Baseline Serum Ferritin Levels Research Articles

Pancreatic iron in pediatric transfusion-dependent beta-thalassemia patients: A longitudinal MRI study.

In pediatric transfusion-dependent thalassemia (TDT) patients, we evaluated the prevalence, pattern, and clinical associations of pancreatic siderosis and the changes in pancreatic iron levels and their association with baseline and changes in total body iron balance. We considered 86 pediatric TDT patients consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. Iron overload (IO) was quantified by R2* magnetic resonance imaging (MRI). Sixty-three (73%) patients had pancreatic IO (R2*>38Hz). Global pancreas R2* values were significantly correlated with mean serum ferritin levels, MRI liver iron concentration (LIC) values, and global heart R2* values. Global pancreas R2* values were significantly higher in patients with altered versus normal glucose metabolism. Thirty-one patients also performed the follow-up MRI at 18±3months. Higher pancreatic R2* values were detected at the follow-up, but the difference versus the baseline MRI was not significant. The 20% of patients with baseline pancreatic IO showed no pancreatic IO at the follow-up. The 46% of patients without baseline pancreatic IO developed pancreatic siderosis. The changes in global pancreas R2* between the two MRIs were not correlated with baseline serum ferritin levels, baseline, final, and changes in MRI LIC values, or baseline pancreatic iron levels. In children with TDT, pancreatic siderosis is a frequent finding associated with hepatic siderosis and represents a risk factor for myocardial siderosis and alterations of glucose metabolism. Iron removal from the pancreas is exceptionally challenging and independent from hepatic iron status.

Myelodysplastic Syndromes and Myelodysplastic Syndromes/Myeloproliferative Neoplasms: A Real-World Experience From a Developing Country.

Myelodysplastic syndromes (MDS) include a heterogeneous group of clonal bone marrow disorders characterized by ineffective hematopoiesis. They manifest as dysplasia in bone marrow hemopoietic elements associated with peripheral cytopenias with variable risk of AML transformation. We analyzed retrospectively registry data collected prospectively from patients with primary MDS and patients with MDS/myeloproliferative neoplasm (MPN) in the Jordan University Hospital between January 2007 and September 2021. The registry captured epidemiologic information such as date of diagnosis, age, gender, date of AML transformation, cytogenetics, MDS subtype, risk group according to Revised International Prognostic Scoring System, and survival. The registry also captured baseline ferritin, B12, and lactate dehydrogenase levels. A total of 112 patients with MDS and MDS/MPN were included in the registry. Median age at diagnosis was 59 years. The male-to-female ratio was about 1.2. In a multivariate cox regression model, baseline serum ferritin significantly affected survival as patients with levels exceeding 1,000 μg/L had a risk of death three times higher compared with those with <1,000 μg/L levels (P < .05). To our knowledge, our study is the first comprehensive study examining the epidemiology and prognostic factors in patients with MDS and patients with MDS/MPN in Jordan. Our results show that MDS and MDS/MPN epidemiology in Jordan is different compared with Western countries. Our results also show that baseline serum ferritin levels can be used as a prognostic marker for patients with MDS.

Bone Marrow Iron Stores Are Not Associated with Increased Risk for Invasive Fungal Infections in Patients with Newly Diagnosed Acute Leukemia or Myelodysplastic Syndrome in Transformation: Is There a Relationship?

Iron plays an important role in the pathogenesis of infections, including invasive fungal infections (IFIs). Studies suggested that iron overload might represent an additional risk factor for IFIs among patients with hematological malignancies. We conducted a prospective, multi-center study amongst adult patients with newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in transformation to determine whether baseline iron overload as measured using the bone marrow iron store (BMIS) score is an independent risk factor for the development of IFIs. We also measured baseline serum iron and ferritin levels. A total of 98 patients were enrolled (76 with AML) and were followed for 12 months. Twenty-two patients developed IFI during the follow-up period (invasive aspergillosis n = 16, candidemia n = 5, mucormycosis n = 1). A baseline BMIS score ≥ 3 indicated that iron overload was relatively common (38/98 patients, 38%), and its frequency was comparable between patients with no IFIs (31/76, 40.7%) and in those with IFIs (8/22, 36.4%). Univariate analysis showed that only the presence of AML was associated with increased risk for IFIs [OR (95% CI) 7.40 (1.05-325.42)]. Both univariate and multivariate analyses showed that an increased BMIS score (≥3) at baseline was not an independent risk factor for IFIs. Similarly, there was no difference in serum iron and ferritin between the two groups that had similar demographic characteristics. Indices of iron overload were not independent risk factors for IFIs in our cohort of Greek patients with newly diagnosed AML/MDS in transformation.

Persistent Increase in Serum Ferritin Levels despite Converting to Permanent Vascular Access in Pediatric Hemodialysis Patients: Pediatric Nephrology Research Consortium Study.

Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL (p = < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year (p = 0.004). The serum ferritin levels did not show a statistically significant linear association with respective serum hematocrit values. In a multiple linear regression model, there were three predictors of serum ferritin during the first year of follow-up: steroid-resistant nephrotic syndrome as primary etiology (p = 0.035), being from a center that enrolled >10 cases (p = 0.049) and baseline serum ferritin level (p = 0.017). Increasing serum ferritin after conversion to PVA is concerning. This increase is not associated with serum hematocrit trends. Future studies should investigate the correlation of serum transferrin saturation and ferritin levels in pediatric HD patients.

