Hepcidin Levels and Erythropoietin Alfa Resistance In Patients with Chemotherapy Induced Anemia (CIA)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3216-3216
Author(s):  
M. Schipperus ◽  
B. Rijnbeek ◽  
M. Reddy ◽  
W. Li ◽  
E. Vercammen ◽  
...  
Keyword(s):  
Predictive Accuracy ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Baseline Serum ◽  
Reactive Protein ◽  
Lack Of Information ◽  
Significant Difference ◽  
Serum Hepcidin ◽  
Almost All ◽  
Erythropoietin Alfa

Abstract Abstract 3216 Introduction: Hepcidin is a key regulator of iron metabolism and is a central mediator of anemia associated with inflammation. Hepcidin has previously been associated with resistance to ESAs in renal anemia and may also be a potential mediator of ESA resistance in chemotherapy-induced anemia (CIA). We therefore assessed hepcidin in a cohort of patients with CIA who received erythropoietin alfa (EPREX, Janssen-Cilag, Ltd.) as part of a post-approval safety study. Patients and Methods: All subjects were anemic (defined as baseline Hb ≤11 g/dL) and almost all patients had one of the following malignancies: breast, ovarian, gastric and pancreatic cancer, myeloma. Patients were receiving standard doses of EPREX for management of CIA. Patients with anemia secondary to iron deficiency (defined as transferrin saturation ≤ 20%) were excluded from study enrollment. Serum erythropoietin was not assessed as a condition of eligibility. Hemoglobin (Hb) response was defined as an increase of ≥ 1 g/dL through week 4. Baseline serum hepcidin levels were measured retrospectively using a hepcidin C-ELISA. The relationships between hepcidin, Hb, iron status (serum iron, ferritin, transferrin saturation), C-Reactive Protein (CRP) (a marker of inflammation and surrogate for IL-6 activity) and Hb response were evaluated. Results: Among 51 anemic patients with a median age of 56 (range 25–72), 42 were Hb responders. None of the patients studied received blood transfusions during the first 4 weeks of treatment. No significant difference in baseline hepcidin or CRP levels was found between the Hb responders and non-responders; hepcidin 129.43 ng/mL (9.5-722.4) versus 210.7 (9.9-399.6) and CRP 47.1 nmol/L (0-428.6) versus 46.0 (2.1-1145.7) respectively. All subjects who had a decrease in Hb through week 4 were tumor non-responders. Baseline hepcidin levels were inversely correlated with baseline Hb (p = 0.04) but did not predict for Hb response. Neither did baseline CRP nor iron status. Adjusting hepcidin for iron status did not improve predictive accuracy. No significant correlation was found between CRP change at week 4 and Hb response. A correlation was found between baseline hepcidin and week 4 CRP (p = 0.0004) but not with baseline CRP levels. Conclusions: Baseline hepcidin was not predictive of Hb response to ESA therapy. Hepcidin change may be a better predictor and warrants further evaluation. Lack of information on baseline erythropoietin levels is a significant limitation of this study. Correlation with additional markers (e.g., soluble transferrin receptor, inflammatory markers like IL-6) will also be important to fully determine the role of hepcidin as a predictor for EPO resistance in settings of chronic inflammation. Disclosures: Rijnbeek: Johnson & Johnson: Employment. Reddy:Johnson & Johnson: Employment. Li:Johnson & Johnson: Employment. Vercammen:Johnson & Johnson: Employment. Cornfeld:Johnson & Johnson: Employment.

scholarly journals The evaluation of iron status in hemodialysis patients.

