Liquid chromatography-tandem mass spectrometry assay for therapeutic drug monitoring of the tyrosine kinase inhibitor, midostaurin, in plasma from patients with advanced systemic mastocytosis.

We developed and validated quantitative bioanalytical liquid chromatography-tandem mass spectrometry assay for the protein kinase inhibitor, midostaurin. Plasma samples were pre-treated using a protein precipitation with methanol containing midostaurin-d5 as an internal standard. After centrifugation, 5μL of the supernatant was injected into the chromatographic system.

Small intestinal CD4+ T-cell lymphoma is a heterogenous entity with common pathology features.

Background & Aims: Little is known about intestinal CD4+ T-cell lymphoma; this rare malignancy is misdiagnosed frequently. We evaluated diagnostic criteria and factors that might affect its development and outcome.

Methods: In a retrospective analysis, we analyzed medical records and intestinal specimens from 10 patients diagnosed with intestinal CD4+ T-cell lymphoma among 115 consecutive patients examined for severe enteropathy with villous atrophy.

HTLV-1-associated arthropathy treated with anti-TNF-alpha agent.

Human T cell leukemia virus type 1 or HTLV-1 infection is a public health problem in endemic regions like Japan, Central America or Africa. Although the majority of HTLV-1 carriers remain asymptomatic throughout their lives, some patients could develop neurological disorder, inflammatory arthropathy also called HTLV-1-associated arthropathy or T-cell malignancy, the adult T-cell leukemia/lymphoma or ATL with a very poor prognosis. Described to be very close to rheumatoid arthritis, HTLV-1-associated arthropathy patients have few or no response to the first line therapy with corticosteroids and disease modifying antirheumatic drugs or DMARDs.

Complex karyotype in mantle cell lymphoma is a strong prognostic factor for the time to treatment and overall survival, independent of the MCL international prognostic index.

Mantle cell lymphoma (MCL) is usually an aggressive disease. However, a few patients do have an "indolent" evolution (iMCL) defined by a long survival time without intensive therapy. Many studies highlight the prognostic role of additional genetic abnormalities, but these abnormalities are not routinely tested for and do not yet influence the treatment decision.

Management of mantle cell lymphoma in the elderly: current and potential strategies.

Mantle cell lymphoma is a distinct subtype of B-cell non-Hodgkin lymphoma, accounting for 3-10 % of all non-Hodgkin lymphoma cases. The median age at diagnosis is nearly 70 years. The prognosis of patients is based on the Mantle Cell Lymphoma International Prognostic Index, which is calculated on the basis of four independent prognostic factors (age, performance status, serum lactate dehydrogenase and leukocyte count).

The NF-κB pathway is rarely spontaneously activated in mantle cell lymphoma (MCL) cell lines and patient's samples.

In this study, we investigated the role of NF-κB (canonical and alternative pathways) in the survival or proliferation of mantle cell lymphoma (MCL) cell lines. P50/p65 complexes were detectable by EMSA assays in 4/5 cell lines. Stable expression of a dominant-negative form of IkBa had no effect on proliferation nor on apoptosis in EBV-negative cell lines.

[Cardiac amyloidosis: a case series of 14 patients, description and prognosis].

Purpose: Cardiac amyloidosis is rare. The objective of this study was to report on a case series of 14 patients with cardiac amyloidosis and to study the prognostic factors.

Methods: Monocentric retrospective study of all adult patients who presented with cardiac amyloidosis, diagnosed at the Georges-Pompidou European hospital in Paris between 2003 and 2011.

[Causes and differential diagnosis of flush].

The flush is a transient and recurrent erythema of the upper region of the body, due to a sudden arterial dilatation. First, physicians should confirm the flush and ascertain the location and timing of skin manifestations. The rapid onset and location of the skin rash to the face and anterior chest are the main characteristics of flush.

Mortality of French participants in the Tour de France (1947-2012).

Aims: In the context of recent concerns regarding performance enhancing techniques and potential negative health effects of high-level physical activity, data on the long-term outcomes and causes of death in elite endurance cyclists are of particular interest.

Methods And Results: Characteristics and vital status of all French participants in the Tour de France were collected for the 1947-2012 period. Causes of death were obtained from 1968.

Iatrogenic Cushing's syndrome induced by posaconazole.

Iatrogenic Cushing's syndrome is an undesirable outcome of glucocorticoids treatment. It can be increased by pharmacologic interactions. Glucocorticoid therapy, given in association with ritonavir, and some azole treatments are causes of iatrogenic Cushing's syndrome.

The combination of arsenic, interferon-alpha, and zidovudine restores an "immunocompetent-like" cytokine expression profile in patients with adult T-cell leukemia lymphoma.