Effect of Luspatercept on Red Blood Cell (RBC) Transfusion Burden, Iron Chelation Therapy (ICT), and Iron Overload in Adults with Transfusion-Dependent β-Thalassemia (TDT) from the BELIEVE Trial: A Long-Term Analysis

Effect of Luspatercept on Red Blood Cell (RBC) Transfusion Burden, Iron Chelation Therapy (ICT), and Iron Overload in Adults with Transfusion-Dependent β-Thalassemia (TDT) from the BELIEVE Trial: A Long-Term Analysis

Characterization of Patients with Lower-Risk Myelodysplastic Syndromes Experiencing Long-Term Responses with Luspatercept in the MEDALIST Study

Introduction: Patients with lower-risk myelodysplastic syndromes (LR-MDS) receiving luspatercept in the phase 3 MEDALIST trial previously reported durable episodes of red blood cell (RBC) transfusion independence (RBC-TI) lasting ≥ 8 weeks, with a median cumulative duration of approximately 20 months (Fenaux P, et al. J Clin Oncol 2022;40[16_suppl]:7056). The baseline characteristics of patients who receive long-term luspatercept treatment, as well as the benefits of long-term treatment, warrant further investigation. Here, we report the effect of longer duration of treatment on response, and the baseline characteristics of patients with longer durations of treatment, in patients with LR-MDS receiving luspatercept in the MEDALIST long-term follow-up study. Methods: Eligible patients were ≥ 18 years of age, had LR-MDS requiring RBC transfusions, and were ineligible for, intolerant to, or refractory to erythropoiesis-stimulating agents (ESAs). Patients receiving luspatercept were stratified by duration of treatment, as follows: 0-24, > 24 to 48, > 48 to 144, and > 144 weeks. Efficacy outcomes included: RBC-TI ≥ 8 or 16 weeks; modified hematologic improvement-erythroid (mHI-E) response, based on the International Working Group 2006 definition, over any consecutive 56-day period; and time to acute myeloid leukemia (AML)/high-risk (HR) MDS progression from diagnosis. Results: As of January 15, 2021, of 153 patients randomized to luspatercept, 45 (29.4%), 26 (17.0%), 45 (29.4%), and 37 (24.2%) patients remained on treatment during weeks 0-24, > 24 to 48, > 48 to 144, and > 144, respectively. Baseline characteristics stratified by duration of treatment are shown in the Table. Patients treated for > 48 weeks were younger; had lower baseline transfusion burden, serum ferritin (SF), and erythropoietin (EPO) levels; were more likely to have mutated SF3B1; and less likely to have received ESAs in the 6 months prior to study. Patients treated for ≤ 24 weeks had a longer time since MDS diagnosis (Table 1). The majority of patients received the maximum luspatercept dose level regardless of duration of treatment, with 53.3%, 69.2%, 80.0%, and 73.0% of patients receiving 1.75 mg/kg luspatercept during weeks 0-24, > 24 to 48, > 48 to 144, and > 144, respectively. Median (range) time to first dose increase was generally higher with longer duration of treatment (43 [40-106] vs 91 [41-1023] days at 0-24 and > 144 weeks, respectively). Higher rates of RBC-TI ≥ 8 weeks, RBC-TI ≥ 16 weeks, and mHI-E ≥ 8 weeks were associated with longer durations of treatment (Table 2). Median (range) cumulative duration of RBC-TI ≥ 8 weeks was greater with longer duration of treatment: 66.0 (57-166), 88.5 (62-229), 373.0 (59-936), and 1227.5 (59, 1767) days for patients with a duration of treatment of 0-24, > 24 to 48, > 48 to 144, and > 144 weeks, respectively. Progression to HR-MDS/AML occurred in 3 (6.7%), 2 (7.7%), 7 (15.6%), and 1 (2.7%) patient with a duration of treatment of 0-24, > 24 to 48, > 48 to 144, and > 144 weeks, respectively. The median (range) time from original MDS diagnosis to HR-MDS/AML progression was 66.2 (57.2-223.6), 41.9 (18.8-64.9), 49.0 (33.1-97.6), and 56.7 (56.7-56.7) months for patients with a duration of treatment of 0-24, > 24 to 48, > 48 to 144, and > 144 weeks, respectively. Conclusions: Patients continuing treatment for > 48 weeks were younger and had lower baseline transfusion burden, SF, and EPO levels. Higher rates of RBC-TI and mHI-E response led to longer durations of treatment, and patients with longer durations of treatment were more likely to receive the maximum luspatercept dose level. There were no safety signals in terms of progression to AML/HR-MDS occurring according to the expected prognostic risk profile for these patients. These findings illustrate that patients with LR-MDS receiving long-term luspatercept treatment continue to experience durable responses. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Serum Ferritin Increased the Predictive Value of the International Staging System/Revised International Staging System for Overall Survival

