Chelation Therapy In Patients Research Articles

Prevalence of Iron Overload and Chelation Therapy in patients of Thalassemia Major and Knowledge and Attitude of Population towards Iron Chelation Therapy in Sargodha, Pakistan

Background: Whether familial or sporadic, whatever the cause may be, among hereditary hematological disorders, thalassemia accounts for 4.5 out of 10,000 live births worldwide1. Among other complications that these patients have, magnitude of transfusion related iron overload ranges from 9.5%-18%2. Prevalence of post transfusion iron overload in Southeast Asia is much higher than Western world3. Aim: To measure the prevalence of iron overload and chelation therapy in patients of thalassemia major and knowledge and attitude of population towards iron chelation therapy in Sargodha, Pakistan. Methods: This was a cross-sectional study conducted at Rai Hospital, a private-sector hospital and Hilal-e-Ahmar Hospital in Sargodha. Total 390 patients of beta thalassemia major aged 1 month-20 years were included in the study. Data Records of 390 patients of beta thalassemia major, confirmed on hemoglobin electrophoresis admitted in the hospital from June 2021 to June 2022 were included. Data were collected on socio-demographics clinical and laboratory profile. Analysis was done in SPSS Results: The mean age of the participants was 8.79 years, and 51.2 % were males and 48.9 % were females. Iron overload was found in 85.64% % of patients. Highest figure was 18,666ng/ml. Mean serum ferritin level was 3815 ng/ml. 30.2% received regular chelation therapy; 35.3%was on irregular chelation therapy and in 34.3% it was not started yet. Significant factors associated with iron overload and lack of chelation therapy were highly constrained socioeconomic status, repeated and frequent transfusions, lack of knowledge of importance of chelation therapy and unawareness of complications of transfusion. Conclusion: Considering the prevalence and perils of disease itself and treatment related complications government should focus on establishing thalassemia centers nationwide to cater problems faced by these patients where trained doctors and paramedical staff can counsel them regarding disease prognosis and importance of iron chelation therapy in course of disease. Keywords: Prevalence, iron overload, thalassemia major, chelation therapy

Endocrine Complications and the Effect of Compliance with Chelation Therapy in Patients with Beta Thalassemia Major in Eastern Province of Saudi Arabia.

Endocrinopathies and metabolic complications are common in beta thalassemia major patients receiving blood transfusions. Chelation therapy has a role in preventing or delaying such complications. However, patients may face difficulties adhering to chelation therapy for several reasons. To evaluate endocrine complications in beta thalassemia major patients (2-30 years) in the Eastern Province of Saudi Arabia and compare the onset of endocrine complications among compliant and noncompliant patients. Moreover, we assessed the barriers that hinder compliance with chelating therapy. A cross-sectional study was conducted on 89 patients (43 males and 46 females) aged 2 to 30 years attending different hospitals in the Eastern Province of Saudi Arabia. A semi-structured questionnaire was used to collect demographic data and medical histories. The questionnaires were completed by face-to-face interviews with the patients or their caregivers, and the required laboratory data were retrieved from the medical records of patients. The most prevalent abnormality was underweight detected in (40.9%) of patients, followed by subclinical hypothyroidism (37.7%), short stature (35.2%), hypothyroidism in (17.0%) and diabetes mellitus in (13.6%). A significant difference between those who were compliant with iron chelation therapy and those who were not in terms of the prevalence of short stature (P value=0.05) and hypothyroidism (P value=0.05). The percentage of patients who were not compliant with chelation therapy was 21.6% and 9.1% of patients were not taking them at all. Despite the role of chelation therapy in the management of iron overload, the risk of secondary endocrine and metabolic complications remained considerable. Subclinical hypothyroidism and short stature were the most frequent endocrine complications encountered in this study.

