Somatic genetic alterations predict hematological progression in GATA2 deficiency

Germline GATA2 mutations predispose to myeloid malignancies resulting from the progressive acquisition of additional somatic mutations. Here we describe clinical and biological features of 78 GATA2-deficient patients. Hematopoietic stem and progenitor cell phenotypic characterization revealed an exhaustion of myeloid progenitors. Somatic mutations in STAG2, ASXL1 and SETBP1 genes along with cytogenetic abnormalities (monosomy 7, trisomy 8, der(1;7)) occurred frequently in patients with GATA2 germline mutations. Patients were classified into three hematopoietic spectra based on bone marrow cytomorphology. No somatic additional mutations were detected in patients with normal bone marrow (spectrum 0), whereas clonal hematopoiesis mediated by STAG2 mutations was frequent in those with a hypocellular and/or myelodysplastic bone marrow without excess blasts (spectrum 1). Finally, SETBP1, RAS pathway and RUNX1 mutations were predominantly associated with leukemic transformation stage (spectrum 2), highlighting their implications in the transformation process. Specific somatic alterations, potentially providing distinct selective advantages to affected cells, are therefore associated with the clinical/hematological evolution of GATA2 syndrome. Our study not only suggests that somatic genetic profiling will help clinicians in their management of patients, but will also clarify the mechanism of leukemogenesis in the context of germline GATA2 mutations

Minimal Residual Disease in Acute Myeloid Leukemia: Old and New Concepts

Minimal residual disease (MRD) is of major importance in onco-hematology, particularly in acute myeloid leukemia (AML). MRD measures the amount of leukemia cells remaining in a patient after treatment, and is an essential tool for disease monitoring, relapse prognosis, and guiding treatment decisions. Patients with a negative MRD tend to have superior disease-free and overall survival rates. Considerable effort has been made to standardize MRD practices. A variety of techniques, including flow cytometry and molecular methods, are used to assess MRD, each with distinct strengths and weaknesses. MRD is recognized not only as a predictive biomarker, but also as a prognostic tool and marker of treatment efficacy. Expected advances in MRD assessment encompass molecular techniques such as NGS and digital PCR, as well as optimization strategies such as unsupervised flow cytometry analysis and leukemic stem cell monitoring. At present, there is no perfect method for measuring MRD, and significant advances are expected in the future to fully integrate MRD assessment into the management of AML patients

Atypical cutaneous relapse of multiple myeloma

A 66-year-old patient, diagnosed κ light chains MM with t(11;14), presented before second cycle with bendamustine-dexamethasone. A complete remission was initially obtained with bortezomib-cyclophosphamide-dexamethasone and autologous HSCT. After relapse, he was successively treated with bortezomib-dexamethasone, carfilzomib-dexamethasone, daratumumab-dexamethasone and benda-mustine-dexamethasone

Tracheotomy in ICU

International audienceTracheotomy is widely used in intensive care units, albeit with great disparities between medical teams in terms of frequency and modality. Indications and techniques are, however, associated with variable levels of evidence based on inhomogeneous or even contradictory literature. Our aim was to conduct a systematic analysis of the published data in order to provide guidelines. We present herein recommendations for the use of tracheotomy in adult critically ill patients developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. These guidelines were conducted by a group of experts from the French Intensive Care Society (Societe de reanimation de langue francaise) and the French Society of Anesthesia and Intensive Care Medicine (Societe francaise d'anesthesie reanimation) with the participation of the French Emergency Medicine Association (Societe francaise de medecine d'urgence), the French Society of Otorhinolaryngology. Sixteen experts and two coordinators agreed to consider questions concerning tracheotomy and its practical implementation. Five topics were defined: indications and contraindications for tracheotomy in intensive care, tracheotomy techniques in intensive care, modalities of tracheotomy in intensive care, management of patients undergoing tracheotomy in intensive care, and decannulation in intensive care. The summary made by the experts and the application of GRADE methodology led to the drawing up of 8 formal guidelines, 10 recommendations, and 3 treatment protocols. Among the 8 formal guidelines, 2 have a high level of proof (Grade 1+/-) and 6 a low level of proof (Grade 2+/-). For the 10 recommendations, GRADE methodology was not applicable and instead 10 expert opinions were produced

Accurate classification of plasma cell dyscrasias is achieved by combining artificial intelligence and flow cytometry

International audienceMonoclonal gammopathy of unknown significance (MGUS), smouldering multiple myeloma (SMM), and multiple myeloma (MM) are very common neoplasms. However, it is often difficult to distinguish between these entities. In the present study, we aimed to classify the most powerful markers that could improve diagnosis by multiparametric flow cytometry (MFC). The present study included 348 patients based on two independent cohorts. We first assessed how representative the data were in the discovery cohort (123 MM, 97 MGUS) and then analysed their respective plasma cell (PC) phenotype in order to obtain a set of correlations with a hypersphere visualisation. Cluster of differentiation (CD)27 and CD38 were differentially expressed in MGUS and MM (P = 95% when PC dyscrasias were suspected, without any misclassification between MGUS and SMM. We validated this algorithm in an independent cohort of PC dyscrasias (n = 87 MM, n = 41 MGUS). This artificial intelligence model is freely available online as a diagnostic tool application website for all MFC centers worldwide ()