Background Multiple myeloma (MM) is a terminally differentiated plasma cell hematological malignancy. MM remained an incurable disease, accounting for 20% of deaths of hematological malignancies, despite continuous improvements in its treatment. The revised international staging system (RISS) is commonly used in patients with de novo MM, but it has limitations in predicting prognosis. Hence, better prognostic biomarkers and more optimized staging are yet to be explored. Methods This retrospective study reviewed 357 patients with MM at our institution from May 2013 to May 2018 and included a total of 302 patients. Differences in serum ferritin levels between patients with relapse/non-relapse and survival/death were assessed. Multivariate-adjusted Cox regression and K-M curve were conducted to analyze the effect of different serum ferritin levels on progression-free survival (PFS) and overall survival (OS) in 7 years. Further, the receiver operating characteristic (ROC) curve analysis was used to evaluate the role of serum ferritin level in increasing the international staging system (ISS) and RISS in prognosis prediction. Multivariate linear regression and binomial logistic regression assessed the association of serum ferritin level with optimal induction therapy response. Results The serum ferritin level of patients with MM with recurrence was significantly higher than that of patients without recurrence (P < 0.0001), and the serum ferritin level of patients with all-cause death was significantly higher than that of patients who were still alive during the 7-year follow-up period (P < 0.0001). Smooth curve fitting analysis showed that serum ferritin levels were associated with relapse and death occurrences. The K-M curve analysis indicated that MM patients with high ferritin levels (≥577.47 ng/ml) had shorter PFS (P < 0.0056) and OS (P = 0.0014) than those with ferritin levels of <577.47 ng/ml. Multivariate Cox regression analysis adjusted for potential variables showed that MM patients with high serum ferritin had poor PFS (hazard ratio [HR] = 2.07, 95% confidence interval [CI]: 1.33-3.23, P = 0.0012) and OS (HR = 1.84, 95%CI: 1.08-3.16, P = 0.0258), with independent correlation. The prediction model of ROC analysis based on Cox regression showed that ferritin had a predictive value for PFS (ORferritin = 2.158, Pferritin = 0.0219) and OS (ORferritin = 2.2480, Pferritin = 0.0196). Additionally, the ROC curve showed that serum ferritin could increase the predictive value of ISS and RISS for OS. Multivariate regression analysis showed that serum ferritin levels had no significant independently effect on the optimal response within induction therapy. Conclusion This retrospective study showed that baseline serum ferritin levels were associated with prognosis in patients with MM, and patients with higher serum ferritin have poorer PFS and OS. Serum ferritin could increase the prediction value of ISS and RISS for OS.

A Systematic Review and Indirect Treatment Comparison of Ferric Carboxymaltose Versus Iron Isomaltoside in Correcting Iron Deficiency Anemia

Background: Iron deficiency anemia (IDA) is a global public health concern. It is estimated 1.24 billion people with IDA and responsible for about 800,000 deaths per year. Intravenous iron therapy is one of the treatment options and in recent years has been promoted for first-line use in correcting IDA. Currently in the literature, there is a lack of direct evidence of comparative effectiveness between ferric carboxymaltose (FCM) and iron isomaltoside (IIM) in correcting IDA. Available indirect evidence is far from conclusive. With more evidence emerging from the literature, the aim of the current study was to conduct an indirect treatment comparison (ITC) of FCM versus IIM in correcting IDA. Method: To address potential heterogeneity, two separate ITC analyses were proposed: one via iron sucrose (IS) and the other via oral iron (OI) and focused on non-chronic-kidney-disease (non-CKD) patients. A systematic literature review, searching PubMed, EMBASE, and Cochrane Library, was conducted to identify relevant randomized controlled trials (RCTs). The data cut-off date was 2022.03.31. The risk of bias for each involved study was assessed based on the Cochrane review criteria. Bucher's ITC method and random-effects model for meta-analysis were applied to compare outcomes. The efficacy outcomes included the response rate, mostly defined as 2 g/dL increase from baseline or hemoglobin (Hb) level normalized, and hemoglobin level change from baseline. The safety outcome was adverse drug reactions (DARs) and drug-related serious adverse events (SAEs). When feasible, subgroup analyses by underlying disease were also conducted. Results: For ITC via IS, 8 RCTs (7 FCM vs IS and 1 IIM vs IS) were included. Most of the studies presented with the low risk of bias. The total number of patients in FCM and IIM RCTs were 1471 and 1512, respectively. The distribution of baseline characteristics between two groups were: the proportion of female (84.8 vs 89.2%), age (35.7 vs 44.0), baseline Hb level (8.7 vs 9.2 g/dL) and serum ferritin level (10.3 vs 13.6 ug/mL) . The ITC result indicated that FCM had a statistically significant better response rate with a risk ratio (RR) of 1.34 (95% CI: 1.03 - 1.75), compared to IIM. FCM also resulted in a significantly larger increase from baseline Hb level in comparison to IIM, with a mean difference of +0.87 g/dL (95% CI: 0.40 - 1.34). For safety as measured by DARs, FCM showed no significant difference with IIM (RR of 0.80, 95% CI: 0.40 - 1.57). Due to a high number of zero event reported in the studies and different SAE definitions, indirect comparison of SAE was not conducted. For ITC via OI, 17 RCTs (15 FCM vs OI and 2 IIM vs OI) were included. The total number of patients in FCM and IIM RCTs were 3428 and 677, respectively. Between the two groups, the average age (38.1 vs 45.5 years), proportion of female (88.0 vs 65.9 %) and baseline Hb level (9.8 vs 9.9 g/dL) were similar. In the IIM group, half of patients were cancer patients with chemotherapy. The results of the ITC via OI were similar to those via IS. FCM had a non-significant better response rate (RR 1.18, 95% CI: 0.96 - 1.45) and a statistically significant larger increase from baseline Hb level (+0.81 g/dL, 95% CI: 0.37 - 1.25) in comparison to IIM. For safety, there was no significant difference between the two (RR of 1.23, 0.27 - 5.57). Subgroup analysis was conducted in IBD patients (3 FCM and 1 IIM RCT, 486 vs. 327 patients). The result also indicated that FCM had a significantly larger increase from baseline hemoglobin (+0.99 g/dL, 0.86 - 1.13) in comparison to IIM. Conclusion: Based on the current evidence, both indirect treatment comparison analyses indicated that in non-chronic-kidney-disease patients ferric carboxymaltose has better efficacy outcomes than iron isomaltoside and no difference in terms of adverse drug reactions. Future head-to-head trials might be needed to confirm the current findings.