Comparative characteristics of humoral immunity indicators and their relationship with chelation therapy in thalassemia

Introduction. Data on the increased susceptibility of patients with thalassemia to infections are of great interest to the study of various aspects of the immune status of patients.Aim. The aim of the study was to study the parameters of the humoral immunity and their relationship with chelation therapy in patients with thalassemia.Materials and methods. This study was carried out at the Republican Specialized Scientific and Practical Medical Center for Hematology from 2015 to 2020. The material of the study was the peripheral venous blood of patients with thalassemia. When determining the immunological status of patients with β-thalassemia, we examined 74 schoolchildren, aged 8–12 years. Statistical processing of clinical material was carried out using the statistical package of application programs STATISTICA 10.0.Results and discussion. The results of the study of the content of serum immunoglobulins in the blood of sick children showed a reduced synthesis of IgA (p < 0.001). At the same time, the level of IgM was significantly increased in patients with β-thalassemia, compared with the control (p < 0.001), which indicates the presence of acute inflammation in the body. Also, the results of our studies showed that there is a certain tendency to increase the level of IgG (11.2 ± 0.41 pg/ml in control versus 16.13 ± 0.58 pg/ml), there was a significant increase in the synthesis of this immunoglobulin (p < 0.001), this allows us to state about the autoimmune process. In the group of children with β-thalassemia, the level of C-reactive protein (CRP) was 4 times higher than the values of the control group (3.8 ± 0.1 ng/mg in the control versus 15.33 ± 0.17 ng/mg, p < 0.001). The level of lactoferrin in sick children was reduced by 4.2 times compared with the data of the control group. There is a dysregulation of acute phase protein factors – C-reactive protein and lactoferrin. β-thalassemia is characterized by a sharp increase in the level of pro-inflammatory cytokines – the level of IL-6 is increased by 2.9 times, and the level of IL-18 – by 8.7 times.Conclusion. The relationship between the indicators of the immune status and indicators of hemosiderosis was revealed, there is a significant difference in all the studied indicators, the use of chelation therapy contributes to positive dynamics.

Clinical view versus guideline adherence in ferritin monitoring and initiating iron chelation therapy in patients with myelodysplastic syndromes.

In patients with myelodysplastic syndromes (MDS) with >20 transfusions and ferritin levels >1000 μg/L, international guidelines recommend iron chelation therapy (ICT). The study's objective was to determine guideline adherence and the intensity of ferritin monitoring in clinical practice. We performed an observational population-based study using the HemoBase Registry, which contains data of all MDS patients diagnosed since 2005 in Friesland, the Netherlands. Clinical information on transfusions, ferritin measurements, ICT, and clinical performance as defined by age ≤ 80 years, Charlson Comorbidity Index <2 and lower-risk MDS was collected from health records. Two hundred and thirty seven of 292 patients (81.1%) received ≥1 transfusion, and 121 (41.4%) received >20 transfusions. In 57 of these 121 patients (47.1%), ferritin measurements were performed at least once. Clinical performance was significantly associated with monitoring ferritin around the 20th transfusion (RR: 2.49, p= .016). Clinical performance was also associated with initiating ICT (RR: 5.99, p< .001). ICT was offered to 22.3% (n= 25) of eligible patients. In this population-based study, ferritin levels were measured in <50% of MDS patients who received >20 transfusions, and clinical performance was significantly associated with measuring ferritin. Our study suggests that in heavily transfused MDS patients, ferritin monitoring is primarily based on patients' clinical performance rather than guideline recommendations.

ATP7B Genotype and Chronic Liver Disease Treatment Outcomes in Wilson Disease: Worse Survival With Loss-of-Function Variants

