13%, p = 0.007) was more, whereas skin involvement (male: 71% vs. female: 86%, p = 0.001) was less frequent in males. In all patients together, OS (p < 0.0001) was significantly inferior in males, and also within the WHO sub-categories indolent SM, aggressive SM (ASM) and SM-AHN. PFS was significantly (p = 0.0002) worse in males when all patients were grouped together; due to low numbers of events, this significance persisted only in the subcategory smoldering SM. Finally, prognostically relevant cytogenetic abnormalities (10% vs. 5%, p = 0.006) or molecular aberrations (SRSF2/ASXLI/RUNXI profile; 63% vs. 40%, p = 0.003) were more frequently present in males. Conclusions: Male sex has a major impact on clinical features, disease progression, and survival in mastocytosis. Male patients have an inferior survival, which seems related to the fact that they more frequently develop a multi-mutated AdvSM associated with a high-risk molecular background.
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| 12. |
- Lévy, Romain, et al.
(författare)
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Human CARMIL2 deficiency underlies a broader immunological and clinical phenotype than CD28 deficiency.
- 2023
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 220:2
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Tidskriftsartikel (refereegranskat)abstract
- Patients with inherited CARMIL2 or CD28 deficiency have defective T cell CD28 signaling, but their immunological and clinical phenotypes remain largely unknown. We show that only one of three CARMIL2 isoforms is produced and functional across leukocyte subsets. Tested mutant CARMIL2 alleles from 89 patients and 52 families impair canonical NF-κB but not AP-1 and NFAT activation in T cells stimulated via CD28. Like CD28-deficient patients, CARMIL2-deficient patients display recalcitrant warts and low blood counts of CD4+ and CD8+ memory T cells and CD4+ TREGs. Unlike CD28-deficient patients, they have low counts of NK cells and memory B cells, and their antibody responses are weak. CARMIL2 deficiency is fully penetrant by the age of 10 yr and is characterized by numerous infections, EBV+ smooth muscle tumors, and mucocutaneous inflammation, including inflammatory bowel disease. Patients with somatic reversions of a mutant allele in CD4+ T cells have milder phenotypes. Our study suggests that CARMIL2 governs immunological pathways beyond CD28.
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| 13. |
- Lübke, Johannes, et al.
(författare)
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Prognostic Impact of Organomegaly in Mastocytosis : An Analysis of the European Competence Network on Mastocytosis
- 2023
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 2213-2198 .- 2213-2201. ; 11:2, s. 581-590
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Organomegaly, including splenomegaly, hepatomegaly, and/or lymphadenopathy, are important diagnostic and prognostic features in patients with cutaneous mastocytosis (CM) or systemic mastocytosis (SM).OBJECTIVES: To investigate the prevalence and prognostic impact of 1 or more organomegalies on clinical course and survival in patients with CM/SM.METHODS: Therefore, 3155 patients with CM (n = 1002 [32%]) or SM (n = 2153 [68%]) enrolled within the registry of the European Competence Network on Mastocytosis were analyzed. RESULTS: Overall survival (OS) was adversely affected by the number of organomegalies (OS: #0 vs #1 hazard ratio [HR], 4.9; 95% CI, 3.4-7.1, P < .001; #1 vs #2 HR, 2.1, 95% CI, 1.4-3.1, P < .001; #2 vs #3 HR, 1.7, 95% CI, 1.2-2.5, P = .004). Lymphadenopathy was frequently detected in patients with smoldering SM (SSM, 18 of 60 [30%]) or advanced SM (AdvSM, 137 of 344 [40%]). Its presence confered an inferior outcome in patients with AdvSM compared with patients with AdvSM without lymphadenopathy (median OS, 3.8 vs 2.6 years; HR, 1.6; 95% CI, 1.2-2.2; P = .003). OS was not different between patients having organomegaly with either ISM or SSM (median, 25.5 years vs not reached; P = .435). At time of disease progression, a new occurrence of any organomegaly was observed in 17 of 40 (43%) patients with ISM, 4 of 10 (40%) patients with SSM, and 33 of 86 (38%) patients with AdvSM, respectively.CONCLUSIONS: Organomegalies including lymphadenopathy are often found in SSM and AdvSM. ISM with organomegaly has a similar course and prognosis compared with SSM. The number of organomegalies is adversely associated with OS. A new occurrence of organomegaly in all variants of SM may indicate disease progression.
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| 14. |
- Manry, Jérémy, et al.
(författare)
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The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 119:21
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Tidskriftsartikel (refereegranskat)abstract
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼1% of individuals aged <70 y and in >4% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRDs were 17.0 (95% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and ≥70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17% (0.12 to 0.31) for individuals <40 y old to 26.7% (20.3 to 35.2) for those ≥80 y old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84% (0.31 to 8.28) to 40.5% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-α2 and IFN-ω. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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| 15. |
- Sperr, Wolfgang R., et al.
