Allogeneic haematopoietic cell transplantation for advanced systemic mastocytosis: Best practice recommendations on behalf of the EBMT Practice Harmonisation and Guidelines Committee.

Systemic Mastocytosis (SM) is a multifaceted clinically heterogeneous disease. Advanced SM (AdvSM) comprises three entities: aggressive SM (ASM), mast cell leukaemia (MCL) and SM with an associated hematologic neoplasm (SM-AHN), the latter accounting for 60-70% of all AdvSM cases. Detection of a disease-triggering mutation in the KIT gene (esp.

Case Report: A family history of peanut allergy and hereditary alpha-tryptasemia.

Context: Hereditary alpha-tryptasemia (HαT) is associated with elevated basal serum tryptase (bST) and is associated with a higher risk of severe anaphylactic reactions in patients with clonal mast cell disorders or IgE-mediated Hymenoptera venom-induced anaphylaxis. The consequence of this genetic trait remains to be determined in other allergic diseases and food allergy in particular.

Objectives: Here, we describe three cases of peanut allergy among siblings from a single family of four: two of them were associated with HαT, and the third one was associated with the tryptase wild-type genotype.

Antibody-Based and Cell Therapies for Advanced Mastocytosis: Established and Novel Concepts.

Advanced systemic mastocytosis (SM) is a heterogeneous group of myeloid neoplasms characterized by an uncontrolled expansion of mast cells (MC) in one or more internal organs, SM-induced tissue damage, and poor prognosis. Advanced SM can be categorized into aggressive SM (ASM), MC leukemia (MCL), and SM with an associated hematologic neoplasm (SM-AHN). In a vast majority of all patients, neoplastic cells display a mutation, mostly D816V and rarely other variants.

The Normal Range of Baseline Tryptase Should Be 1 to 15 ng/mL and Covers Healthy Individuals With HαT.

Physiological levels of basal serum tryptase vary among healthy individuals, depending on the numbers of mast cells, basal secretion rate, copy numbers of the TPSAB1 gene encoding alpha tryptase, and renal function. Recently, there has been a growing debate about the normal range of tryptase because individuals with the hereditary alpha tryptasemia (HαT) trait may or may not be symptomatic, and if symptomatic, uncertainty exists as to whether this trait directly causes clinical phenotypes or aggravates certain conditions. In fact, most HαT-positive cases are regarded as asymptomatic concerning mast cell activation.

Histamine elevation in familial Mediterranean fever: A study from the Juvenile Inflammatory Rheumatism cohort.

Background: Familial Mediterranean Fever (FMF) is the most frequent monogenic autoinflammatory disease (AID). Some patients have persistent symptoms despite colchicine intake. Mast cells (MC) are innate immune cells involved in inflammatory conditions including AID.

European Competence Network on Mastocytosis (ECNM): 20-Year Jubilee, Updates, and Future Perspectives.

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.

Mast cell leukemia: clinical and molecular features and survival outcomes of patients in the ECNM Registry.

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).

Mast Cell Diseases in Practice and Research: Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond.

Background: Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes.

Objective: This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patients' quality of life by addressing unmet needs.

Refined Treatment Response Criteria for Indolent Systemic Mastocytosis Proposed by the ECNM-AIM Consortium.

Indolent systemic mastocytosis (ISM) has a favorable prognosis and normal life expectancy. However, many patients suffer from mast cell (MC) mediator-related symptoms, which significantly affect quality of life (QoL). Cutaneous, gastrointestinal, and neurological complaints, musculoskeletal pain, and the presence of skin lesions, anaphylaxis, and osteoporosis are the main symptoms and signs in ISM and must be assessed in all patients before and during treatment.

Standards of Pathology in the Diagnosis of Systemic Mastocytosis: Recommendations of the EU-US Cooperative Group.

Pathology plays a central role in the diagnosis of systemic mastocytosis (SM), its delineation from other neoplasms and reactive conditions, and in monitoring of SM under therapy. The morphologic hallmark of SM is the accumulation of spindle-shaped, hypogranulated mast cells (MCs) in bone marrow (BM) and other extracutaneous tissues. Four of the 5 World Health Organization-defined diagnostic criteria (ie, compact MC aggregates [=major criterion]; atypical MC morphology; activating KIT point mutations; aberrant expression of CD25 and/or CD2 and/or CD30 in MCs [=minor criteria]) can be addressed by the pathologist.

Proposed European Competence Network on Mastocytosis-American Initiative in Mast Cell Diseases (ECNM-AIM) Response Criteria in Advanced Systemic Mastocytosis.

Advanced systemic mastocytosis (AdvSM) is characterized by the presence of KIT D816V and other somatic mutations (eg, in SRSF2, ASXL1, and RUNX1) in 95% and 60% to 70% of patients, respectively. The biological and clinical consequences of AdvSM include multilineage involvement (eg, associated hematologic neoplasm) in 60% to 80% of patients, variable infiltration and damage (C-findings) of predominantly bone marrow and visceral organs through affected mast cell (MC) and non-MC lineages, and elevated levels of serum tryptase. Recently, the treatment landscape has substantially changed with the introduction of the multikinase/KIT inhibitor midostaurin and the selective KIT D816V inhibitor avapritinib.