Effects of Ker-050 on Iron Metabolism: Exploratory Analyses from an Ongoing Phase 2 Study in Patients with Myelodysplastic Syndromes

Background: Iron overload (IO) is an important clinical consequence of transfusion-dependent myelodysplastic syndromes (MDS). For patients with high transfusion burden (HTB), limited treatment options are available to effectively treat anemia and reduce transfusion dependence. Transfusion dependence is an independent predictor of poor prognosis in MDS. It is associated with IO and elevated ferritin, a marker of intracellular iron storage that also predicts poor prognosis in MDS. When adjusting for transfusion burden, each 500 µg/L increase in ferritin above 1000 µg/L is associated with a 30% greater risk of death (Malcovati et al. 2006). IO also disrupts osteoprogenitors and erythroid precursors within the osteohematopoietic niche, leading to abnormal bone turnover and ineffective erythropoiesis (Bulycheva 2015). While iron chelators have shown some efficacy in managing IO, they introduce toxicities and have little effect on transfusion burden. Unmet need remains for treatments that effectively address anemia, IO, and reduce transfusion dependence in patients with MDS, especially those with HTB. KER-050 is designed to alter signaling of TGF-β superfamily ligands, restoring balance to the osteohematopoietic niche, and promoting differentiation of erythroid and megakaryocytic precursors. It is a modified activin receptor type IIA ligand trap that inhibits TGF-β superfamily ligands, including activins A and B and growth and differentiation factors (GDFs) 8 and 11. To date, clinical data indicate that KER-050 induces sustained increases in reticulocytes and hemoglobin. Preliminary findings also show potential for KER-050 to induce erythroid response and reduce transfusion burden in patients with MDS, including those with HTB (Tan et al., 2022). KER-050 may also impact iron metabolism and this presentation explores the effects of KER-050 on indices of IO. Methods: This Phase 2 study is evaluating KER-050 in participants with very low- to intermediate-risk MDS. Data presented are from Part 1 Dose Escalation which included 16 weeks of KER-050 treatment across 5 cohorts (0.75 to 5 mg/kg). Iron chelator therapy was permitted at the discretion of the investigator provided patients had been on a stable dose for 8 weeks prior to C1D1. Markers of IO and hematopoiesis were assessed as exploratory endpoints over the 16-week treatment period. Analyses presented evaluate the effect of KER-050 on these markers. Baseline markers of bone turnover were also assessed. Results: A total of 31 patients were enrolled in Part 1 Dose Escalation; 26 were transfusion dependent, 18 with HTB (≥ 4 RBC units in 8 weeks prior to day 1). Seven HTB patients (38.9%) received iron chelator therapy. Baseline differences were noted in measures of iron status, erythropoiesis and bone turnover for non-transfused (NT), low transfusion burden (LTB), and HTB patients (Table 1). HTB patients had the highest baseline serum iron and ferritin levels. Preliminary findings indicate that KER-050 treatment was associated with decreases in serum ferritin for patients both with and without iron chelator therapy. Patients achieving transfusion independence (TI) experienced a 39.5% reduction (mean change: -619.4 ng/ml, range: -2118.4 to +243 ng/mL) in serum ferritin at Week 12 that was generally sustained at Week 16 and 20 (Figure 1). Similarly, over the same time period, serum iron and transferrin saturation (TSAT) decreased by 4.03 µmol/L (8.38%) and 5.3%, respectively, in patients achieving TI. Soluble transferrin receptor (sTfR) increased by 32.2% and remained elevated at subsequent visits. Summary: Preliminary data from the 16-week Dose Escalation in this ongoing phase 2 study reveal differences in baseline iron biomarkers indicative of increasing iron overload with increasing transfusion burden. While nearly half of HTB patients received iron chelator therapy, this group had markedly elevated ferritin compared to NT and LTB patients at baseline. KER-050 treatment was associated with reductions in serum ferritin, irrespective of the use of iron chelation. Patients achieving TI experienced decreases in ferritin, iron and TSAT concurrent with increases in sTfR that were generally maintained through follow-up. The data suggest that, in addition to improving hematopoiesis and transfusion burden in MDS patients, KER-050 may reduce iron overload, a serious clinical complication impacting the survival of these patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Effect of nonsurgical periodontal therapy and smoking status on hematological variables related to anemia of chronic disease in chronic periodontitis patient: a case-control study.