1996 ◽  
Vol 7 (12) ◽  
pp. 2654-2657 ◽  
Author(s):  
S Fishbane ◽  
E A Kowalski ◽  
L J Imbriano ◽  
J K Maesaka
Keyword(s):  
Iron Deficiency ◽  
Serum Ferritin ◽  
Marginal Utility ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Hemodialysis Patients ◽  
Mean Cell Volume ◽  
Distribution Width ◽  
Baseline Serum ◽  
Significant Difference

Effective treatment of anemia in hemodialysis patients requires ongoing monitoring of iron status. The purpose of this study was to determine levels of commonly used iron indices predictive of iron deficiency in this population. Forty-seven patients with baseline serum ferritin levels < 600 ng/mL were treated with intravenous iron dextran (INFeD; Schein Pharmaceutical Inc., Florham Park, NJ), 1000 mg over ten hemodialysis treatments. Patients whose hematocrit value increased by 5% or who had a 10% decrease in their erythropoietin dose by 2 months were classified as having iron deficiency (N = 31; 66%). All other subjects were classified as having adequate iron (N = 16; 34%). There was no statistically significant difference in baseline serum ferritin, transferrin saturation, mean cell volume, mean cell hemoglobin content, or red cell distribution width between the two groups. Receiver operator curves demonstrated that none of the iron indices had a high level of utility (both sensitivity and specificity > 80%). Two tests had marginal utility, serum ferritin at a level of < 150 ng/mL, and transferrin saturation < 21%. It was concluded that because of the tests' marginal utility, they should only be interpreted in the context of the patient's underlying erythropoietin, responsiveness. In patients who are responsive to erythropoietin, a transferrin saturation value < 18% or serum ferritin level < 100 ng/mL should be used to indicate inadequate iron. When erythropoietin resistance is present, transferrin saturation of < 27% or serum ferritin < 300 ng/mL should be used to guide iron management.

Relationship Between Epoetin Alfa (EPO) Treatment and Serum Hepcidin Levels in Anemic Patients with Rheumatoid Arthritis (RA)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3450-3450
Author(s):  
Victor Moyo ◽  
Robert Kersting ◽  
Mark Westerman ◽  
Wayne Langholff ◽  
Ruchi Rastogi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Serum Ferritin ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Oral Iron ◽  
Serum Transferrin ◽  
Baseline Serum ◽  
Iron Restriction ◽  
Serum Hepcidin ◽  
The Impact

Abstract Introduction: Some patients treated with EPO and oral iron supplementation respond poorly to EPO, possibly due to inflammation-induced iron sequestration. In response to inflammation, hepcidin, a hormone secreted by the liver, binds to and downregulates ferroportin, the principal cellular iron exporter. In turn, ferroportin downregulation leads to sequestration of iron in absorption sites within duodenal enterocytes, hepatocytes, and in macrophages that break down senescent red blood cells and normally recycle iron back into circulation. This sequestration results in reduced amounts of plasma iron that is bio-available for erythropoiesis. Patients with rheumatoid arthritis (RA), malignancies, or infections frequently manifest inflammatory-associated anemia and elevated hepcidin levels. Objective: To assess the impact of EPO treatment on hepcidin levels in patients with RA. Methods: Serum hepcidin levels and iron status were analyzed from a randomized, double-blind, placebo-controlled, investigational study of 29 patients with RA treated with either EPO or Placebo for 20 weeks. Serum hepcidin levels were measured at baseline and at the end of study. Serum transferrin saturation, serum ferritin, serum transferrin receptor (sTfr) levels and hemoglobin (Hb) concentrations were also measured. Patients with baseline Hb ≤11 g/dL were treated with EPO starting doses of 20,000 U subcutaneously (SQ) once weekly (QW) that could be titrated up to 40,000 U SQ QW. Oral iron was administered to keep the sTfr index <1.5. Iron restriction adequate to hinder erythropoiesis was defined by a transferrin saturation of <16%. Serum hepcidin levels of ≥300 ng/mL were considered elevated. Hematologic response to EPO was defined by achieving a Hb of ≥12 g/dL or a ≥2 g/dL increase in Hb from baseline to the end of study. Results: Iron restriction was noted in 5/15 (33%) EPO-treated patients and in 2/14 (14%) receiving Placebo. Hepcidin levels were elevated in 10/15 (67%) EPO-treated patients and in 5/13 (38%) receiving Placebo. There was a strong correlation between baseline serum hepcidin and serum ferritin levels (R= 0.5598 P=0.0019), but not serum transferrin saturation. Eleven of 15 (73%) EPO-treated patients had a Hb response compared to one of 14 (7%) receiving Placebo. Mean hepcidin levels decreased significantly from baseline in the EPO-treated patients (−155.6±186.6 EPO, 90.28±83.1 Placebo, P<0.01). As shown in the diagrams below, serum hepcidin levels appeared to decrease in EPO-treated patients, but not in those receiving Placebo, while Hb levels increased in EPO-treated patients but not in the patients receiving Placebo. Conclusion: EPO treatment may effectively elicit Hb response in patients with RA and may be associated with suppression of inflammation-induced serum hepcidin levels. Further study is warranted in conditions associated with inflammation, such as cancer and chronic renal failure, in which EPO is used to treat anemia. FIG 1. SERUM HEPCIDIN LEVELS (ng/mL) FIG 1. SERUM HEPCIDIN LEVELS (ng/mL) FIG 2. Change from Baseline to End of Study FIG 2. Change from Baseline to End of Study