Global Classification of Mast Cell Activation Disorders: An ICD-10-CM-Adjusted Proposal of the ECNM-AIM Consortium.

Mast cell activation (MCA) is common and occurs in a number of pathologic conditions, including IgE-dependent and independent allergic reactions, atopic disorders, autoimmune processes, and mastocytosis. In a subset of patients, no underlying disease and no known trigger of MCA are found. When the symptoms are severe, systemic, and recurrent, and accompanied by a diagnostic increase in the serum tryptase level or other mast cell mediators, an MCA syndrome (MCAS) may be diagnosed.

Clinical impact and proposed application of molecular markers, genetic variants, and cytogenetic analysis in mast cell neoplasms: Status 2022.

Mast cell neoplasms are an emerging challenge in the fields of internal medicine, allergy, immunology, dermatology, laboratory medicine, and pathology. In this review, we discuss the current standards for the diagnosis and prognostication of mast cell neoplasms with special reference to clinically relevant germline and somatic gene variants. In patients with cutaneous mastocytosis or with indolent systemic mastocytosis (SM), various KIT-activating mutations act as key molecular drivers of the disease.

Personalized Management Strategies in Mast Cell Disorders: ECNM-AIM User's Guide for Daily Clinical Practice.

Mastocytosis is a myeloid neoplasm defined by expansion and focal accumulation of clonal mast cells (MCs) in one or more organs. The disease exhibits a complex pathology and may be complicated by MC activation, bone abnormalities, neurological problems, gastrointestinal symptoms, and/or hematologic progression. The World Health Organization divides mastocytosis into cutaneous forms, systemic mastocytosis (SM) and MC sarcoma.

Standards of Genetic Testing in the Diagnosis and Prognostication of Systemic Mastocytosis in 2022: Recommendations of the EU-US Cooperative Group.

Mastocytosis comprises rare heterogeneous diseases characterized by an increased accumulation of abnormal mast cells in various organs/tissues. The pathogenesis of mastocytosis is strongly linked to the presence of KIT-activating mutations. In systemic mastocytosis (SM), the most frequent mutation encountered is KIT p.

Updated Diagnostic Criteria and Classification of Mast Cell Disorders: A Consensus Proposal.

Mastocytosis is a hematologic neoplasm characterized by expansion and focal accumulation of neoplastic mast cells (MC) in diverse organs, including the skin, bone marrow (BM), spleen, liver, and gastrointestinal tract. The World Health Organization classification divides the disease into prognostically distinct variants of cutaneous mastocytosis (CM) and systemic mastocytosis (SM). Although this classification remains valid, recent developments in the field and the advent of new diagnostic and prognostic parameters created a need to update and refine definitions and diagnostic criteria in MC neoplasms.

Establishing diagnostic criteria for mastocytosis in skin biopsies.

Aims: The diagnosis of mastocytosis in skin biopsies can be challenging - particularly in cases with very few mast cells. More diagnostic criteria are needed.

Methods And Results: We analyzed 103 skin biopsies from patients with mastocytosis and compared them with biopsies from inflammatory skin lesions and normal skin.

Refined diagnostic criteria for bone marrow mastocytosis: a proposal of the European competence network on mastocytosis.

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.

The association of Greig syndrome and mastocytosis reveals the involvement of the hedgehog pathway in advanced mastocytosis.

Mastocytosis is a heterogeneous disease characterized by an abnormal accumulation of mast cells (MCs) in 1 or several organs. Although a somatic KIT D816V mutation is detected in ∼85% of patients, attempts to demonstrate its oncogenic effect alone have repeatedly failed, suggesting that additional pathways are involved in MC transformation. From 3 children presenting with both Greig cephalopolysyndactyly syndrome (GCPS, Mendelian Inheritance in Man [175700]) and congenital mastocytosis, we demonstrated the involvement of the hedgehog (Hh) pathway in mastocytosis.

The pathogenic role of c-Kit+ mast cells in the spinal motor neuron-vascular niche in ALS.

Degeneration of motor neurons, glial cell reactivity, and vascular alterations in the CNS are important neuropathological features of amyotrophic lateral sclerosis (ALS). Immune cells trafficking from the blood also infiltrate the affected CNS parenchyma and contribute to neuroinflammation. Mast cells (MCs) are hematopoietic-derived immune cells whose precursors differentiate upon migration into tissues.

Selecting the Right Criteria and Proper Classification to Diagnose Mast Cell Activation Syndromes: A Critical Review.

In recent years, knowledge about mechanisms underlying mast cell activation (MCA) and accumulation in various pathologic conditions increased substantially. In addition, criteria and a classification of MCA syndromes (MCASs) have been set forth. MCAS is defined by typical clinical symptoms, a substantial increase in serum tryptase level during an attack over the patient's baseline tryptase, and a response of the symptoms to drugs targeting mast cells, mediator production, and/or mediator effects.