Overview of Current Treatment Regimens in Iron Chelation Therapy

2009 ◽  
Vol 02 ◽  
pp. 56
Author(s):  
Aryeh Shander ◽  
Joseph D Sweeney ◽  
◽  
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Physiological Mechanism ◽  
Iron Chelation ◽  
Current Treatment ◽  
Iron Toxicity ◽  
Red Blood Cell Transfusion ◽  
Iron Chelation Therapy ◽  
Transfusion Therapy ◽  
Treatment Regimens

As humans have no physiological mechanism for the elimination of excess body iron, chronic red blood cell transfusion therapy, which is necessary for the treatment of a number of transfusion-dependent anemias, inevitably results in iron overload. Cumulative iron overload can lead to iron toxicity with organ dysfunction and damage, particularly affecting the liver and heart. Once iron overload has been identified in patients with transfusion-dependent anemias, it should be treated with chelation therapy to prevent and limit iron toxicity. Iron chelation with deferoxamine, deferiprone, and deferasirox has been demonstrated to reduce iron burden and the associated risk for morbidity and mortality from iron toxicity; however, there are important differences among these iron chelators.

scholarly journals Durable Red Blood Cell Transfusion Independence in a Patient with an MDS/MPN Overlap Syndrome Following Discontinuation of Iron Chelation Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Harpreet Kochhar ◽  
Chantal S. Leger ◽  
Heather A. Leitch
Keyword(s):  
Blood Cell ◽  
Iron Overload ◽  
Red Blood Cell ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Red Blood Cell Transfusion ◽  
Favorable Effect ◽  
Iron Chelation Therapy ◽  
Transfusion Independence ◽  
Rbc Transfusion

Background. Hematologic improvement (HI) occurs in some patients with acquired anemias and transfusional iron overload receiving iron chelation therapy (ICT) but there is little information on transfusion status after stopping chelation.Case Report. A patient with low IPSS risk RARS-T evolved to myelofibrosis developed a regular red blood cell (RBC) transfusion requirement. There was no response to a six-month course of study medication or to erythropoietin for three months. At 27 months of transfusion dependence, she started deferasirox and within 6 weeks became RBC transfusion independent, with the hemoglobin normalizing by 10 weeks of chelation. After 12 months of chelation, deferasirox was stopped; she remains RBC transfusion independent with a normal hemoglobin 17 months later. We report the patient’s course in detail and review the literature on HI with chelation.Discussion. There are reports of transfusion independence with ICT, but that transfusion independence may be sustained long term after stopping chelation deserves emphasis. This observation suggests that reduction of iron overload may have a lasting favorable effect on bone marrow failure in at least some patients with acquired anemias.

Matched-Pair Analysis of 186 MDS Patients Receiving Iron Chelation Therapy or Transfusion Therapy Only.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1747-1747 ◽  
Author(s):  
Frank Fox ◽  
Andrea Kündgen ◽  
Kathrin Nachtkamp ◽  
Corinna Strupp ◽  
Rainer Haas ◽  
...  
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Ferritin Level ◽  
Iron Chelation ◽  
Matched Pair ◽  
Iron Chelation Therapy ◽  
Transfusion Therapy ◽  
Matched Pair Analysis ◽  
Advisory Boards ◽  
Pair Analysis