scholarly journals THE ASSOCIATION BETWEEN LEVELS OF HEPCIDIN, IRON STATUS AND MICRO-INFLAMMATION MARKERS AMONG HAEMODIALYSIS

2019 ◽  
Author(s):  
Ebtesam Ahmad Mufadhal ◽  
Fairouz Kaid Al-Showafi ◽  
Hassan A. Al-Shamahy ◽  
Ebtesam Mhdi Al-zabidi
Keyword(s):  
Peer Review ◽  
Serum Iron ◽  
Iron Status ◽  
Control Group ◽  
Inflammation Markers ◽  
C Reactive Protein ◽  
Maintenance Haemodialysis ◽  
Reactive Protein ◽  
Serum Hepcidin ◽  
E Mail

Hepcidin is a polypeptide that regulates iron homeostasis and could serve as an indicator of functional iron deficiency in patients with end-stage renal disease (ESRD); this may also aid in the assessment of patient's response to erythropoietin (EPO). Erythropoietin is a cytokine glycoprotein secreted by the kidney in response to cellular hypoxia; it stimulates the production of red blood cells (erythrocytes) in the bone marrow. The present study was aimed to investigate serum levels of hepcidin, iron status and inflammation markers such as C-reactive protein (CRP) in patients with ESRD on maintenance HD and to observe the correlation of serum hepcidin with conventional iron and inflammatory markers. A total of 59 patients on maintenance HD were enrolled; 29 age and sex-matched healthy subjects were included as controls. Laboratory tests including complete blood count, creatinine, urea, albumin, BUN, serum hepcidin, serum ferritin, serum iron and CRP were performed. The serum hepcidin levels was measured by a competitive enzyme-linked immunosorbent assay (C-ELISA). Serum hepcidin levels were significantly higher in patients with ESRD than in the control group (63.7±47.4 ng/mL: 11.5± 26.3 ng/mL respectively P<0.001). The hemoglobin and serum iron levels in the patient group were significantly lower than in the control group. Higher feritine levels were found in hemodialysis patients (448.5±710 ng/mL): ( 98.3±83 ng/mL) of controls (P =0.01). A positive and significant correlation was observed between the values of serum hepcidin and CRP.  Serum hepcidin and high-sensitivity C-reactive protein levels were significantly higher in maintenance haemodialysis patients (case=21.2±28.6 mg/L:control=2.9±2.7 mg/L, P=0.001). In conclusion, higher hepcidin levels are found in ESRD patients and serum hepcidin levels are associated with iron status and micro-inflammation (defined as hsCRP < 6mg/l, in maintenance haemodialysis patients). Also, our findings suggest that hepcidin might play a role in the pathophysiology of anemia associated with chronic diseases as ESRD. As well as, ELISA method for measuring serum hepcidin should facilitate the routine measurement of hepcidin in clinical practice. Peer Review History: UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication st0ge: 8.5/10 Reviewer(s) detail: Name: Hebatallah Ahmed Mohamed Moustafa Affiliation: Heliopolis University Cairo, Egypt E-mail: [email protected]   Name: Dr. Heba M. Abd El-Azim  Affiliation: Damanhour University, Egypt E-mail: [email protected] Comments of reviewer(s):

scholarly journals Increased Serum Transferrin Saturation Is Associated with Lower Serum Transferrin Receptor Concentration