Background: HTLV-I associated adult T-cell leukemia/lymphoma (ATL) carries a dismal prognosis due to chemo-resistance and immuno-compromised micro-environment. The combination of zidovudine and interferon-alpha (IFN) significantly improved survival in ATL. Promising results were reported by adding arsenic trioxide to zidovudine and IFN.

Autologous stem cell transplantation in mantle cell lymphoma: a report from the SFGM-TC.

Autologous stem cell transplantation (ASCT) is considered as an attractive treatment option for young mantle cell lymphoma (MCL) patients. This retrospective SFGM-TC study analyzed the outcome of 500 MCL patients treated with ASCT and investigated parameters that may modify the outcome of patients who proceeded to ASCT upfront (n = 396). For all patients, median age at ASCT was 56 years (range, 26-71).

Therapeutic options for adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is the first human malignancy associated with a retroviral infection and occurs in approximately 5 % of the 15 million to 20 million people infected by human T-cell lymphotropic virus 1. In general, ATL is resistant to chemotherapy, and while awaiting new therapeutics, patients commonly face a detrimental progress of the disease and death. The viral oncoprotein Tax is a key player in the cause of ATL and acts by interfering with DNA repair, cell cycle, apoptosis, and proliferative cellular programs.

Leukocyte telomere length in mastocytosis: correlations with depression and perceived stress.

Background: Mastocytosisis a rare disease associated with chronic symptoms related to mast cell mediator release. Patients with mastocytosis display high level of negative emotionality such as depression and stress sensibility. Brain mast cells are mainly localized in the diencephalon, which is linked to emotion regulatory systems.

Deferasirox and vitamin D improves overall survival in elderly patients with acute myeloid leukemia after demethylating agents failure.

The prognosis of acute myeloid leukemia (AML) in elderly (≥65 years) patients is poor and treatment remains non-consensual especially for those who are not eligible for intensive therapies. Our group has shown that in vitro the iron chelator deferasirox (DFX) synergizes with vitamin D (VD) to promote monocyte differentiation in primary AML cells. Herein, we present results from a retrospective case-control study in which the association of DFX (1-2 g/d) and 25-hydroxycholecalciferol (100,000 IU/week) (DFX/VD) was proposed to patients following demethylating agents failure.

Absence of circulating mast cell precursors in paediatric mastocytosis: could it reflect a different pathophysiology between adults and children with mastocytosis?

Background: Mastocytosis is a heterogeneous disease whose different subtypes also vary in aggressivity. Children typically present with cutaneous mastocytosis. We identified, in our previous work, a peripheral CD34-c-Kit+mast cell precursor by flow cytometry in systemic forms but not in cutaneous forms of adult mastocytosis.

[HSP70, an erythropoiesis regulator that determines the fate of erythroblasts between death and differentiation].

Erythropoiesis is finely regulated by two major cytokines, stem cell factor (SCF) and erythropoietin (Epo). Decrease levels of Epo result in caspase activation and erythroid progenitors apoptosis. However, normal erythroid cell maturation requests caspase activation and cleavage of various caspase substrates, except the erythroid transcription factor GATA-1, that is protected by interaction with the chaperone HSP70 in the nucleus.

[Self-sufficiency, needs, prescription and safety of blood products].

The current issues debate will bring together experts around the themes of self-sufficiency (in its national and European aspects) and of needs in cellular blood products. The point of view of the manufacturer and prescribers of blood products will be confronted.

Ineffective erythropoiesis in β -thalassemia.

In humans, β -thalassemia dyserythropoiesis is characterized by expansion of early erythroid precursors and erythroid progenitors and then ineffective erythropoiesis. This ineffective erythropoiesis is defined as a suboptimal production of mature erythrocytes originating from a proliferating pool of immature erythroblasts. It is characterized by (1) accelerated erythroid differentiation, (2) maturation blockade at the polychromatophilic stage, and (3) death of erythroid precursors.

Disseminated toxoplasmosis in non-allografted patients with hematologic malignancies: report of two cases and literature review.

Toxoplasmosis can be a severe opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), and also among solid organ transplant and allogeneic hematopoietic stem cell transplant (HSCT) patients. Patients with low-grade or chronic hematologic malignancies are treated with increasing immunosuppressive regimens and, therefore, represent an emerging population at risk for opportunistic diseases. We report here two cases of disseminated toxoplasmosis occurring in non-allografted hematologic patients with chronic lymphoproliferations.

Thalidomide in systemic mastocytosis: results from an open-label, multicentre, phase II study.

Mastocytosis can lead to organ failure as well as systemic symptoms that can be disabling, with considerable deterioration in quality of life. Beside symptomatic treatments, interferon-α and purine analogues have been shown to be effective but complete or long-term remission is rarely obtained with these drugs. We conducted a phase II, multicentre, study to investigate thalidomide in severely symptomatic indolent and aggressive systemic mastocytosis.