(författare)
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International prognostic scoring system for mastocytosis (IPSM) : a retrospective cohort study
- 2019
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Ingår i: The Lancet Haematology. - : ELSEVIER SCI LTD. - 2352-3026. ; 6:12, s. E638-E649
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Tidskriftsartikel (refereegranskat)abstract
- 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<0.0001). For patients with non-advanced mastocytosis (n=1380), we identified age 60 years or older (HR 10.75, 95% CI 5.68-20.32) and a concentration of alkaline phosphatase 100 U/L or higher (2.91, 1.60-5.30) as additional independent prognostic variables for overall survival. The resulting scoring system divided patients with non-advanced mastocytosis into three groups: low (no risk factors), intermediate 1 (one risk factor), and intermediate 2 (two risk factors). Overall survival and progression-free survival differed significantly among these groups (p<0.0001). In patients with advanced mastocytosis (n=259), age 60 years or older (HR 2.14, 95% CI 1.42-3.22), a concentration of tryptase 125 ng/mL or higher (1.81, 1.20-2.75), a leukocyte count of 16 x 10(9) per L or higher (1.88, 1.27-2.79), haemoglobin of 11 g/dL or lower (1.71, 1.13-2.57), a platelet count of 100 x 10(9) per L or lower (1.63, 1.13-2.34), and skin involvement (0.46, 0.30-0.69) were prognostic variables. Based on these variables, a separate score for advanced mastocytosis with four risk categories was established, with significantly different outcomes for overall survival and progression-free survival (p<0.0001). The prognostic value of both scores was confirmed in 413 patients with non-advanced disease and 49 with advanced mastocytosis from the validation cohort. 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. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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| 16. |
- Trizuljak, Jakub, et al.
(författare)
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Clinical features and survival of patients with indolent systemic mastocytosis defined by the updated WHO classification
- 2020
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 75:8, s. 1927-1938
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Tidskriftsartikel (refereegranskat)abstract
- Background: In indolent systemic mastocytosis (ISM), several risk factors of disease progression have been identified. Previous studies, performed with limited patient numbers, have also shown that the clinical course in ISM is stable and comparable to that of cutaneous mastocytosis (CM). The aim of this project was to compare the prognosis of patients with ISM with that of patients with CM.Methods: We employed a dataset of 1993 patients from the registry of the European Competence Network on Mastocytosis (ECNM) to compare outcomes of ISM and CM.Results: We found that overall survival (OS) is worse in ISM compared to CM. Moreover, in patients with typical ISM, bone marrow mastocytosis (BMM), and smoldering SM (SSM), 4.1% of disease progressions have been observed (4.9% of progressions in typical ISM group, 1.7% in BMM, and 9.4% in SSM). Progressions to advanced SM were observed in 2.9% of these patients. In contrast, six patients with CM (1.7%) converted to ISM and no definitive progression to advanced SM was found. No significant differences in OS and event-free survival (EFS) were found when comparing ISM, BMM, and SSM. Higher risk of both progression and death was significantly associated with male gender, worse performance status, and organomegaly.Conclusion: Our data confirm the clinical impact of the WHO classification that separates ISM from CM and from other SM variants.
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| 17. |
- Ustun, Celalettin, et al.
(författare)
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Hematopoietic stem-cell transplantation for advanced systemic mastocytosis
- 2014
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 32:29, s. 3264-3274
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown.PATIENTS AND METHODS: In a global effort to define the value of HCT in SM, 57 patients with the following subtypes of SM were evaluated: SM associated with clonal hematologic non-mast cell disorders (SM-AHNMD; n = 38), mast cell leukemia (MCL; n = 12), and aggressive SM (ASM; n = 7). Median age of patients was 46 years (range, 11 to 67 years). Donors were HLA-identical (n = 34), unrelated (n = 17), umbilical cord blood (n = 2), HLA-haploidentical (n = 1), or unknown (n = 3). Thirty-six patients received myeloablative conditioning (MAC), and 21 patients received reduced-intensity conditioning (RIC).RESULTS: Responses in SM were observed in 40 patients (70%), with complete remission in 16 patients (28%). Twelve patients (21%) had stable disease, and five patients (9%) had primary refractory disease. Overall survival (OS) at 3 years was 57% for all patients, 74% for patients with SM-AHNMD, 43% for those with ASM, and 17% for those with MCL. The strongest risk factor for poor OS was MCL. Survival was also lower in patients receiving RIC compared with MAC and in patients having progression compared with patients having stable disease or response.CONCLUSION: AlloHCT was associated with long-term survival in patients with advanced SM. Although alloHCT may be considered as a viable and potentially curative therapeutic option for advanced SM in the meantime, given that this is a retrospective analysis with no control group, the definitive role of alloHCT will need to be determined by a prospective trial.
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| 18. |
- Valent, Peter, et al.
(författare)
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Advances in the Classification and Treatment of Mastocytosis : Current Status and Outlook toward the Future.
- 2017
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Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 77:6, s. 1261-1270
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 19. |
- Valent, Peter, et al.