Background Chronic infectious, inflammatory, or neoplastic disorders are associated with anemia of chronic disease. Chronic inflammatory diseases such as periodontitis may contribute to masked anemia, especially in smokers. This study was aimed at verifying and comparing the efficacy of nonsurgical periodontal therapy (NSPT) for improving anemia among chronic periodontitis patients with and without the habit of smoking.Methods Thirty systemically healthy individuals with chronic periodontitis were divided into two groups of 15 each, smokers (group A) and nonsmokers (group B). The groups were compared based on hematological parameters such as serum erythropoietin (SE) and serum ferritin (SF) levels at baseline and 3 months after NSPT for anemia evaluation.Results The baseline SE levels in groups A and B were 11.84 and 15.19 mIU/mL (p=0.031), respectively; the corresponding levels at 3 months after NSPT were 13.00 and 17.74 mIU/mL (p=0.022). The baseline SF levels in groups A and B were 95.49 and 44.86 ng/mL (p=0.018), respectively; the corresponding levels at 3 months after NSPT were 77.06 and 39.05 ng/mL (p=0.009). Group B showed a significant increase and decrease in the SE and SF levels, respectively, at 3 months after NSPT (p=0.035 and p=0.039, respectively), whereas group A showed insignificant changes (p=0.253 and p=0.618, respectively).ConclusionNSPT led to an improvement in anemia among chronic periodontitis patients. However, the improvement is less in smokers compared to that in nonsmokers. Furthermore, SF and SE levels might serve as effective biomarkers for assessing anemia in smokers and nonsmokers with chronic periodontitis.

A comparative study of efficacy, safety and compliance of intravenous ferric carboxymaltose versus iron sucrose in the treatment of iron deficiency anaemia of pregnancy

Iron deficiency is the most common cause of anaemia worldwide and is associated with significant maternal and fetal morbidity. Current options for treatment include oral iron supplementation which can be ineffective and poorly tolerated, intravenous iron which can be used in patients who are intolerant to or unresponsive to oral iron and red blood cell transfusions which carry an inherent risk because of which it should be avoided. Intravenous iron therapy may reduce the requirement for allogenic blood transfusion. Ferric carboxymaltose is a new intravenous iron formulation promising to be more effective and as safe as iron sucrose. It may even have a better compliance as it offers the administration of a much higher iron dosage at a time.The study was designed to compare the efficacy and safety of IV ferric carboxymaltose versus iron sucrose in the treatment of iron deficiency anaemia of pregnant women with moderate anaemia in the second and third trimester.A hospital based randomized prospective study was done from July 2013 to June 2015 in the department of Obstetrics and Gynaecology, A.J. Institute of Medical Sciences, Mangalore. Baseline haemoglobin, peripheral smear and serum ferritin levels were measured to diagnose iron deficiency anaemia. 60 pregnant women who met the inclusion criteria and who formed the study subjects were randomly allocated into two groups comprising of 30 in Group C (Received ferric carboxymaltose) and 30 in Group S (Received iron sucrose). Outcome was assessed by measuring haemoglobin 3 weeks after treatment and a comparison of the safety and efficacy between the two groups was made. In the present study the commonest age group was 21 to 30 years: 80% in group C and 73.3% in group S and mean age of the study population in group C and S was comparable (25.2±3.54 vs 24.8±4.58 years). The socio demographic characteristics, obstetric history, vitals and pretreatment haemoglobin were comparable in both the groups (p&amp;#62;0.050). The post treatment haemoglobin levels in 63.3% of the women in group C compared to 46.7% in group S were found to be 11 or more and mean post treatment haemoglobin levels were comparable in group C and group S (11.016±0.789 vs 10.73±0.821 gm%; p=0.174). In the present study, post treatment mean increase in haemoglobin levels was noted between 2.0 to 2.5 gm% in 43.3% of the women in group C compared to 50.0% in group S. Ferric carboxymaltose administration in pregnant women in the second and third trimesters is well tolerated and is not associated with any clinical safety concerns. Both ferric carboxymaltose and iron sucrose have a comparable safety profile even when ferric carboxymaltose was administered in a much higher dosage compared to iron sucrose. Ferric carboxymaltose should be considered as the drug of choice, if i.v. iron treatment becomes necessary in the second or third trimester of pregnancy.

Prospective Changes of Pancreatic Iron in Thalassemia Major

Introduction. Pancreatic iron deposition is a common finding in thalassemia major, being detected in more than one third of patients undergoing their first T2* Magnetic Resonance Imaging scan (MRI) for this purpose. However, no longitudinal studies on pancreatic iron are available in literature.Aim: The aim of this multicenter study was to evaluate the changes in pancreatic iron overload in TM patients enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) Network who performed a baseline and a follow-up (FU) MRI scan at 18 months.Methods. We considered 416 TM patients (37.77±10.46 years; 220 females) consecutively enrolled. Iron overload was quantified by the T2* technique. T2* measurements were performed over pancreatic head, body and tail and global value was the mean.Results. Pancreatic iron overload (global pancreas T2*<26 ms) was detected in 367 (88.2%) patients. Of them, only 14 (3.8%) improved at the FU. Out of the 49 (11.8%) patients without baseline pancreatic iron overload, 15 (30.6%) showed pancreatic iron overload at the FU MRI.A significant inverse association was detected between % change in global pancreas T2*and baseline global pancreas T2* values (R=-0.369; P<0.0001). Patients with baseline pancreatic iron overload showed significantly higher % changes in global pancreas T2* values (see Figure).Changes (%) in global pancreas T2* were not associated with baseline serum ferritin levels or MRI liver iron concentration (LIC) values but were inversely correlated with % changes in serum ferritin levels (R=-0.199; P<0.0001) and % changes in MRI LIC values (R=-0.255; P<0.0001). A significant positive association was found between % changes in global pancreas and global heart T2* values (R=0.133; P=0.007).At baseline MRI, 169 patients showed an alteration of glucidic metabolism: 32 had impaired fasting glucose, 65 impaired glucose tolerance, and 72 diabetes mellitus. These patients showed significantly higher % changes in global pancreas T2* than patients with a normal glucidic metabolism (33.06±79.48% vs 11.93±59.47%; P=0.003).Conclusions. Our data showed that it is difficult to remove the iron from the pancreas and higher improvements were detected in more heavily loaded patients, with alterations of glucidic metabolism. The reduction in pancreatic iron was paralleled by a decrease in hepatic and cardiac iron. [Display omitted] DisclosuresPepe: Bayer S.p.A.: Other: no profit support; Chiesi Farmaceutici S.p.A: Other: no profit support. Maggio: Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Celgene Corp: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

