Symptoms and General Pathology

All Conditions

Neoplasms

Immune System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Syndrome

Mastocytosis

Urticaria

Mast Cell Activation Syndrome

Mast Cell Activation Disorders

Urticaria Pigmentosa

Skin Diseases

Skin Diseases, Vascular

Hypersensitivity

Hypersensitivity, Immediate

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Mastocytosis, Cutaneous

Skin Neoplasms

Pigmentation Disorders

Participants affected by cutaneous and systemic mastocytosis with or without eye disabilities

Eye examination :

Ocular tonometry to determine intraocular pressure Refraction assessment Retina examination Slit lamp examination Visual acuity Schirmer's test Corneal topography Funduscopic examination Optical coherence tomography

Ophthalmological examination

Mastocytosis is a rare condition characterized by an accumulation of mast cell cells in one or more organs such as the liver, bone marrow, spleen and intestines. Its prevalence in the general population is 1 in 10,000.

This pathology is due to the proliferation of a mast cell clone and the excessive release of inflammatory mediators which lead to abnormal tissue infiltration.

To date, there are only a few cases reporting ocular and orbital manifestations of mastocytosis.

Our prospective, interventional and single-center study consist in describing the ocular functional manifestations and ocular surface abnormalities of patients with systemic and cutaneous mastocytosis.

Patient with systemic or cutaneous mastocytosis will be included in the study. Data about organ involvement of mastocytosis will be collected. Participants will be screened with a medical and eye disease history. They will also have an eye exam.

Participants will provide a tears sample.

Ocular and Palpebral Manifestations of Mastocytosis (MOOMA)

Number of patients with functional complaints or abnormalities of the surface, orbit, anterior and posterior segment of the eyeball.

Details of functional complaints, abnormalities of various specialized examinations such as ocular tonometry to determine intraocular pressure, Refraction assessment, Retina examination, Slit lamp examination, Visual acuity, Schirmer's test, Corneal topography, Funduscopic examination, Optical coherence tomography

Significative association with a mastocytosis subtype or certain organ involvements or biological abnormalities

Poitiers University Hospital

Anaphylaxis

Observational study of all patients referred for suspected mast cell disease. Collection of blood or bone marrow for analysis during diagnostic procedures.

5-8 cc blood or bone marrow was additionally collected for analysis during diagnostic procedures. No assigned interventions.

Collection of blood and bone marrow

Cem Akin, M.D., Ph.D.

Mastocytosis is a disorder characterized by presence of excessive numbers of mast cells in skin, bone marrow and internal organs. It can affect both children and adults, males and females and individuals from all ethnic backgrounds, although precise demographic information about the affected populations is not available as it is a rare disorder. Mastocytosis in children is generally limited to the skin and follows a self limited course, while it is a disorder of the hematopoietic stem cell associated with somatic mutations of the c-kit gene in most patients with adult-onset of disease. There is no known curative therapy for most patients with systemic mastocytosis. Recent research studies identified several subtypes of disease with distinct clinical and pathologic features, however, a precise understanding of the incidence as well as molecular pathology of different disease subtypes is lacking. This study aims to examine molecular and cellular pathological aspects of disease in patients with mastocytosis and correlate findings with clinical presentation and prognosis. Patients will undergo a routine history and physical examination, and diagnostic tests will be ordered as dictated by each patient's clinical presentation. Blood and bone marrow will be obtained for diagnostic and research purposes. Genetic analysis of the c-kit gene regulating mast cell growth and differentiation will be performed. It is hoped that findings obtained from this study will help to design novel therapies for mastocytosis and other disorders in which mast cells play a critical role.

Molecular Mechanisms and Diagnosis of Mastocytosis

Investigation of Cellular and Molecular Pathologic Mechanisms in Mast Cell Disorders.

Patients were categorized into one of the clonal and non-clonal mast cell disorder categories after availability of diagnostic data

KIT D816V mutation was assessed in patient samples containing various proportions of neoplastic mast cells.

University of Michigan

Assistant Professor

Mastocytosis, Systemic

Systemic Mastocytosis

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Imatinib mesylate 300 or 400 mg daily for 12 months.

* In patients without B or C findings and without biological progression: 300 mg/24 h p.o during one year or until progression/unacceptable toxicity.
* In patients with B or C findings or biological progression: 300 mg/24 h p.o for two weeks and then 400 mg/24 h p.o for a total of one year of therapy, or until progression/unacceptable toxicity.