1999 ◽  
Vol 45 (12) ◽  
pp. 2191-2199 ◽  
Author(s):  
Anne C Looker ◽  
Mark Loyevsky ◽  
Victor R Gordeuk
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Transferrin Receptor ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Reference Interval ◽  
Serum Transferrin ◽  
Reactive Protein ◽  
Serum Transferrin Receptor ◽  
Health And Nutrition

Abstract Background: Serum transferrin receptor (sTfR) concentrations are increased in iron deficiency. We wished to examine whether they are decreased in the presence of potential iron-loading conditions, as reflected by increased transferrin saturation (TS) on a single occasion. Methods: We compared sTfR concentrations between 570 controls with normal iron status and 189 cases with increased serum TS on a single occasion; these latter individuals may be potential cases of iron overload. Cases and controls were selected from adults who had been examined in the third National Health and Nutrition Examination Survey (1988–1994) and for whom excess sera were available to perform sTfR measurements after the survey’s completion. Increased TS was defined as &gt;60% for men and &gt;55% for women; normal iron status was defined as having no evidence of iron deficiency, iron overload, or inflammation indicated by serum ferritin, TS, erythrocyte protoporphyrin, and C-reactive protein. Results: Mean sTfR and mean log sTfR:ferritin were ∼10% and 24% lower, respectively, in cases than in controls (P &lt;0.002). Cases were significantly more likely to have an sTfR value &lt;2.9 mg/L, the lower limit of the reference interval, than were controls (odds ratio = 1.8; 95% confidence interval, 1.04–2.37). Conclusion: Our results support previous studies that suggested that sTfR may be useful for assessing high iron status in populations.

scholarly journals Serum Hepcidin Level as a Marker of Iron Status in Children with Cystic Fibrosis

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Monika Kałużna-Czyż ◽  
Urszula Grzybowska-Chlebowczyk ◽  
Halina Woś ◽  
Sabina Więcek
Keyword(s):  
Cystic Fibrosis ◽  
Iron Status ◽  
Full Blood Count ◽  
Control Group ◽  
Hepcidin Level ◽  
Significant Difference ◽  
Serum Hepcidin ◽  
Liver Markers ◽  
Group Control Group ◽  
Active Inflammation

Introduction. Iron deficiency is common in patients with cystic fibrosis. Conventional iron status markers are often abnormal in patients with CF, reflecting inflammation and/or infection, rather than actual iron stores. The aim was to evaluate serum hepcidin levels against selected iron status markers, assuming that hepcidin may be a more sensitive indicator of iron management in patients with active inflammation, such as those with CF. Material and Methods. 46 children with cystic fibrosis and 31 healthy controls were enrolled. Hepcidin concentration was evaluated, along with the following other blood assays: full blood count, Fe, ferritin, transferrin, TIBC, liver markers, and CRP. Results. Higher ferritin and CRP levels as well as lower TIBC levels significantly predicted hepcidin levels in the study group, control group, and the entire sample. There was no significant difference in hepcidin levels between the patients and controls. Children with exacerbations had significantly higher hepcidin levels than those with stable disease. These findings support the serum hepcidin level as useful in assessing iron status in children with cystic fibrosis. It may also be useful in early detection and monitoring of treatment of exacerbations.

