Revue Du Praticien最新文献

THERAPEUTIC APPROACHES IN SICKLE CELL DISEASE. Sickle cell disease, the most common genetic disease in France, is still burdened with morbidity and early mortality before the age of 50. When the first-line treatment, hydroxyurea, is insufficient or in the case of organic damage(s) (in particular cerebral vasculopathy), a therapeutic intensification must be considered. New molecules are now available, such as voxelotor and crizanlizumab, but only hematopoietic stem cell (HSC) transplantation can cure the disease. Allogeneic HSC transplantation during childhood with a sibling donor is the reference but it is now possible to perform this procedure in adults with a reduced pre-transplant conditioning. Gene therapy, which consists of an autograft of genetically modified HSCs, has obtained promising results but has not yet demonstrated a complete cure of the disease (protocols underway). The toxicity of myeloablative conditioning (used in pediatrics or for gene therapy), particularly the sterility induced, and the risk of graft-versushost disease (for allogeneic transplantation) are limiting factors of these treatments.

EPIDEMIOLOGY OF SICKLE CELL DISEASE IN FRANCE AND IN THE WORLD. In a few decades, sickle cell disease has become the leading rare disease in France, with nearly 30,000 patients. It is the country in Europe where the most patients live. For historical reasons of immigration, half of these French patients live in the Paris area. The number of births of affected children increases every year, which explains the recurrent and increasing hospitalizations for vaso-occlusive crises, impacting the care system. Sub-Saharan African countries, along with India, are the countries most affected by the disease with an incidence of up to 1% of births. While infant mortality has become rare in industrialized countries, it is major in Africa where more than half of the children will not reach the age of 10.

MANAGEMENT OF ACUTE COMPLICATIONS OF SICKLE CELL DISEASE. Acute complications are the most frequent causes of hospitalization and morbidity in patients with sickle cell disease. Vaso-occlusive crisis are responsible of more than 90% of hospitalization, but numerous acute complications can affect multiples organ or function, that may be life-threatening. Thus, a single reason for hospitalization may include many complications such as worsening of an anemia, vascular disease (stroke, thrombosis, priapism), acute chest syndrome, liver or spleen sequestration. Evaluation of acute complications includes the understanding of chronic complications, particularities related to patient's age, the search for a triggering factor and a differential diagnosis. Analgesia and venous access difficulties, post transfusion immunization, medical history of the patient can make the management of acute complication particularly complex.

THERAPEUTIC ADVANCES IN HER2+ BREAST CANCER. 58,000 new cases of breast cancer occured in France in 2018, of which 15-20% are HER2-positive. HER2-targeted therapies deeply modified the management of these tumors, first by the introduction of monoclonal antibodies such as trastuzumab and pertuzumab and tyrosine kinase inhibitors such as tucatinib, and more recently by antibody drug conjugates (ADC), with trastuzumab-deruxtecan in the forefront. In the localized stage, neoadjuvant chemotherapy associated with trastuzumab is now the standard strategy, allowing the adjuvant strategy to be adapted to the therapeutic response, with the use of another ADC, T-DM1, in the absence of pathological complete response. These various therapeutic advances have led to a significant improvement in the prognosis of HER2-positive breast cancer, whether at the metastatic or localized stage.