Predicting Serum Ferritin Levels in Patients with Iron Overload Treated with the Film-Coated Tablet of Deferasirox during the Eclipse Study

Background: The ECLIPSE trial demonstrated that the new film-coated tablet (FCT) deferasirox (DFX) formulation and the dispersible tablet (DT) had similar safety profiles during 6 months of treatment, although fewer patients experienced severe gastrointestinal-related adverse events, and more patients experienced favorable patient-reported outcomes with FCT than with DT (Taher et al. Am J Hematol 2017). Additionally, FCT patients had a greater reduction in serum ferritin (SF) levels from baseline to end of treatment (geometric mean change −431 vs −153 ng/mL in DT patients) despite both groups experiencing similar DFX exposure, which suggests greater efficacy with FCT. In the absence of FCT efficacy data beyond 6 months, we developed a model to predict SF levels in patients from the ECLIPSE trial if they had continued DFX DT or FCT treatment for 6-12 months.Methods: ECLIPSE was a Phase II, randomized, open-label study in which patients with transfusion-dependent thalassemia (TDT) or International Prognostic Scoring System lower-risk myelodysplastic syndromes (MDS) were randomized to receive DFX DT or FCT. Planned doses in iron chelation therapy (ICT)-naïve patients were DT 20 mg/kg/day or FCT 14 mg/kg/day based on equivalent FCT doses being 30% lower than DT due to improved bioavailability. ICT pre-treated patients received either a DT dose equivalent to their pre-washout dose or a planned 30% reduction for FCT. Dose was adjusted based on SF levels and investigator's judgment every 4 weeks for ICT-naïve patients and every 3 months for ICT pre-treated patients (DT ±5-10 mg/kg/day, max 40 mg/kg/day; FCT ±3.5-7 mg/kg/day, max 28 mg/kg/day); dose adjustments for safety reasons were permitted at any time.Models for predicting ICT effect were built and tested based on 12-month data from the controlled registration study ICL670A108 (Porter et al. Eur J Haematol 2008). Most patients from ECLIPSE had received prior ICT; therefore, for the development of the model, this situation was mimicked using ICL670A108 month 3-9 data for fitting, and month 10-12 data for evaluating model prediction quality. The selected model accounted for baseline SF levels, assigned daily DFX dose per arm and patients' body weight, and predicted the ICT effect for up to 12 months if patients had continued with their therapy (DT or FCT). The model was applied to both DT and FCT arms of the ECLIPSE trial and predictions were obtained from individual estimates of each patient.Results:Trial results: 173 patients were randomized 1:1 to DT (n=86) or FCT (n=87); 70 patients in each arm had TDT and 16 patients had MDS (underlying disease missing in 1 FCT patient). Mean±SD age was 34.9±19.3 years, 51% were female and 90% had previously received ICT. Mean±SD actual daily DFX dose over 24 weeks was 27.5±7.7 mg/kg/day (DT) and 20.8±5.4 mg/kg/day (FCT). At baseline, SF geometric mean was 2381 ng/mL (DT) and 2721 ng/mL (FCT).Model prediction: Model diagnostics suggested a close approximation of the ECLIPSE data, as the predicted SF geometric mean during the first 6 months of treatment was similar to the actual SF values observed during the trial (Figure). The model predicted that SF geometric mean values would continue to decrease over the subsequent 6 months with both DT and FCT, reaching 2162 ng/mL (90% confidence interval [CI] 2029-2304) with DT and 2180 ng/mL (90% CI 2054-2311) with FCT after 12 months of treatment. This corresponds to a predicted, relative decrease of 10% with DT and 19% with FCT.Conclusions: The 6-month results of the model were similar to the actual SF values observed during the ECLIPSE trial, and reliably predicted continued ICT effect for months 7-12 if patients had continued with their assigned treatment (DT or FCT). Previous analyses have indicated that improved patient-reported outcomes, especially increased adherence, are significant mediators of the association between treatment with DT vs FCT and SF reduction from baseline over 6 months of treatment (Taher et al. Haematologica 2017;102[s2]:abst P286). According to the predicted results from this model, and at the doses given in this study, patients treated with FCT would have had a greater reduction in SF at 12 months compared with patients treated with DT; although it should be noted that FCT patients had higher baseline SF. This analysis suggests the FCT offers patients an improved DFX formulation, which could be attributed to improved treatment adherence. [Display omitted] DisclosuresTaher:Novartis Pharmaceuticals: Honoraria, Research Funding; Celgene: Research Funding. Weber:Novartis: Employment. Han:Novartis: Employment. Bruederle:Novartis: Employment. Porter:Celegene: Consultancy; Agios Pharmaceuticals: Consultancy, Honoraria; Shire: Consultancy, Honoraria; Bluebird Bio: Consultancy; Novartis: Consultancy, Honoraria, Research Funding.