Serum Soluble Transferrin Receptor in Heterozygous β-Thalassaemia: Application in the Diagnosis of Iron Deficiency and as Hematologic Marker of Erythroid Activity According to Thalassaemic Genotypes (β0 vs β+).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3828-3828
Author(s):  
Jose Manuel Calvo-Villas ◽  
María Francisca Zapata ◽  
Ivan Alvarez ◽  
Silvia de la Iglesia ◽  
Jorge Cuesta ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Transferrin Receptor ◽  
Biochemical Parameters ◽  
Iron Status ◽  
Direct Sequencing ◽  
Saturation Index ◽  
Transferrin Saturation ◽  
Soluble Transferrin Receptor ◽  
Iron Deficient ◽  
Significant Difference

Abstract Although an increased level of serum soluble transferrin receptor (sTfR) have been found in both heterozygous β-thalassaemia patients with iron deficiency and in those with more severe genotype (β0), it is not a useful marker of iron deficiency status associated to β-thalassaemia. The aim of this study was to analyse the use of two biochemical parameters (sTfR and sTfR/log of ferritin ratio) to determine the iron status and to evaluate the degree of erythropoietic activity in a group of 221 β-thalassaemic heterozigotes patients (155 β0 and 66 β+). Serum ferritin and transferrin saturation index were measured in order to establish the iron status. Of the whole group, 51 patients were iron defficient (βthal-ID) while the remaining 170 were iron sufficient (βthal-IS). Based on the combination of β-thalassaemia genotype and iron status, patients were classified into four subgroups: β0thalassaemia and iron-sufficient (β0thal-IS) (n=124); β0thalassaemia and iron-deficient (β0thal-ID) (n=31); β+thalassaemia and iron-sufficient (β+thal-IS) (n=46); β+thalassaemia and iron-deficient (β+thal-ID) (n=20). 258 healthy and 56 iron-deficient individuals were used as controls. All the haematological parameters were measured by using analyzer Coulter® GEN-S™. Haemoglobins A2 (Hb A2) and F (HbF) were analysed by high performance liquid chromatography and molecular analysis was performed by real-time PCR and direct sequencing techniques. Chemical, inmunoturbidimetrical and nephelometric methods were used to measure iron status as well as sTfR. Comparison of haemalogical and biochemical parameters between subgroups was performed by using the t-student test and correlation analysis was calculated by using least-squares regression model. Mean sTfR level obtained was 2.63 ± 0.8 mg/dL and 2.57 ± 1.1 mg/dL in βthal-ID and βthal-IS patients respectively (p=0.783). Soluble transferrin receptor showed a positive correlation with HbA2, HbF and reticulocyte count values in βthal-IS patients (r=0.208 [p<0.05], r=0.440 [p<0.0001] and r=0.393 [p<0.00001] respectively) while it did not reach a significant correlation in βthal-ID patients. Mean sTfR/log sFt ratio was 2.75 ± 1.6 and 1.34 ± 0.5 in βthal-ID and βthal-IS patients (p<0.001). Interestingly, sTfR level was significantly higher in β0thal-IS patients when compared with β+thal-IS patients (2.76 ± 0.9 vs 1.42 ± 0.4) (p<0.001) as a result of an increased globin chains imbalance related to the β0 genotype. In the other hand, in the comparison between β0thal-ID and β+thal-ID subgroups neither sTfr level (2.71 ± 0.7 vs 2.40 ± 1.1) (p=0.417) nor sTfR/log sFt ratio (2.93 ± 1.7 vs 2.24 ± 1.3) (p=0.371) showed significant difference. In summary, sTfR/log sFt ratio is a valid parameter for diagnosis of iron deficiency associated to heterozygous β-thalassaemia. Unlike the findings observed in β-thalassaemic heterozigotes with normal iron status, sTfR level is not useful to evaluate the genotype severity in those with iron deficiency. Consequently, iron status should be determined before using sTfR as a parameter to provide a reliable estimation of the ineffective erythropoiesis related to the severity of β-thalassaemia genotypes.

scholarly journals Iron Age or New Age: Ironing out the Diagnosis of Anaemia of Inflammation from Iron Deficiency Anaemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3354-3354
Author(s):  
Nicola J Svenson ◽  
Russell Patmore ◽  
Heidi J Cox ◽  
James R Bailey ◽  
Stephen Holding
Keyword(s):  
Iron Deficiency ◽  
Serum Ferritin ◽  
Serum Iron ◽  
Iron Status ◽  
Diagnostic Testing ◽  
Transferrin Saturation ◽  
Oral Iron ◽  
Gastrointestinal Disorders ◽  
Serum Hepcidin ◽  
Iron Parameters