Background and AimsAlthough a good genotype-phenotype correlation has not been established in Wilson disease (WD), patients with loss-of-function (LOF) ATP7B variants demonstrate different clinical and biochemical characteristics. We aim to describe long-term treatment outcomes in the chronic liver disease (CLD) phenotype and evaluate an association with LOF variants. MethodsThis was a single-center retrospective review of WD patients with at least 1 variant in ATP7B. Demographic, biochemical, genetic, and clinical parameters were obtained. The composite clinical endpoint of liver transplantation or death was used for probands with CLD phenotype on chelators. ResultsOf 117 patients with hepatic WD: 71 had CLD, 27 had fulminant hepatic failure requiring urgent liver transplantation, and 19 were diagnosed through family screening. Median age at diagnosis was 13.1 (interquartile range, 9.7–17.6) years. In total, 91 variants in ATP7B were identified in the study population. At least 1 LOF variant was present in 60 (51.3%) patients. During median follow-up of 10.7 (interquartile range, 6.7–18.9) years, 10 (14.1%) of the probands with CLD reached the composite endpoint. There was a worse transplant-free survival for patients prescribed chelation therapy in patients with at least 1 LOF variant (P = .03). ConclusionsPatients with WD and CLD phenotype on chelators, who have at least 1 LOF variant in ATP7B, have a worse prognosis during long-term follow up. This subgroup of patients requires close monitoring for signs of progressive liver disease. Sequencing of ATP7B may be used in the diagnosis of WD, and in addition, it may provide useful prognostic information for patients with hepatic WD.

Chelation Therapy in Patients with Cardiovascular Disease: A Systematic Review

Chelation Therapy in Patients with Cardiovascular Disease: A Systematic Review

Chelation Therapy in Patients With Cardiovascular Disease: A Systematic Review.

BackgroundEDTA is an intravenous chelating agent with high affinity to divalent cations (lead, cadmium, and calcium) that may be beneficial in the treatment of cardiovascular disease (CVD). Although a large randomized clinical trial showed benefit, smaller studies were inconsistent. We conducted a systematic review of published studies to examine the effect of repeated EDTA on clinical outcomes in adults with CVD.Methods and ResultsWe searched 3 databases (MEDLINE, Embase, and Cochrane) from database inception to October 2021 to identify all studies involving EDTA treatment in patients with CVD. Predetermined outcomes included mortality, disease severity, plasma biomarkers of disease chronicity, and quality of life. Twenty‐four studies (4 randomized clinical trials, 15 prospective before/after studies, and 5 retrospective case series) assessed the use of repeated EDTA chelation treatment in patients with preexistent CVD. Of these, 17 studies (1 randomized clinical trial) found improvement in their respective outcomes following EDTA treatment. The largest improvements were observed in studies with high prevalence of participants with diabetes and/or severe occlusive arterial disease. A meta‐analysis conducted with 4 studies reporting ankle‐brachial index indicated an improvement of 0.08 (95% CI, 0.06–0.09) from baseline.ConclusionsOverall, 17 studies suggested improved outcomes, 5 reported no statistically significant effect of treatment, and 2 reported no qualitative benefit. Repeated EDTA for CVD treatment may provide more benefit to patients with diabetes and severe peripheral arterial disease. Differences across infusion regimens, including dosage, solution components, and number of infusions, limit comparisons across studies. Additional research is necessary to confirm these findings and to evaluate the potential mediating role of metals.RegistrationURL: https://www.crd.york.ac.uk/; Unique identifier: CRD42020166505.

Use of rapid cardiac magnetic resonance imaging to guide chelation therapy in patients with transfusion-dependent thalassaemia in India: UMIMI study.

AimsTo explore the impact of incorporating a faster cardiac magnetic resonance (CMR) imaging protocol in a low–middle-income country (LMIC) and using the result to guide chelation in transfusion-dependent patients.Methods and resultsA prospective UK–India collaborative cohort study was conducted in two cities in India. Two visits 13 months apart included clinical assessment and chelation therapy recommendations based on rapid CMR results. Participants were recruited by the local patient advocate charity, who organized the patient medical camps. The average scanning time was 11.3 ± 2.5 min at the baseline and 9.8 ± 2.4 min (P < 0.001) at follow-up. The baseline visit was attended by 103 patients (mean age 25 years) and 83% attended the second assessment. At baseline, 29% had a cardiac T2* < 20 ms, which represents significant iron loading, and 12% had left ventricular ejection fraction <60%, the accepted lower limit in this population. Only 3% were free of liver iron (T2* ≥ 17 ms). At 13 months, more patients were taking intensified dual chelation therapy (43% vs. 55%, P = 0.002). In those with cardiac siderosis (baseline T2* < 20 ms), there was an improvement in T2*—10.9 ± 5.9 to 13.5 ± 8.7 ms, P = 0.005—and fewer were classified as having clinically important cardiac iron loading (T2* < 20 ms, 24% vs. 16%, P < 0.001). This is the first illustration in an LMIC that incorporating CMR results into patient management plans can improve cardiac iron loading.ConclusionFor thalassaemia patients in an LMIC, a simplified CMR protocol linked to therapeutic recommendation via the patient camp model led to enhanced chelation therapy and a reduction in cardiac iron in 1 year.