Plasma Von Willebrand Factor Levels Predict Survival in COVID-19 Patients Across the Entire Spectrum of Disease Severity.

Background: Characterization of reticulo-endothelial activation in COVID-19 may guide treatment. Objectives: To assess reticulo-endothelial activation and its correlation with disease severity and death in patients across the entire spectrum of COVID-19 severity. Methods: Consecutive hospitalized COVID-19 patients were studied, with similar number of patients in each disease severity category. Baseline serum ferritin, sCD163 (macrophage activation markers) and plasma von Willebrand factor (VWF) antigen (endothelial activation marker) levels were studied. Clinical parameters and plasma D-dimer levels were also studied. The study parameters were correlated with COVID-19 severity and survival. Results: The 143 patients (104 males [80%], age 54 [42 – 65] years, median [inter-quartile range]) presented 4 (3—7) days after symptom onset. Thirty-four patients had mild disease, 36 had moderate disease, 36 had severe disease and 37 had critical disease at baseline. With increasing COVID-19 severity, ferritin, sCD163, VWF and D-dimer levels significantly increased at baseline, however, 139 patients had normal sCD163 levels. Of the reticulo-endothelial markers, VWF level independently correlated with COVID-19 severity and with survival. VWF level > 332.6 units/dl correlated with COVID-19 severity (odds ratio [OR]: 2.77 [95% confidence interval (C.I): 1.1 – 6.99], p value: 0.031) and in-hospital death (OR [95% CI]: 29.28 [5.2 – 165], p value < 0.001). Conclusions: Reticulo-endothelial activation markers increased incrementally with worsening COVID-19 severity. Baseline endothelial activation marker (VWF), and not macrophage activation markers, independently correlated with COVID-19 severity and death.

Comparative Study of Intravenous Iron Sucrose Versus Ferric Carboxymaltose for the Treatment of Iron Deficiency Anemia during Pregnancy and Postpartum Period

Objectives: The present study aims at advantages of ferric carboxymaltose therapy over iron sucrose in iron deficiency anaemia of ante natal and postnatal patient. Methods: A prospective observational study was carried out at ACPM medical college during January 2017 to December 2017 for 50 antenatal and 50 postnatal women, total 100 women. Diagnosis of iron deficiency anemia done by proper history taking, examination, peripheral blood smear and blood indices. Baseline haemoglobin and serum ferritin levels were noted on first, eighth, fifteenth and thirtieth day of treatment with iron sucrose or ferric carboxymaltose for randomly selected 50 antenatal and 50 postnatal women. Results: The mean rise of haemoglobin value was 4.3 g/ L for ferric carboxymaltose and 4.0 g/L for iron sucrose in pregnant women. For postpartum women mean rise of haemoglobin was 4.9 g/L after treatment with ferric carboxymaltose and 4.4 g/L for iron sucrose. Conclusion: For the treatment of iron deficiency anaemia in pregnancy as well as postnatal women ferric carboxymaltose is safe, efficient and having many advantages over iron sucrose.

Abnormal iron status is associated with an increased risk of mortality in patients on peritoneal dialysis

Background and aimsIron deficiency is prevalent, but there is limited data about the relationship between iron status and poor outcomes in chronic kidney disease patients undergoing peritoneal dialysis (PD). We aimed to investigate the association between iron status and mortality in PD patients. Methods and resultsThis retrospective study was conducted on incident PD patients from January 2006 to December 2016 and followed up until December 2018. Patients were categorized into four groups according to baseline serum transferrin saturation (percent) and ferritin levels (ng/ml): reference (20–30%, 100–500 ng/ml), absolute iron deficiency (<20%, <100 ng/ml), function iron deficiency (FID) (<20%, >100 ng/ml), and high iron (>30%, >500 ng/ml). Among the 1173 patients, 77.5% had iron deficiency. During a median follow-up period of 43.7 months, compared with the reference group, the FID group was associated with increased risk for all-cause [adjusted hazard ratio (aHR) 1.87, 95% confidence interval (95% CI) 1.05–3.31, P = 0.032], but not cardiovascular (CV) mortality. Additionally, the high iron group had a more than four-fold increased risk of both all-cause and CV mortality [aHR 4.32 (95% CI 1.90–9.81), P < 0.001; aHR 4.41 (95% CI 1.47–13.27), P = 0.008; respectively]. ConclusionFID and high iron predict worse prognosis of patients on PD.

Association between anemia and mortality in hemodialysis patients is modified by the presence of diabetes.

The prevalence and severity of anemia differ between diabetic and non-diabetic patients. We investigated whether the effect of hemoglobin (Hb) on patient outcome was affected by the presence or absence of diabetes among Japanese patients receiving chronic hemodialysis (HD). We enrolled 149,308 patients from a nationwide dialysis registry in Japan at the end of 2012 (mean age, 67.6 ± 12.3years; male, 61.7%; diabetes, 43.5%; median dialysis duration, 65months) who underwent three HD sessions weekly. One-year all-cause and cardiovascular (CV) mortality were assessed using Cox regression analysis and competing-risks regression analysis. We used multiple imputation to deal with missing covariate data. Baseline Hb and serum ferritin levels were independently associated with all-cause and CV mortality. In non-diabetic patients, a significantly higher risk for all-cause mortality compared to the reference group (10 to 11g/dL) was observed in patients with Hb < 8g/dL (hazard ratio (HR): 1.266; 95% confidence interval (CI) 1.097-1.460) and 8 to 9g/dL(HR: 1.153; 95% CI 1.030-1.290). On the other hand, diabetic HD patients in the same Hb category group did not have increased risk of all-cause mortality. We found that non-diabetic HD patients had an increased risk of all-cause mortality if they had lower Hb levels, whereas the effect of Hb levels on mortality was attenuated in diabetic HD patients. These data suggest that the association between Hb levels and mortality rate could be different between diabetic and non-diabetic HD patients.

