The Transparency Committee (TC) in France plays a crucial role in the evaluation of post-market authorization (MA) drugs for reimbursement by the social security system. Although its organization has ...evolved since its creation, the principle of its existence has persisted since the establishment of the social security system. The TC, transitioning from the Medicines Agency to the Haute Autorité de santé in 2005, focuses on the medico-scientific evaluation of drugs, influencing decisions on reimbursement eligibility and price negotiations. It assesses the benefit and added medical value of drugs. Comprising experts with no conflicts of interest with pharmaceutical companies, the TC conducts a scientific evaluation of submissions by pharmaceutical laboratories. Recently, it has also been involved in evaluating requests for early access authorization prior to MA.
Bone marrow (BM) failure (BMF) in children and young adults is often suspected to be inherited, but in many cases diagnosis remains uncertain. We studied a cohort of 179 patients (from 173 families) ...with BMF of suspected inherited origin but unresolved diagnosis after medical evaluation and Fanconi anemia exclusion. All patients had cytopenias, and 12.0% presented ≥5% BM blast cells. Median age at genetic evaluation was 11 years; 20.7% of patients were aged ≤2 years and 36.9% were ≥18 years. We analyzed genomic DNA from skin fibroblasts using whole-exome sequencing, and were able to assign a causal or likely causal germ line mutation in 86 patients (48.0%), involving a total of 28 genes. These included genes in familial hematopoietic disorders (GATA2, RUNX1), telomeropathies (TERC, TERT, RTEL1), ribosome disorders (SBDS, DNAJC21, RPL5), and DNA repair deficiency (LIG4). Many patients had an atypical presentation, and the mutated gene was often not clinically suspected. We also found mutations in genes seldom reported in inherited BMF (IBMF), such as SAMD9 and SAMD9L (N = 16 of the 86 patients, 18.6%), MECOM/EVI1 (N = 6, 7.0%), and ERCC6L2 (N = 7, 8.1%), each of which was associated with a distinct natural history; SAMD9 and SAMD9L patients often experienced transient aplasia and monosomy 7, whereas MECOM patients presented early-onset severe aplastic anemia, and ERCC6L2 patients, mild pancytopenia with myelodysplasia. This study broadens the molecular and clinical portrait of IBMF syndromes and sheds light on newly recognized disease entities. Using a high-throughput sequencing screen to implement precision medicine at diagnosis can improve patient management and family counseling.
•Next-generation sequencing broadens the spectrum of germ line mutations in a cohort of patients with likely-inherited BMF.•Salient clinical features and distinct natural histories are consistently found in SAMD9L and SAMD9, MECOM/EVI1, and ERCC6L2 disorders.
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Hematopoietic stem cells are capable of self-renewal and have the outstanding property of giving rise to all blood and immune cells in a stable manner. Autologous and allogeneic therapeutic use of ...these cells has become a standard of care for various malignant and non-malignant hematological diseases. Both procedures are associated with a high level of medicalization, drug prescription, intra-hospital transfer, and ICU use. We sought to put forward ten important tips for the management of critically ill hematopoietic stem cell transplant (HSCT) recipients
Abstract The number of patients living with hematological malignancies (HMs) has increased steadily over time. This is the result of intensive and effective treatments that also increase the ...probability of infiltrative, infectious or toxic life threatening event. Over the last two decades, the number of patients with HMs admitted to the ICU increased and their mortality has dropped sharply. ICU patients with HMs require an extensive diagnostic workup and the optimal use of ICU treatments to identify the reason for ICU admission and the nature of the complication that explains organ dysfunctions. Mortality of ARDS or septic shock is up to 50%, respectively. In this review, the authors share their experience with managing critically ill patients with HMs. They discuss the main aspects of the diagnostic and therapeutic management of critically ill patients with HMs and argue that outcomes have improved over time and that many classic determinants of mortality have become irrelevant.
SEE PDF No specific patient or disease (age, sex, performance status, measurable residual disease level, white blood cell count, neutrophils and lymphocytes count, nervous system infiltration, ...previous allogenous stem cell transplantation, c-reactive protein level) characteristics were significantly associated with LTC occurrence. Life-threatening events occurred in 9% of B-ALL patients treated with blinatumomab in our cohort, necessitating ICU admission in 7% of the cases, which compares favorably with the rate observed after intensive chemotherapy (17.5%) 4 or CAR-T cells (32%) 5. Availability of data and materials The datasets used and/or analyzed in the current study are available from the corresponding author on reasonable request.
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