Abstract Introduction Iron deficiency anaemia (IDA) and anaemia of chronic inflammation (AI) are the most prevalent causes of iron related anaemia in subjects with gastrointestinal disorders contributing significantly to morbidity and mortality. Diagnosis of IDA and AI is not always straight forward and currently a combination of several serum parameters (ferritin, transferrin, transferrin saturation, iron and C-reactive protein) is required. Subjects with a mixed aetiology can be difficult to interpret using traditional serum parameters, particularly in the presence of an inflammatory process. Hepcidin (a 25 amino-acid peptide hormone) in conjunction with reticulocyte haemoglobin equivalent (RetHe) has the potential to differentiate IDA from AI and in cases of mixed aetiology replacing the traditional laboratory parameters (serum iron, CRP, transferrin saturation and ferritin). Aim The aim of the study was to evaluate the performance of a commercially available ELISA assay and investigate whether hepcidin and RetHe can differentiate AI from mixed aetiology. Method The study investigated 77 patients with gastrointestinal disorders associated with anaemia in a secondary care setting using a traditional pathway of 6 tests (figure 1): Complete Blood Count (CBC), Reticulocytes, serum ferritin, CRP, transferrin, serum Iron. Hepcidin concentration was measured using a commercially available ELISA method (DRG Diagnostic GmbH, Marburg, Germany), CBC and RetHe using a Sysmex XE-2100 CBC analyser, iron parameters and CRP using Beckman Coulter platforms. Results Hepcidin correlated well with ferritin R2 = 0.79, p<0.0001. The results were compared to traditional parameters with Receiver Operator Curves (ROC) used to determine diagnostic cut off concentrations (table 1). Table 1. Sensitivity and specificity of serum ferritin and serum hepcidin used to determine diagnostic cut off values. Selected cut off values IDA AI Serum ferritin 30.0µg/L Sensitivity 83% Specificity 64% Sensitivity 55% Specificity 75% Serum hepcidin 8ng/mL Sensitivity 73% Specificity 72% Sensitivity 70% Specificity 67% Serum hepcidin 40ng/mL Sensitivity 98% Specificity 32% Sensitivity 25% Specificity 91% Ferritin was unable to distinguish IDA from AI in mixed aetiology situations. This gives rise to a new proposed 2 step pathway (figure 2) using 3 tests: CBC, RetHe and hepcidin differentiating IDA from AI in mixed aetiology cases indicating the cause of the anaemia. The RetHe value can then be used to predict the response to oral iron. Conclusion Serum hepcidin may not yet replace serum ferritin as the preferred iron status marker, but in conjunction with RetHe it may distinguish mixed aetiology subjects. This offers the potential development of a clearer clinical pathway for investigation of difficult subjects, including reduction in the number of tests required during anaemia investigations and shorter diagnosis times. The advantage of hepcidin together with RetHe over traditional iron parameters is both as a real time marker of iron status and an indication of likelihood of response to iron therapy. The patient would benefit from a shorter recovery time, unnecessary testing, reduction in ineffective treatment and overall reduction in costs. Figure 1. Current diagnostic testing pathway using 6 independent tests with serum ferritin used as the primary indicator of iron stores. Figure 1. Current diagnostic testing pathway using 6 independent tests with serum ferritin used as the primary indicator of iron stores. Figure 2. Suggestion of a new 2 step diagnostic testing pathway with serum hepcidin as the primary indicator and reticulocyte haemoglobin equivalent as the predictor of iron deficiency and response to oral iron. Figure 2. Suggestion of a new 2 step diagnostic testing pathway with serum hepcidin as the primary indicator and reticulocyte haemoglobin equivalent as the predictor of iron deficiency and response to oral iron. Disclosures Patmore: Janssen: Honoraria; Gilead: Honoraria.