Non-compliance to iron chelation therapy in patients with transfusion-dependent thalassaemia

AimTo determine the proportion of non-compliance to iron chelation therapy (ICT) and its associated factors amongst patients with transfusion-dependent thalassaemia (TDT) in Malaysia. MethodsA cross-sectional study was conducted amongst patients with TDT aged 9 years old and above, who were on iron chelation treatment, attending three tertiary hospitals in Kelantan and Terengganu. The socio-demographic, clinical and chelator history of patients were obtained. The compliance of patients to chelators was assessed using the Medication Compliance Questionnaire (MCQ). Social support was assessed using the Medical Outcome Study–Social Support Survey (MOS). Data was analysed using simple and multiple logistic regression. ResultsThe proportion of non-compliance to ICT was 24.7%. Age, activity restriction and latest serum ferritin level of ≥1000 μg/L were significantly associated with non-compliance to ICT. ConclusionThe non-compliance to ICT amongst patients with TDT in Kelantan and Terengganu is 24.7%. Providing motivational interview, enhanced self-empowerment of patients and psychological support are recommended to improve the non-compliance aspect amongst patients on ICT.

Chelation Therapy in Patients with Cardiovascular Disease: A Systematic Review

BACKGROUND AND AIM: Ethylenediaminetetraacetic acid (EDTA) is an intravenous chelating agent with high affinity to divalent cations (e.g. lead, cadmium, calcium) that may be beneficial in the treatment of cardiovascular disease (CVD). While a large randomized clinical trial (RCT) funded by the National Institutes of Health showed benefit, other smaller studies were inconsistent. We performed a systematic review of published studies to examine if EDTA improves clinical outcomes in adults with CVD. METHODS: We conducted a systematic search of 3 databases (MEDLINE, Embase and Cochrane) from database inception to November 5, 2019 to identify all studies involving EDTA chelation treatment in patients with CVD. Predetermined outcomes included mortality, disease severity, plasma biomarkers of disease chronicity, and quality of life. RESULTS:We found 23 studies (4 RCTs and 19 before/after studies) that assessed the use of repeated EDTA chelation treatment in patients with pre-existent CVD. Of these, 16 studies (1 RCT) found improvement in their respective outcomes following EDTA treatment. The largest improvements were observed in studies with high prevalence of participants with diabetes and/or severe occlusive arterial disease, including peripheral artery disease (PAD). CONCLUSIONS:Repeated EDTA for CVD treatment may provide more benefit to patients with diabetes and severe PAD. EDTA excretes metals from the body that are known to induce inflammatory and oxidative processes involved in the progression of diabetes and atherosclerosis. Research is necessary to confirm these findings and to evaluate the potential mediating role of metals. KEYWORDS: Cardiovascular Diseases, Heavy Metals

Exploring the Clinical Utility of Renal Safety Biomarkers during Iron Chelation Therapy in Patients with β-Thalassemia and Other Anemias

