[Management of myelodysplastic syndromes in 2019: An update]. / Prise en charge des syndromes myélodysplasiques en 2019 : mise au point.

Myelodysplastic syndromes are a heterogeneous group of clonal myeloid disorders characterized by peripheral cytopenias and an increased risk of progression to acute myeloid leukemia. Inflammatory, auto-immune or syndromic symptoms can make the diagnosis difficult. Diagnosis is currently based on bone marrow cytology but cytogenetics and molecular features are currently overpassing their initial prognostic function (allowing early diagnosis and prediction of therapeutic response). The prognostic classification is based on the Revised International Prognostic Scoring System, which also provides guidance for therapeutic management. The treatment of low-risk myelodysplastic syndromes is based on the correction of cytopenias (erythropoiesis stimulating agents, transfusions, lenalidomide, etc.), whereas in high-risk group, the goal is the control of the leukemic clone (hypomethylating agents, allograft of hematopoietic stem cell transplantation). Other molecules are used to manage complications of cytopenias or transfusion (anti-infectious prophylaxis and treatments, martial chelation). New molecules are being studied with some interesting results (luspatercept, venetoclax). This article aims to provide an update on the knowledge that an internist should know for the practical management of myelodysplastic syndromes in 2019.

Improved Fetal Hemoglobin With mTOR Inhibitor-Based Immunosuppression in a Kidney Transplant Recipient With Sickle Cell Disease.

Fetal hemoglobin induction is a key point in the management of sickle cell disease (SCD). We report the case of a kidney transplant recipient with SCD who was treated with everolimus, a mammalian target of rapamycin inhibitor. At 10 months after initiating therapy, the patient's fetal hemoglobin level was dramatically increased (from 4.8% to 15%) and there was excellent tolerance to treatment.

[Cryofibrinogenemia: a single-center study at the University Hospital of Toulouse, France]. / Cryofibrinogénémie : étude monocentrique au CHU de Toulouse.

PURPOSE: Cryofibrinogenemia is an unknown disorder and studies dedicated to it are limited. The aim of our study was to report on the incidence, clinical manifestations and associated diseases in patients with isolated cryofibrinogenemia. METHODS: This is a retrospective single-center study. Patients included in this study had a positive and isolated detection of cryofibrinogen between January 1st, 2011 and December 31st, 2012. Identification was possible through the database of the laboratory of immunology. RESULTS: Two hundred and eighty-one consecutive orders of cryofibrinogenemia were identified. Seventy-three patients had a positive detection of cryofibrinogenemia. Among them, 12 had an isolated cryofibrinogenemia and sixty-one patients (84%) had concomitant cryofibrinogenemia and cryoglobulinemia. The mean age was 59±19years. Seven patients were female (58%). Cutaneous manifestations were present in half case. Peripheral nerve involvement was present in 5 cases (42%) and rheumatic manifestations in 4 patients (33%). A thrombotic event was reported in 7 patients (58%). Renal impairment was present in 7 patients. The median cryofibrinogen concentration was 254±304mg/L. Five patients had a secondary cryofibrinogenemia. The most often prescribed treatment was corticosteroids. CONCLUSION: Cryofibrinogenemia is an unknown disorder. Testing for cryoglobulinemia is more frequent than for cryofibrinogenemia whereas clinical manifestations are similar. Detection of cryofibrinogen is positive in most of the cases, with an important prevalence of thrombotic events in this population. This study confirms the importance of conducting prospective studies on cryofibrinogenemia.

High response rate and improved exercise capacity and quality of life with a new regimen of darbepoetin alfa with or without filgrastim in lower-risk myelodysplastic syndromes: a phase II study by the GFM.

Darbepoetin (DAR), with or without granulocyte colony-stimulating factor (G-CSF), has proved effective in treating anemia in patients with lower-risk myelodysplastic syndrome (MDS), but its effects on quality of life (QoL) and exercise functioning are less well established. In this phase II study (no. NCT00443339), lower-risk MDS patients with anemia and endogenous erythropoietin (EPO) level <500 IU/L received DAR 500 µg once every 2 weeks for 12 weeks, with G-CSF added at week 12 in non-responders. Physical performance was assessed with the 6-min walking test and, for fit patients, maximal oxygen consumption (VO2max). QoL was evaluated using SF-36 and FACT-An tests. In 99 patients, erythroid response rate according to IWG 2006 criteria was 48 and 56 % at 12 and 24 weeks, respectively. Addition of G-CSF rescued 22 % of non-responders. In 48 % of the responders, interval between darbepoetin injections could be increased for maintenance treatment. Serum EPO level was the only independent predictive factor of response at 12 weeks, and its most discriminant cutoff value was 100 IU/L. QoL and VO2max showed improvement over time in responders, compared with non-responders. With a median follow-up of 52 months, median response duration was not reached, and 3-year cumulative incidence of acute myeloid leukemia and overall survival (OS) was 14.5 and 70 %, respectively. Baseline transfusion dependence, International Prognostic Score System (IPSS), and Revised IPSS accurately predicted OS from treatment onset. Tolerance of darbepoetin was good. In conclusion, this regimen of darbepoetin every 2 weeks yielded high response rates and prolonged response duration. Objective improvement in exercise testing and in patient-reported QoL confirms the clinical relevance of anemia correction with erythropoiesis-stimulating agents.