Siltuximab Treatment Increases Hemoglobin (Hb) Levels: Preliminary Results From a Prospective Phase 1 Study In Refractory Solid Tumors

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5150-5150
Author(s):  
R. Kurzrock ◽  
E. Angévin ◽  
S. Cohen ◽  
J. Van Laethem ◽  
B. Rijnbeek ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Research Funding ◽  
Serum Iron ◽  
Binding Capacity ◽  
Iron Status ◽  
Phase 1 ◽  
Transferrin Saturation ◽  
Maximum Increase ◽  
Baseline Serum ◽  
Clinically Significant

Abstract Abstract 5150 Introduction: Siltuximab is a chimeric monoclonal antibody with high affinity for the inflammatory cytokine, IL-6, which is currently being studied in hematologic, solid malignancies and multicentric Castleman's disease (MCD). In addition to representing a therapeutic target, IL-6 is reported to play a key role in the etiology and symptoms of anemia of cancer. A possible mechanism is through up-regulation of hepatic production of hepcidin, the central iron-regulatory hormone. Siltuximab treatment has previously been shown to be associated with clinically significant Hb increases in MCD (a disorder caused by deregulated IL-6 production) and renal cell carcinoma. We have prospectively studied the Hb response in the context of a phase I study with siltuximab in patients with advanced solid tumors. Patients and Methods Siltuximab was administered intravenously to patients with any advanced solid tumor at increasing dose levels (2.8 or 5.5 mg/kg every 2 weeks, 11 or 15 mg/kg every 3 weeks). Hepcidin (C-ELISA), Hb, CRP (marker for inflammation) and iron status (serum iron, ferritin, transferrin saturation, total iron binding capacity) were measured at baseline and serially during treatment. IL-6 was not measured since interference of the drug with assay performance prevents accurate measurement of bioactive IL-6. The relationships between these biomarkers and Hb response (defined as a maximum Hb increase of ≥1 g/dL during treatment) were evaluated. Results: Forty-four pts (18 colorectal, 12 ovarian, 5 pancreatic, 9 other) received a median of 3 siltuximab cycles (range 1 – 25). Eight patients were excluded from analysis because they received blood transfusions or ESAs. There were no objective tumor responses (CR or PR). Baseline Hb ranged from 9.4–15.3 g/dL (median 12.2). All 36 evaluable patients had an increase in Hb (median 1.35 g/dL; range 0.1–3.2). Eleven (31%) patients had a maximum increase of ≥2 g/dL. Maximum Hb levels did not exceed the upper limit of normal. Baseline hepcidin (median 118.6 ng/mL; range 9.5–493.3) was positively correlated with baseline CRP (median 13.6 mg/L; range 0.42–152.0) (p<0.05) and ferritin (median 346 pmol/L; range 74.2–8543.1) (p<0.05) but not with baseline Hb or Hb response. For subjects with a Hb response of more than 2 g/dL an association was found with Day 8 hepcidin (p = 0.03) when controlled for baseline serum iron. Early hepcidin percentage change was not correlated with Hb response. Conclusion: Siltuximab treatment was associated with clinically meaningful Hb response in this moderately anemic refractory cancer population. The exact mechanism of action remains uncertain, however correlation with additional markers (e.g., soluble transferrin receptor, inflammatory markers such as IL-6) might also be important to identify patients most likely to respond to treatment and should be evaluated further in randomized trials. Disclosures: Kurzrock: Johnson & Johnson: Research Funding. Angévin:Johnson & Johnson: Research Funding. Cohen:Johnson & Johnson: Research Funding. Van Laethem:Johnson & Johnson: Research Funding. Rijnbeek:Johnson & Johnson: Employment. Vermeulen:Johnson & Johnson: Employment. Tromp:Johnson & Johnson: Employment. Li:Johnson & Johnson: Employment. Reddy:Johnson & Johnson: Employment. Cornfeld:Johnson & Johnson: Employment. Tabernero:Johnson & Johnson: Research Funding.