(författare)
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European Competence Network on Mastocytosis (ECNM) : 10-year jubilee, update, and future perspectives
- 2012
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Ingår i: Wiener Klinische Wochenschrift. - : Springer Science and Business Media LLC. - 0043-5325 .- 1613-7671. ; 124:23-24, s. 807-814
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Tidskriftsartikel (refereegranskat)abstract
- The European Competence Network on Mastocytosis (ECNM) was initiated in 2002 as a multidisciplinary and multinational cooperative approach to increase awareness and to improve diagnosis and therapy of mastocytosis. The network is composed of local centers, physicians, and scientists who have dedicated their work to patients with mastocytosis. A strategic goal of the ECNM is to provide the best available information about the disease to patients and physicians. During the past 10 years, the ECNM has expanded to various countries and contributed successfully to the development of markers, definitions, and standards in the field of mastocytosis. Members of the ECNM organized Annual Meetings in Europe and two Working Conferences on Mastocytosis in Vienna (in 2005 and 2010), and initiated and supported several preclinical and clinical trials. In all these activities, representatives of the ECNM cooperate closely with their US colleagues, with patient-organizations in Europe and in the USA, and with other scientific networks. The ECNM also launched a mastocytosis registry that has been activated in 2012. Using the central database of this registry, cooperative multicenter studies, which should include sufficient numbers of patients and robust evaluations, will be conducted. These studies will increase our knowledge about optimal management and therapy of patients with mastocytosis in the future.
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| 20. |
- Valent, Peter, et al.
(författare)
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European Competence Network on Mastocytosis (ECNM) : 20-Year Jubilee, Updates, and Future Perspectives
- 2023
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 2213-2198 .- 2213-2201. ; 11:6, s. 1706-1717
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Tidskriftsartikel (refereegranskat)abstract
- In 2002, the European Competence Network on Mastocytosis (ECNM) was launched as a multidisciplinary collaborative initiative to increase the awareness and to improve diagnosis and management of patients with mast cell (MC) disorders. The ECNM consists of a net of specialized centers, expert physicians, and scientists who dedicate their work to MC diseases. One essential aim of the ECNM is to timely distribute all available information about the disease to patients, doctors, and scientists. In the past 20 years, the ECNM has expanded substantially and contributed successfully to the development of new diagnostic concepts, and to the classification, prognostication, and treatments of patients with mastocytosis and MC activation disorders.
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| 21. |
- Wang, Michael L., et al.
(författare)
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Ibrutinib plus Bendamustine and Rituximab in Untreated Mantle-Cell Lymphoma
- 2022
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 386:26, s. 2482-2494
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Ibrutinib, a Bruton's tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by rituximab maintenance therapy in older patients with untreated mantle-cell lymphoma. METHODS We randomly assigned patients 65 years of age or older to receive ibrutinib (560 mg, administered orally once daily until disease progression or unacceptable toxic effects) or placebo, plus six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients with an objective response (complete or partial response) received rituximab maintenance therapy, administered every 8 weeks for up to 12 additional doses. The primary end point was progression-free survival as assessed by the investigators. Overall survival and safety were also assessed. RESULTS Among 523 patients, 261 were randomly assigned to receive ibrutinib and 262 to receive placebo. At a median follow-up of 84.7 months, the median progression-free survival was 80.6 months in the ibrutinib group and 52.9 months in the placebo group (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P=0.01). The percentage of patients with a complete response was 65.5% in the ibrutinib group and 57.6% in the placebo group (P=0.06). Overall survival was similar in the two groups. The incidence of grade 3 or 4 adverse events during treatment was 81.5% in the ibrutinib group and 77.3% in the placebo group. CONCLUSIONS Ibrutinib treatment in combination with standard chemoimmunotherapy significantly prolonged progression-free survival. The safety profile of the combined therapy was consistent with the known profiles of the individual drugs.
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| 22. |
- Zanotti, Roberta, et al.
(författare)
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Refined diagnostic criteria for bone marrow mastocytosis : a proposal of the European competence network on mastocytosis
- 2022
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Ingår i: Leukemia. - : Springer Nature. - 0887-6924 .- 1476-5551. ; 36:2, s. 516-524
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Tidskriftsartikel (refereegranskat)abstract
- In the current classification of the World Health Organization (WHO), bone marrow mastocytosis (BMM) is a provisional variant of indolent systemic mastocytosis (ISM) defined by bone marrow involvement and absence of skin lesions. However, no additional diagnostic criteria for BMM have been proposed. Within the registry dataset of the European Competence Network on Mastocytosis, we compared characteristics and outcomes of 390 patients with BMM and 1175 patients with typical ISM. BMM patients were significantly older, predominantly male, had lower tryptase and lower burden of neoplastic mast cells, and displayed a higher frequency of allergic reactions, mainly triggered by Hymenoptera, than patients with typical ISM. The estimated 10-year progression-free survival of BMM and typical ISM was 95.9% and 92.6%, respectively. In BMM patients defined by WHO-based criteria, the presence of one B-Finding and tryptase level >= 125 ng/mL were identified as risk factors for progression in multivariate analyses. BMM patients without any of these risk factors were found to have better progression-free survival (p < 0.05) and better overall survival (p < 0.05) than other ISM patients. These data support the proposal to define BMM as a separate SM variant characterized by SM criteria, absence of skin lesions, absence of B-Findings, and tryptase levels <125 ng/mL.
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