Background: Close monitoring of renal function is recommended before and during treatment with the iron chelators deferasirox and deferoxamine (DFO), by assessment of serum creatinine (SCr) and estimated creatinine clearance. To identify patients at increased risk for acute kidney injury while on therapy, efforts are focused on protein biomarkers to predict changes in renal function before SCr increases and to understand the pathophysiology involved. Alpha-1 microglobulin (alpha1M), beta-2 microglobulin (beta2M), retinol-binding protein (RBP), and (urinary) cystatin C increases may reflect proximal tubular dysfunction. Changes in kidney injury molecule-1 (KIM-1), lipocalin-2 (also called NGAL), N-acetyl-beta-glucosaminidase (NAG), clusterin, osteopontin, and tissue inhibitor of metalloproteinase-1 (TIMP-1) may reflect localized pathological processes in the renal nephron. KIM-1 is upregulated dramatically upon epithelial injury and is specific for the proximal tubule. Urinary total protein, microalbumin, and immunoglobulin G (IgG) may reflect either glomerular or tubular injury. The current exploratory analysis assessed 19 renal protein biomarkers as early indicators for an increased risk of acute renal dysfunction in chelated, transfusion-dependent patients with β-thal or other anemias. Objectives were to explore: 1) changes in biomarker profiles over time; 2) correlations between baseline biomarker levels and changes in SCr during treatment; 3) the correlation of changes in biomarker levels with changes in SCr during treatment; 4) correlations between early biomarker changes during treatment with subsequent changes in serum creatinine.Methods: Archived urine samples collected at baseline and every 3-6 months during two deferasirox clinical trials (comparative 1-year 107 study of β-thal patients randomized to deferasirox or DFO; non-comparative 2-year 108 study including β-thal or other anemia [MDS, DBA, rare anemias] patients, excluding SCD) were used. All patients enrolled were aged ≥2 years, received at least 8 blood transfusions/year, and had LIC ≥2 mg Fe/g dw. No patient had baseline SCr >upper limit normal. Patients at risk of acute renal dysfunction were defined as having SCr increased >33% from baseline on ≥2 consecutive visits during the trials. ROC curves were generated by treatment and by underlying disease to determine whether urinary renal markers at baseline (pre-treatment) or change from baseline could predict an increased risk of acute renal dysfunction.Results: 586 β-thal patient samples were assessed from the comparative trial (n=296 deferasirox, n=290 DFO) and 184 from the non-comparative trial (n=85 β-thal; n=99 other non-β-thal anemias [MDS, n=47; DBA, n=30; other rare anemias, n=22]). No significant progressive changes in any renal biomarkers were observed; including acute renal injury (KIM-1, NGAL) and inflammatory (clusterin, osteopontin) biomarkers. Biomarker levels at baseline showed little/no correlation with changes in SCr. Area under the ROC curve (AUC) values were 0.45-0.60, suggesting limited predictive value for urinary renal biomarkers at baseline (pre-treatment) to predict an increased risk of acute renal dysfunction (1.0 = a perfect test, 0.5 = no better than a random test). Weak, though consistent positive correlations were identified between logged fold-change from baseline for biomarkers of renal protein reabsorption and glomerular filtration (alpha1M, beta2M, RBP, microalbumin, total protein, IgG) versus relative change in SCr from baseline over time (r=0.1-0.3) across patient groups. Better associations were identified in non-β-thal patients. Confirmed increase in SCr had the most association with RBP (Fig 1A) and beta2M (Fig 1B) in deferasirox- and DFO-treated patients, respectively. In the non-comparative trial, AUC values were 0.4-0.6 for β-thal patients; most association with NGAL (Fig 1C). In patients with other anemias, nine renal biomarkers had AUCs >0.6; most association with alpha1M (Fig 1D).Conclusions: Without definitive associations with SCr, findings do not support the clinical utility of any of the 19 renal protein biomarkers assessed for monitoring kidney function. The absence of progressive renal biomarker changes at the population level indicates that chelation therapy with deferasirox or DFO did not lead to acute/chronic or progressive renal dysfunction in these studies. [Display omitted] DisclosuresCappellini:Vifor: Honoraria; Celgene: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding, Speakers Bureau; Novartis: Speakers Bureau. Quebe-Fehling:Novartis: Employment. Dieterle:Novartis: Employment. Porter:Bluebird Bio: Consultancy; Agios Pharmaceuticals: Consultancy, Honoraria; Shire: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Celegene: Consultancy.

Effects of omega-3 fatty acids, vitamins, and chelation therapy in patients with heart diseases

Effects of omega-3 fatty acids, vitamins, and chelation therapy in patients with heart diseases

Pathology of Hepatic Iron Overload

Pathology of Hepatic Iron Overload

The serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia: is there a good correlation?

