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Iron overload due to red blood cell (RBC) transfusions is associated with morbidity and mortality in lower-risk myelodysplastic syndrome (MDS) patients. Many studies have suggested improved survival after iron chelation therapy (ICT), but valid data are limited. The aim of this study was to assess the effect of ICT on overall survival and hematologic improvement in lower-risk MDS patients in the European MDS registry. We compared chelated patients with a contemporary, non-chelated control group within the European MDS registry, that met the eligibility criteria for starting iron chelation. A Cox proportional hazards model was used to assess overall survival (OS), treating receipt of chelation as a time-varying variable. Additionally, chelated and non-chelated patients were compared using a propensity-score matched model. Of 2,200 patients, 224 received iron chelation. The hazard ratio and 95% confidence interval for OS for chelated patients, adjusted for age, sex, comorbidity, performance status, cumulative RBC transfusions, Revised-International Prognostic Scoring System (IPSS-R), and presence of ringed sideroblasts was 0.50 (0.34-0.74). The propensity-score analysis, matched for age, sex, country, RBC transfusion intensity, ferritin level, comorbidity, performance status, and IPSS-R, and, in addition, corrected for cumulative RBC transfusions and presence of ringed sideroblasts, demonstrated a significantly improved OS for chelated patients with a hazard ratio of 0.42 (0.27-0.63) compared to non-chelated patients. Up to 39% of chelated patients reached an erythroid response. In conclusion, our results suggest that iron chelation may improve OS and hematopoiesis in transfused lower-risk MDS patients. This trial was registered at clinicaltrials.gov identifier: 00600860., (Copyright© 2020 Ferrata Storti Foundation.)

Prognosis of lower-risk (International Prognostic Scoring System [IPSS] low/intermediate-1) myelodysplastic syndrome (MDS) is heterogeneous and relies on steady-state assessment of cytopenias. We analyzed relative drops in neutrophil and platelet counts during the first 6 months of follow-up of lower-risk MDS patients. We performed a landmark analysis of overall survival (OS) of lower-risk MDS patients prospectively included in the European LeukaemiaNet MDS registry having a visit at 6 ± 1 month from inclusion to assess the prognostic relevance of relative drops in neutrophils and platelets, defined as (count at landmark - count at inclusion)/count at inclusion. Of 2102 patients, 807 were eligible for the stringent 6-month landmark analysis. Median age was 73 years. Revised IPSS was very low, low, and intermediate/higher in 26%, 43%, and 31% of patients, respectively. A relative drop in platelets >25% at landmark predicted shorter OS (5-year OS, 21.9% vs 48.6% with platelet drop ≤25%, P < 10 -4 ), regardless of baseline IPSS-revised or absolute platelet counts. Relative neutrophil drop >25% had no significant impact on OS. We built a classifier based on red blood cell transfusion dependence (RBC-TD) and relative platelet drop >25% at landmark. Patients with none (62%), either (27%), or both criteria (11%) had 5-year OS of 53.3%, 32.7%, and 9.0%, respectively ( P < 10 -4 ). This classifier was validated in an independent cohort of 335 patients. Combining relative platelet drop >25% and RBC-TD at 6 months from diagnosis provides an inexpensive and noninvasive way to predict outcome in lower-risk MDS. This study was registered at www.clinicaltrials.gov as #NCT00600860., (© 2018 by The American Society of Hematology.)

Conventional karyotype is one of the most relevant prognostic factors in MDS. However, about 50% of patients with MDS have a normal karyotype. Usually, 20-25 normal metaphases (nMP) are considered to be optimal to exclude small abnormal clones which might be associated with poor prognosis. This study evaluated the impact of examining a suboptimal number of metaphases in patients recruited to the EUMDS Registry with low and intermediate-1 risk according to IPSS. Only 179/1049 (17%) of patients with a normal karyotype had a suboptimal number of nMP, defined as less than 20 metaphases analyzed. The outcome (overall survival and progression-free survival) of patients with suboptimal nMP was not inferior to those with higher numbers of analyzed MP both in univariate and multivariate analyses. For patients with an abnormal karyotype, 224/649 (35%) had a suboptimal number of MP assessed, but this did not impact on outcome. For patients with a normal karyotype and suboptimal numbers of analyzable metaphases standard evaluation might be acceptable for general practice, but we recommend additional FISH-analyses or molecular techniques, especially in candidates for intensive interventions., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Myelodysplastic syndrome Working Group of the Croatian Cooperative Group for Hematologic Diseases (CROHEM), Referral center of the Ministry of Health of the Republic of Croatia for diagnostics and treatment of MDS, as well as the Croatian Society for Haematology of the Croatian Medical Association have made Croatian guidelines for diagnosis and treatment of myelodysplastic syndrome (MDS). MDS is a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, dysplasia, cytopenia and risk of transformation to acute myeloid leukemia (AML). Diagnosis is based on morphological characteristics of hematopoietic cells supplemented with the cytogenetic analysis and bone marrow flow cytometry. Due to great differences in the natural course of the disease, i.e. time to progression to AML and the expected time of survival several scoring systems have been developed to determine the disease risk. The treatment of patients with MDS is based on the risk factors of the disease as well as the individual risk of treatment.