ALBERT

Description: Background Myelodysplastic syndrome (MDS) is a pre-leukemia disease affecting the erythroid, myeloid and megakaryocytic bone marrow production. MDS patients are classified according to the WHO classification of myeloid neoplasms. During the past 15 years management of MDS patients has been stratified according to the International Prognostic Scoring System (IPSS) risk score. Recently a revised version of IPSS has been introduced (IPSS-R). One quarter of LR-MDS in this new IPSS-R were reclassified as having a higher risk and a substantial subset of high risk-MDS (HR-MDS) were reclassified as lower risk. In LR-MDS a differentiation block is observed in the erythroid lineage. The diagnosis and follow up of cytopenias in particular anemia must be the main objective (1). The soluble transferrin receptor (sTfR) directly reflects the erythropoietic activity in individuals without iron defiency and may appreciate ineffective dysplastic erythropoiesis in LR-MDS. In LR-MDS there is also an inverse relationship between EPO level and the degree of anemia but a wide range of EPO levels is found in patients with similar Hb concentrations. Thus the highest EPO levels are found in patients with erythroid hypoplasia in bone marrow. Aims The combination of several biomarkers: Hb, ferritin, EPO and sTfR may be useful in LR-MDS for diagnosis and follow up. Methods A total of 192 patients with LR-MDS were investigated. Median age of the 192 patients was 71 years (21-92) with 56% males, median survival: 54 months, median follow up: 102 months. The stratification according to the WHO criteria and IPSS risk score was realized. Bone marrows were studied and cytogenetic assessment was realized in the same time. Serum concentrations of ferritin, EPO and sTfR has been analyzed by immuno-assays. Hb level was determined on Beckman Coulter apparatus. The follow up of Hb, ferritin, EPO and sTfR was realized every 2 months in patients with supportive care only until the first specific treatment. A multivariate logistic regression analysis to ascertain the correlations between disease progression and studied biological parameters was realized. Results The logistic regression analysis of our results is significant to define a biological evolutive profile of LR-MDS patients with these biomarkers. The combination of these routine parameters may represent a functional erythropoietic follow up in LR-MDS patients (table 1). This biological tool is an easy method to observe the red cell lineage of LR-MDS patients. This combination informs about the progressive ineffective and dysplatic erythropoiesis in LR-MDS patients. The measurement of ferritin which is a correlated parameter in LR-MDS shows the level of iron overload. A normal or high level without inflammation condition excludes an iron deficiency. The EPO level can give a predictive information about the future efficacy of ESA (endogenous EPO 〈 500 U/l). Conclusion With our results and a correlative logistic regression analysis, we can propose a biological scoring system to appreciate the evolutive anemia of LR-MDS progression in patients. In LR-MDS the management of patients may be based on personalized medicine according a risk assessment with IPSS-R, cytogenetics, mutations and HLA typing (2). But an additional biological and functional predictive scoring system informs about the important independent role of dysplasias particularly anemia in LR-MDS patients before to choose a suitable therapy: transfusions, iron chelation, ESA, TGF-ï¢ pathway inhibitors, G-CSF, immun suppressive treatment, lenalidomide, azacytidine, allogeneic HSCT Table 1. Hb ± EPO ±  sTfRDysplastic erythropoiesis without anemia Hb ±  EPO  sTfRStabilized dysplastic erythropoiesis Hb  EPO  sTfRUnstabilized dysplactic erythropoiesis Hb  EPO  sTfRIneffective dysplastic erythropoiesis EPO 〈 500 U/l : ESA may be efficient〉 500 U/l : ESA will be inefficientFerritin level : iron overload References Giagounidis A Management of low-risk myelodysplastic syndromes Hematology Education, 2015, 9 (1), 219-225 Platzbecker U et al Personalized medicine in myelodysplastic syndromes: wishful thinking or already clinical reality? Hematologica, 2015, 100 (5), 568-571 Disclosures No relevant conflicts of interest to declare.

Description: The potential cardiotoxicity of chemotherapic drugs is well known. For example anthracycline-based regimens are extremely effective for various hematological malignancies. The main disadvantage is cardiotoxicity particularly, in elderly patients who are frequently treated with a consequent dose reduction. The diagnosis and prognosis in patients with suspected heart failure needs a specific monitoring by echocardiography during and after chemotherapy regimens. We tested the interest of NT-proBNP as alternative marker for the detection of left ventricular dysfunction. Brain or B-type natriuretic peptide (BNP) and N-terminal fragment of B-type natriuretic peptide (NT-proBNP) are considered to be valuable biomarkers for the detection of disease state in patients with suspected heart failure. Methods During 1 year, blood samples of 31 patients with hematological malignancies, treated with usual chemotherapy were selected on a routine basis. Patients had the diagnosis of acute leukemia (AL), B-chronic lymphocytic leukemia (B-CLL), multiple myeloma (MM) and non Hodgkin lymphoma (NHL). Venous blood was drawn in the early morning and centrifuged at 2000 g for 15 minutes. The obtained clear plasma fraction was stored at −20°C until the assay. All plasma samples were analyzed for NT-proBNP using an electro chemiluminescence immuno assay (proBNP kit Roche Diagnostics, Mannheim, Germany) on Elecsys 2010 analyser. All assays were performed blind to clinical informations on the patients. Results The mean age of the patients was 72 (range: 36–88). There were 15 men (48 %) and 16 women (52 %). Five patients were smokers (16 %) and 7 (22.6%) had cardiovascular diseases (4 hypertension, 2 heart failure, 1 pace maker). Only 3 patients had a subnormal renal function. There were 6 patients with AL, 6 with B-CLL, 11 with MM and 8 with NHL. The administered medications were divided in 3 cardio-toxicity stages: 10 (32.25 %) patients received stage 3 cardiotoxicity regimens, 10 (32.25 %) stage 2 and 11 (35.5 %) stage 1. Fourteen patients (45 %) died in relation with hematological malignancies and none in relation with heart failure. But treatment regimens have been reduced, discontinued, modified or stopped in 7 patients after heart failure diagnosis with echocardiography. All these patients received stage 2 or 3 cardiotoxicity chemotherapy regimens and 4 had prior cardiovascular diseases. The mean age was 74 (range: 66–82). Only one patient is alive in this subgroup. Considering the age and the heart state of our 31 patients, chemotherapeutic treatments need or not to be adjust. The cardiac risk at diagnosis was assessed by left-ventricular ejection fraction (VEF) measurement. We shows that NT-proBNP brings reliable results to assess that risk, with a positive correlation to the VEF. Figure Figure Conclusion Despite the limitations of this preliminary study the measurement of the NT-proBNP concentration at baseline and during cardiotoxic regimens in patients with hematological malignancies seems to be a promising method to identify patients with an increased risk of cardiovascular adverse effects for it evolves earlier than VEF and is very well correlate to VEF loss and cardiotoxicity.