Luis Escribano, MD, PhD

The aim of this study is to evaluate the efficacy in terms of clinical and biological response rates of Imatinib Mesylate therapy in patients with systemic mastocytosis lacking KIT mutations.

In vitro studies have proven that imatinib inhibits wild type Kit (wtKit) and suppresses proliferation of the HMC-1V560G cell line, while it is ineffective on inhibiting the growth of HMC-1V560G, D816V cells. Apart from wtKit, Kit molecules carrying mutations in the extracellular, transmembrane and juxtamembrane domains, such as V560G, F522C and K509I, remain sensitive to imatinib. In contrast, several experiments have provided compelling evidence regarding the resistance against the growth-inhibitory effects of imatinib on cells carrying the D816V KIT mutation. As a consequence, sensitive and specific methods should be used in order to avoid "false" KIT mutation-negative cases and, for that purpose, mainly in cases with low bone marrow mast cell numbers, mutational studies should be performed using highly purified bone marrow mast cells by means of Facs sorting systems better than whole bone marrow, unsorted mononuclear cell fraction or mononuclear cell fraction pre-enriched using magnetic beads conjugated with anti-CD25 monoclonal antibody. In the present study mutational studies were performed in all cases in purified bone marrow mast cells (purity \> 97%) using a FACSaria system (Becton-Dickinson Biosciences) as previously described.

Patients without B or C findings according to the World Health Organization, and without features of biological progression of the disease receive oral Imatinib Mesylate 300 mg daily for up to 12 months or until clinical progression/unacceptable toxicity. Patients with B or C findings or biological progression initially receive oral Imatinib Mesylate 300 mg daily for two weeks; then, dose is increased up to 400 mg/day except in patients who develop hematological or any other dose-limiting toxicity.

Biological progression is defined as the presence of at least one of the following features: i) increased serum tryptase levels \> 200 ng/mL, ii) diffuse bone sclerosis, iii) patchy sclerosis with osteolysis and increased risk of bone fracture or significant bone pain, and, iv) organomegalies or lymph node enlargement due to mastocytosis.

Imatinib in KIT-negative Systemic Mastocytosis

Imatinib Mesylate Therapy in Systemic Mastocytosis Patients Lacking KIT Mutations

The grade of bone marrow infiltration is evaluated before and after 6 months of therapy by bone marrow histology and cytology, and flow cytometry performed on highly-purified bone marrow mast cells from patients with B or C findings

The grade of bone marrow infiltration is evaluated before and after 6 months of therapy by bone marrow histology and cytology, and flow cytometry performed on highly-purified bone marrow mast cells from patients without B or C findings, and from those with B or C findings who show response at the intermediate check-point (after 6 months of therapy)

Skin lesions are evaluated before and after therapy by macroscopic examination and skin biopsy.

Clinical symptoms such as pruritus, flushing, gastrointestinal symptoms and anaphylaxis are assessed before and after therapy using a clinical questionnaire that includes the type, frequency and severity of each symptom.

Organomegalies and adenomegalies are assessed before and after therapy by abdominal ultrasound.

Bone alterations are assessed before and after therapy by X-ray survey.

Genetic abnormalities are assessed before and after therapy by sequencyng analysis of the c-kit gene and the HUMARA assay.

Serum tryptase is measured before and after therapy.

The psychological impact of the disease and the quality of life of patients are evaluated before and after therapy by the Dermatology Life Quality Index.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ocular and Palpebral Manifestations of Mastocytosis (MOOMA)	NCT04978740	Mast Cell Activ... Mast Cell Activ... Mast Cell Disea... Urticaria Pigme...	Ophthalmologica...	18 Years -	Poitiers University Hospital
Molecular Mechanisms and Diagnosis of Mastocytosis	NCT00336076	Mastocytosis	Collection of b...	-	University of Michigan
Ocular and Palpebral Manifestations of Mastocytosis (MOOMA)	NCT04978740	Mast Cell Activ... Mast Cell Activ... Mast Cell Disea... Urticaria Pigme...	Ophthalmologica...	18 Years -	Poitiers University Hospital
Imatinib in KIT-negative Systemic Mastocytosis	NCT01297777	Systemic Mastoc...	Imatinib Mesyla...	18 Years -	Hospital Virgen de la Salud
Imatinib in KIT-negative Systemic Mastocytosis	NCT01297777	Systemic Mastoc...	Imatinib Mesyla...	18 Years -	Hospital Virgen de la Salud

Spots Global Cancer Trial Database for mast cell disease