Autoimmune polyendocrine syndrome and thrombocytosis

We describe a woman aged 37 years, affected with Hashimoto's thyroiditis, detected since the age of 17, with gonadic insufficiency with anti-ovarian antibodies since the age of 22 years and Addison's disease since 24 years old. At that moment, the diagnosis of autoimmune polyendocrine syndrome (APS) was made. Concomitant to this diagnosis, thrombocytosis was detected and aetiological assessment revealed an atrophy of the spleen. Differential diagnoses of APS and hyposplenism will be discussed. We will look at a possible association between these two pathologies. Indeed, asplenism is found in approximately 20% of adults affected by type 1 APS, also called auto-immune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome. The most likely aetiology for this atrophy of the spleen is a destruction of auto-immunological origin. However, in our patient, the search for a mutation of the autoimmune regulator (AIRE) gene proved negative. This mutation is commonly, but not systematically, present in type 1 APS. A type 2 APS should then be considered.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Targeted treatment options in mastocytosis

Mastocytosis refers to a heterogeneous group of disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin (cutaneous mastocytosis when only in the skin, CM) or in various organs (systemic mastocytosis, SM). This leads to a wide variety of clinical manifestations resulting from excessive mediator release in CM and benign forms of SM (indolent SM, ISM) and from tissue mast cell infiltration causing multiorgan dysfunction and failure in more aggressive subtypes (aggressive SM, ASM, or mast cell leukemia). In addition, SM may be associated with hematological neoplasms (AHN). While treatment of ISM primarily aims at symptom management with anti-mediator therapies, cytoreductive and targeted therapies are needed to control the expansion of neoplastic mast cells in advanced forms of SM, in order to improve overall survival. Mast cell accumulation results from a gain-of-function mutation (mostly the D816V mutation) within the KIT tyrosine kinase domain expressed by mast cells and additional genetic and epigenetic mutations may further determine the features of the disease (ASM and AHN). Consequently, tyrosine kinase inhibitors and targeted therapies directed against the oncogenic signaling machinery downstream of KIT are attractive therapeutic approaches. A better understanding of the relative contribution of these genetic and epigenetic events to the molecular pathogenesis of mastocytosis is of particular interest for the development of targeted therapies and therefore to better choose patient subgroups that would best benefit from a given therapeutic strategy.SCOPUS: re.jinfo:eu-repo/semantics/publishe

La mastocytose: une maladie revisitée a la lumière des nouvelles données génétiques.

Mastocytosis is a heterogenous disorder due to abnormal proliferation and infiltration of mast cells in different tissues, primarily the skin and the bone marrow. Cutaneous mastocytosis is often benign and regresses spontaneously. Systemic mastocytosis is a chronic disease in which some types are indolent but other types such as mast cell leukemia are very aggressive. Pathogenesis of systemic mastocytosis involves a somatic mutation of the gene coding for the c-kit receptor, the most frequent mutation being D816V. Diagnostic criteria have been established by the WHO using histopathological, molecular and biochemical parameters. Treatment of systemic mastocytosis remains a challenge for the clinician due to variability and complexity of the disease. There is, in addition, a lack of a standard and efficient treatment. New targeted therapies with tyrosine kinase inhibitors directed against the c-kit receptor are currently being studied, with the purpose to act specifically on the " primum movens "of the disease. The current review provides an overview of pathogenesis, clinical presentation, diagnosis and classification of cutaneous and systemic mastocytosis. We also discuss the prognosis and the different treatments currently available according to the sub-type of mastocytosis.English AbstractJournal ArticleReviewSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Campath-1H: a highly effective therapy in T-cell prolymphocytic leukemia

info:eu-repo/semantics/nonPublishe

Low-density lipoprotein oxidation by myeloperoxidase occurs in the blood circulation during haemodialysis

info:eu-repo/semantics/publishe

Therapeutic drug monitoring of posaconazole in patients with acute myeloid leukemia or myelodysplastic syndrome

Posaconazole is a broad-spectrum triazole antifungal available as an oral suspension. Pharmacokinetic data showed a high variability of plasma posaconazole concentrations (PPCs) in patients, suggesting a potential interest in drug monitoring. The aim of our prospective study was to measure the PPCs in prophylactically treated patients to evaluate the impact of different factors on these concentrations. In 40 patients treated prophylactically with posaconazole for acute myeloid leukemia or myelodysplastic syndrome between February 2009 and August 2010, PPCs were measured at day 7 of treatment and then twice weekly. Demographic data, clinical data (including gastrointestinal disorders, comedications, and treatment compliance), caloric and fat intake, and biological data were collected and evaluated. We obtained 275 measurements of PPCs, with a median of 430 ng/ml. PPCs were significantly lower in patients with mucositis (P < 0.001), nausea (P = 0.03), diarrhea (P = 0.03), or vomiting (P = 0.05). PPCs were higher in patients with a higher caloric intake (P = 0.02), while the proportion of fat intake had no influence on PPCs (P = 0.84). The concomitant use of proton pump inhibitors decreased the PPCs (P = 0.02), while the use of tacrolimus increased the PPC (P = 0.03). In the multivariate analysis, the factors influencing the PPCs independently were the concomitant use of tacrolimus (P < 0.001), the presence of mucositis (P = 0.01), and food intake (P = 0.02). Our study confirmed the high variability of posaconazole bioavailability and showed the significant influence of gastrointestinal disorders, food intake, and concomitant medication on the PPCs. However, the optimal PPCs still remain to be defined and correlated with clinical efficacy. Copyright © 2012, American Society for Microbiology. All Rights Reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

The pleiotropic effect of statins in haemodialysis patients is not the consequence of an inhibition of LDL oxidation by myeloperoxidase.

Comparative StudyLetterinfo:eu-repo/semantics/publishe

Acute Myeoloid Leukemia in the elderly: Role of age and cytogenetic data in the outcome of fit patients

info:eu-repo/semantics/nonPublishe

Safety and Efficacy of Radioimmunotherapy with 90Yttrium-rituximab in Patients with Relapsed CD20+ B cell Lymphoma: A Feasibility Study

info:eu-repo/semantics/publishe

Compass : a prospective study comparing clinical evaluation with different geriatric screening methods in newly diagnosed elderly multiple myeloma patients

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