ABSTRACT Introduction Liver iron overload is common in patients with thalassemia. In patients with beta-thalassemia, the correlation between serum ferritin and liver iron concentration is well established. The correlation between serum ferritin levels and liver iron concentrations in patients with alpha-thalassemia remains limited. Methods This is a cross-sectional study in patients with alpha-thalassemia aged ≥ 18 years old at Srinagarind Hospital, Khon Kaen University, Thailand. Liver iron concentration (LIC) was evaluated by the MRI-T2* technique. Linear logistic regression analysis was used to determine the correlation between serum ferritin levels and liver iron concentrations. Results One hundred and thirty-one of the MRI-T2* measurements from 65 patients with alpha-thalassemia were evaluated. Patients with non-deletional alpha-thalassemia had higher LIC compared to patients with deletional alpha-thalassemia. The serum ferritin levels were relatively low at the same levels of LIC in patients with non-deletional alpha-thalassemia compared to deletional alpha-thalassemia. Conclusions The correlation of serum ferritin levels and LIC was modest and different among alpha-thalassemia genotypes. A different serum ferritin threshold is needed to guide iron chelation therapy in patients with alpha-thalassemia. Evaluation of liver iron concentration is necessary for patients with alpha-thalassemia, especially in patients with non-deletional alpha-thalassemia.

Evaluation on curative effects of ethylene diamine tetra-acetic acid chelation therapy in treating with atherosclerotic cardiovascular disease: A protocol for systematic review and meta-analysis.

Background:Ethylene diamine tetra-acetic acid (EDTA) is a chelating agent which attach to metals such as calcium and enables their elimination. In particular, some researchers suggest chelation with EDTA to treat cardiovascular disease with the hypothesis of moderating calcium to decrease atherosclerotic calcification of arteries. However, chelation with EDTA therapeutic effects in atherosclerotic cardiovascular disease is still unclear. Therefore, we propose to undertake a meta-analysis to assess the curative effects of EDTA chelation therapy in patients with atherosclerotic cardiovascular disease.Methods:In the current study, we set to perform a systematic literature search using the electronic databases of 4 most commonly used English databases (EMBASE, MEDLINE, Cochrane Library, and ClinicalTrials.gov trials register), as well as 3 most commonly employed Chinese databases (China Nation Knowledge Infrastructure, Wan Fang, and VIP), from the date of database inception until September 30, 2020 to identify relevant randomized controlled studies of the evaluation on curative effects of EDTA chelation therapy in patients with atherosclerotic cardiovascular disease. In the study, 2 authors worked independently to screen search results, chose studies for inclusion, then they extracted pertinent data to evaluate and study quality based on Cochrane Risk of Bias Tool V.2.0. Additionally, we will address discrepancies by consultation with a third author. We also intend to use pooled risk ratio (RR) and pooled mean difference (MD) or pooled standardized mean difference (SMD) with 95% confidence intervals (CI) to approximate the relative strength of curative effects of EDTA chelation therapy in patients with atherosclerotic cardiovascular disease.Results:The results of the current study will systematically assess curative effects of EDTA chelation therapy in patients with atherosclerotic cardiovascular disease.Conclusion:The study will infer the currently published evidence to evaluate curative effects of EDTA chelation therapy in patients with atherosclerotic cardiovascular disease, which might be beneficial to these patients.Ethics and dissemination:The present study is a systematic review, hence the pooled results are founded upon the published evidence. Therefore, ethical approval is not necessary for the study.Open Science Framework Registration Number:October 20, 2020.osf.io/tvmk8. (https://osf.io/tvmk8/).

Novel dynamic outcome indicators and clinical endpoints in myelodysplastic syndrome; the European LeukemiaNet MDS Registry and MDS-RIGHT project perspective.