scholarly journals Low serum iron is associated with anemia in CKD stage 1–4 patients with normal transferrin saturations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pei-Hua Yu ◽  
Ming-Yen Lin ◽  
Yi-Wen Chiu ◽  
Jia-Jung Lee ◽  
Shang-Jyh Hwang ◽  
...  
Keyword(s):  
Serum Iron ◽  
Reference Group ◽  
Binding Capacity ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Reactive Protein ◽  
Ckd Stage ◽  
Adjusted Logistic Regression ◽  
Stage 1 ◽  
Low Serum

AbstractLow transferrin saturation (TSAT), calculated by serum iron divided by total iron-binding capacity (TIBC), indicates iron deficiency. Because malnutrition and inflammation are associated with low TIBC in chronic kidney disease (CKD), TSAT might not reflect iron status or risk for anemia. We examined whether low serum iron was a risk factor for anemia in CKD patients with normal TSAT. Thus we compare the risk for anemia in 2500 CKD stage 1–4 patients divided by TSAT (cutoff: 20%) and serum iron (cutoff: 70 μg/dL in men, 60 μg/dL in women). Our results confirmed low TIBC (< 200 μg/dL) was associated with hypoalbuminemia and high C-reactive protein. In fully-adjusted logistic regression, both “normal TSAT low iron” and “low TSAT low iron” groups were associated with baseline anemia (hemoglobin < 11 g/dL) (odds ratios (OR) 1.56; 95% confidence interval (CI) 1.13–2.16 and OR 2.36; 95% CI 1.76–3.18, respectively) compared with the reference group (normal TSAT normal iron). Sensitivity tests with different cutoffs for TSAT and iron also showed similar results. In patients without anemia, both groups were associated with anemia after 1 year (OR 1.69; 95% CI 1.00–2.83 and OR 1.94; 95% CI 1.11–3.40, respectively). In conclusion, CKD stage 1–4 patients with normal TSAT but low serum iron are still at risk for anemia.

scholarly journals ANALYSIS OF RET-HE IN CHRONIC KIDNEY DISEASE PATIENTS AT DR.WAHIDIN SUDIROHUSODO HOSPITAL, MAKASSAR

2019 ◽  
Vol 25 (1) ◽  
pp. 7
Author(s):  
Febrina Rovani ◽  
Asvin Nurulita ◽  
Mansyur Arif
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Iron Homeostasis ◽  
Complete Blood Count ◽  
Binding Capacity ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Test Method ◽  
Pathology Laboratory ◽  
Significant Difference

Anemia, the common feature of Chronic Kidney Disease (CKD), is a multifactorial process due to disordered erythropoiesis and iron homeostasis. Determining the cause of anemia is important for adequate management. A bone marrow biopsy using Prussian Blue as the gold standard for diagnosis is invasive and more complicated to perform. Reticulocytes-Hemoglobin (Ret-He) a new parameter that indicates the hemoglobin content in reticulocytes is faster, easier, and less expensive. This study aimed to analyze the Ret-He in determining the iron status in patients with CKD. A cross-sectional study was held in the Clinical Pathology Laboratory of Dr. Wahidin Sudirohusodo Hospital Makassar during April-August 2016. Forty-five (45) samples were tested for iron serum (Fe), Total Iron Binding Capacity (TIBC), and Complete Blood Count (CBC) ordered by the physician. Reticulocytes-Hemoglobin was tested using the whole blood. Subjects were around the age of 19-71 years, no significant difference was found between numbers of males and females (46.6% and 53.3%). Hemoglobin median was 8 (5.0-15) g/dL, Fe 50 (6-177) U/mL, TIBC 183 (73-379), Transferrin Saturation (Tsat) 25 (5-95)%. Spearman correlation test method showed significant correlations between Ret-He and iron serum r=0.533, p <0.001, Ret-He and TIBC r=0.321 p=0.031 Ret-He and transferrin saturation r=0.416 p=0.019. The Mann-Whitney method showed no significant difference of Ret-He in both groups (Tsat <20% and >20%). There were significant correlations between Ret-He and iron, Ret-He and TIBC, Ret-He and transferrin saturation. A further study using larger samples is suggested to consider factors affecting the result of Ret-He.

Sign in / Sign up

Export Citation Format

Share Document