Baseline and follow-up serum ferritin level as a prognostic factor in coronavirus disease 2019-infected patients: a single-center experience

Objective In the past few months, WHO declared coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 as a major pandemic, with increasing number of discovered cases and mortalities in all countries. Up till now, there are a lot of controversial data on its pathogenesis, possible complications, prognostic factors, and available preventive and/or therapeutic options. A series of fast growing research studies are being conducted aiming at studying prognostic criteria that may predict the disease severity and possible outcomes and hence plan of management either home or hospital management. Patients and methods Our cohort study included 73 COVID-19-confirmed positive cases by nasopharyngeal swab/reverse transcriptase PCR to evaluate correlation between serum ferritin levels (baseline and follow-up samples at day 7), as well as C-reactive protein levels and severity of clinical presentation of COVID-19-infected patients. Results Our results have demonstrated a statistically significant difference between mild (n=40) and moderate cases (n=33) regarding baseline ferritin level (P=0.00); however; no significant difference was detected among ferritin changes during the course of the disease (P=0.744), and also, no statistically significant difference in ferritin changes was found among mild and moderate severity groups (P=0.942). Finally, the only significant predictors of clinical severity were baseline ferritin and C-reactive protein levels according to multivariate analysis model (P=0.014 and =0.000, respectively). Conclusions The current study added further evidence to suggest baseline serum ferritin as an index of severity in COVID-19 and could have a prognostic effect; however, we cannot rely on follow-up serum ferritin during treatment and the course of the disease to predict outcome of the disease, and it may be misleading.

Effect of Ischemic Preconditioning on Marathon-Induced Changes in Serum Exerkine Levels and Inflammation.

Participation in a long-distance run, e.g., marathon or ultramarathon, continues to increase. One side effect of long-distance running is excessive inflammation manifested by the rise in inflammatory cytokine levels. We here aimed to elucidate the effects of 10-day ischemic preconditioning (IPC) training on marathon-induced inflammation and to evaluate the role of serum-stored iron in this process. The study involved 19 recreational runners taking part in a marathon. IPC training was performed in the course of four cycles, by inflating and deflating a blood pressure cuff at 5-min intervals (IPC group, n = 10); the control group underwent sham training (n = 9). The levels of inflammatory and others markers (FSTL-1, IL-6, IL-15, leptin, resistin, TIMP-1, OSM, and LIF) were measured before and 24 h after training; and before, immediately after, and 24 h and 7 day after the marathon. The 10-day IPC training increased serum leptin levels. IL-6, IL-10, FLST-1, and resistin levels were increased, while TIMP-1 levels were decreased in all runners after the marathon. The changes were significantly blunted in runners from the IPC group compared with the control group. Baseline serum iron levels correlated with IL-6 and FSTL-1 levels; serum ferritin correlated with IL-6, FSTL-1, and resistin levels after the marathon. Conversely, serum TIMP-1 levels inversely correlated with serum iron levels. Although not evident at baseline, IPC training significantly reduced marathon-induced inflammation. In addition, the reduced responsiveness and attenuation of running-induced inflammation were inversely related to baseline serum iron and ferritin levels.

Serum ferritin and ECOG performance status predict the response and improve the prognostic value of IPSS or IPSS-R in patients with high-risk myelodysplastic syndromes and oligoblastic acute myeloid leukemia treated with 5-azacytidine: a retrospective analysis of the Hellenic national registry of myelodysplastic and hypoplastic syndromes.

Background:5-azacytidine (5-AZA) improves survival of patients with higher-risk myelodysplastic syndromes (MDSs) and oligoblastic acute myeloid leukemia (AML); however, predictive factors for response and outcome have not been consistently studied.Methods:This study of the Hellenic MDS Study Group included 687 consecutive patients with higher-risk MDS and oligoblastic AML treated with 5-AZA.Results:The International Prognostic Scoring System (IPSS) revised version (IPSS-R), Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 or 1 versus ⩾2) and baseline serum ferritin (SF) levels > 520 ng/ml were shown to independently predict response to 5-AZA. In the survival analysis, the IPSS and IPSS-R risk classification systems along with the ECOG PS and SF levels > 520 ng/ml proved to be independent prognosticators for overall survival (OS), as well as for leukemia-free survival (LFS). Next, we built new multivariate models for OS and LFS, incorporating only ECOG PS and SF levels besides IPSS or IPSS-R risk classification systems. Thereby, the new modified IPSS and IPSS-R risk classification systems (H-PSS, H-PSS-R) could each discriminate a low, an intermediate and a high-risk patient group regarding OS and LFS. The H-PSS and H-PSS-R proved to be better predictors of OS than their previous counterparts as well as the French prognostic score, while the most powerful OS predictor was the new, H-PSS-R system.Conclusions:ECOG PS and SF levels > 520 ng/ml independently predict response to 5-AZA, OS and LFS. Their incorporation in the IPSS and IPSS-R scores enhances these scores’ predictive power in 5-AZA-treated higher-risk MDS and oligoblastic AML patients.