Available evidence suggests that in most patients with LR-MDS the risk of death is not related to disease progression but is mainly attributable to non-leukemic death. 2,17 In addition, a proportion of these patients have prolonged survival that precludes the design of clinical trials adopting OS as a primary endpoint. These challenges have resulted in potentially biased assessment of the effectiveness and appropriate use of the available interventions in this patient population. The EUMDS Registry has identified novel meaningful outcome indicators and clinical endpoints, and reliable measures of response to HCI (Figure 4). The results of our analysis indicate that RBCT density is strongly associated with a decreased OS, even at relatively low dose densities. In addition, we observed that an early decrease in platelet count is an independent adverse prognostic indicator in LR-MDS, and combining relative platelet drop and transfusion dependency allows early identification of patients at risk of rapid progression, and may guide early therapeutic interventions, including allogeneic hematopoietic stem cell transplantation or experimental interventions. Taken together, these results indicate that regular RBCT requirement, early platelet count kinetics, and restriction in HRQoL are early independent and meaningful outcome indicators, and reliable measures of effectiveness of therapeutic interventions, evaluated in this set of studies. These findings support the integration of RBCT requirement and HRQoL in the general core outcome sets and in response criteria in patients with LR-MDS, and have important implications for clinical practice and the design of clinical endpoints. Our results strongly support the adoption of freedom from transfusion as a meaningful clinical endpoint in patients with LR-MDS. Anemia is the main determinant of therapeutic intervention in patients with LR-MDS, and ESA are recommended as first-line treatment for patients with symptomatic anemia. 10 The observational studies within the EUMDS Registry showed that the response rate, as well as the capacity of these agents to delay the onset of a regular RBCT need, is most pronounced in RBCT-naive patients. These results identified early initiation of treatment with ESA as a major treatment response indicator, and indicate that ESA should be recommended in LR-MDS patients with symptomatic anemia before starting regular RBCT. After the onset of RBCT dependency, patients with LR-MDS are prone to long-term accumulation of iron. 1,43 The EUMDS Registry studies provided evidence that elevated LPI levels are associated with reduced survival in RBCT dependent patients, whereas iron chelation therapy normalizes LPI levels. These findings suggest that NTBI and LPI may serve as early indicators of iron toxicity and a means to measure the effectiveness of iron chelation therapy in patients with LR-MDS. However, qualified NTBI and LPI are only currently available in specialized laboratories. 44 Large observational cohorts with detailed clinical and laboratory data, like the EUMDS cohort, are the ideal framework in which to identify well defined MDS subtypes that may benefit from novel targeted treatments. An example of such a subtype is MDS with loss of parts of chromosome 5, namely del5q; these patients have a relatively favorable outcome on lenalidomide treatment. In order to identify homogeneous subsets of patients within MDS, preliminary evidence has suggested that recently identified mutations in splicing factors may recognize distinct disease entities within myeloid neoplasms. 45 Splicing modulators are now in pre-clinical testing, and are very likely to lead to the introduction of effective drugs for specific groups of MDS patients. Luspatercept, a specific inhibitor of growth and differentiation factor-11, a member of the transforming growth factor β superfamily, induced substantial improvement of anemia, especially in patients with ring sideroblasts. 46 Characterization of individual cases by new genetic markers (one of the main objectives of the MDS-RIGHT project) will allow refined classification of patients into biological subgroups that are expected to respond differently to therapeutic interventions to guide discontinuation of those interventions that are less effective or less cost-effective. The main question is whether RCT data and retrospective cohort data in selected tertiary care centers are representative of the 'real world' data of the older patients with LR-MDS in the general population. A careful comparison of the 'real world' data and the RCT data will be needed in order to provide a clear answer to these questions. Meanwhile, the current analyses of data collected over 10 years in the EUMDS Registry provides relevant and important information which could help assess prognosis and response to standard interventions in this older patient group.

Annals for Educators - 21 April 2020.

Annals for Educators - 21 April 2020.

PP-108 - Specifications of chelation therapy in patients with thalassemia intermedia and other thalassemia disorders

PP-108 - Specifications of chelation therapy in patients with thalassemia intermedia and other thalassemia disorders

The Clinical Efficacy of Chelation Therapy in Patients with Myelodysplastic Syndrome, Low Risk

The Clinical Efficacy of Chelation Therapy in Patients with Myelodysplastic Syndrome, Low Risk

Impact of treatment with iron chelation therapy in patients with lower-risk myelodysplastic syndromes participating in the European MDS registry.

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.