Abstract Abstract 1747 Poster Board I-773 Introduction Patients with MDS, especially those with a lower-risk type of disease, are prone to develop iron overload, partly due to increased duodenal iron resorption triggered by ineffective erythropoiesis, but mainly as a consequence of chronic transfusion therapy. Transfusion dependency is clearly associated with a decreased likelyhood of survival. It is less clear how far that association is attributable to the severity of the underlying bone marrow disease as opposed to toxic effects of iron overload. A large retrospective study from Spain recently showed that iron overload (serum ferritin >1000 ng/μl) was a significant prognostic factor for overall survival and leukemia-free survival. On multivariate analysis, the impact of iron overload was independent of transfusion requirement. If iron overload itself has an adverse effect on survival, iron chelation (IC) should do the opposite. This was indeed suggested by a partly retrospective and partly prospective observational study from France which showed a strong survival benefit from chelation therapy in patients with lower-risk MDS. We gathered that short of a prospective phase III trial, a retrospective matched-pair analysis might provide the best available data to identify a survival effect of iron chelation therapy in MDS. Methods Our matched-pair analysis included 93 patients with various types of MDS undergoing long-term chelation therapy, for whom we were able to identify 93 matched partners in the Düsseldorf MDS Registry (n=3552) who received supportive care only (SC, excluding iron chelation). Pairs were matched according to age at diagnosis, gender, MDS type according to WHO classification, and IPSS score. All 186 patients had iron overload, defined as serum ferritin of at least 500ng μl. Patients were followed up until death or until June 30, 2009. Results Median age was 63 yrs in the iron chelation group and 67 yrs in the supportive care group (p=n.s.). In both groups, the distribution among WHO types was as follows: 4 RA, 7 RARS, 41 RCMD, 22 MDS with del(5q), 8 RAEB I, 7 RAEB-II, 4 CMML-I. Both groups showed the following IPSS risk profile distribution: 37% low risk, 46% intermediate-I, 14% intermediate-II, and 3% high risk. Median ferritin level in the chlelated group was 1954 (498-7580), median ferritin level in the non-chelated group was 945 (508-5800). In the IC group, patients received the following chelators: deferoxamine (n=54), deferiprone (n=5), deferasirox (n=32), deferoxamine or followed by deferasirox (n=12), and deferoxamine plus deferiprone (n=4). The mean duration of the iron chelation was 28 months for Deferasirox and 39 months for Deferoxamine. Among patients receiving iron chelation therapy, 52% died in the observation period, as compared with 58% in the SC group. Median survival time in the IC group was 74 months vs. 49 months in the SC group (p=0.002). There was no significant difference regarding the risk of evolution into acute myeloid leukemia (AML). The cumulative risk of AML transformation between the IC group and the SC group was 10% vs. 12% two years after diagnosis, and 19% vs. 18% five years after diagnosis (p=0.73). Conclusions Our data support the idea that iron chelation therapy results in improved overall survival of MDS patients, mainly by reducing the risk of non-leukemic death. Since this was a retrospective analysis of registry data, we cannot determine exactly which clinical complications (e.g. cardiac events or infections) were diminished. This goal must be achieved by a well-designed prospective clinical trial. Our results do not seem to confirm that iron chelation therapy decreases the risk of leukemic transformation. However, such an effect may require elimination of labile plasma iron in order to suppress oxidative stress. LPI levels were not available in this retrospective matched-pair analysis but should be included in prospective studies. Disclosures Fox: Novartis: Consultancy, Honoraria, Participation in advisory boards in desferasirox trials, Speakers Bureau. Germing:Novartis: Honoraria, Research Funding, Speakers Bureau. Gattermann:Novartis: Honoraria, Participation in Advisory Boards on deferasirox clinical trials.

Iron Chelation Therapy in CAPD: A New and Effective Treatment of Iron Overload Disease in Esrd Patients

1983 ◽  
Vol 3 (2) ◽  
pp. 99-101 ◽  
Author(s):  
Glen H Stanbaugh ◽  
A. W, Holmes Diane Gillit ◽  
George W. Reichel ◽  
Mark Stranz
Keyword(s):  
Peritoneal Dialysis ◽  
Iron Overload ◽  
End Stage Renal Disease ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelation Therapy ◽  
Peritoneal Dialysate ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

A patient with end-stage renal disease on CAPD, and with massive iron overload is reported. This patient had evidence of myocardial and hepatic damage probably as a result of iron overload. Treatment with desferoxamine resulted in removal of iron in the peritoneal dialysate. On the basis of preliminary studies in this patient it would appear that removal of iron by peritoneal dialysis in conjunction with chelation therapy is safe and effective. This finding should have wide-ranging signficance for patients with ESRD.

scholarly journals Iron Chelation and Ferritin below 500 Mcg/L in Transfusion Dependent Thalassemia: Beyond the Limits of Clinical Trials

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3542-3542 ◽  
Author(s):  
Natalia Scaramellini ◽  
Carola Arighi ◽  
Alessia Marcon ◽  
Dario Consonni ◽  
Elena Cassinerio ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Liver Function ◽  
Iron Overload ◽  
Board Of Directors ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Published Data ◽  
Iron Chelation Therapy ◽  
Iron Intake ◽  
Advisory Committees

Introduction The current therapeutic management of transfusion dependent thalassemia (TDT) is based on regular blood transfusion and iron chelation therapy. Transfusion iron overload remains one of the major causes of morbidity and mortality in these patients because of the accumulation in heart, liver and endocrine glands. Three iron chelators are available in clinical practice: deferoxamine (DFO), deferiprone(DFP) and deferasirox (DFX). Guidelines clearly recommend when to start iron chelation, while discontinuation criteria are not well defined. Authorised product information state that we should consider interrupting DFX if serum ferritin (SF) falls consistently below 500mcg/L. This cut off was arbitrarily determined and there are no studies evaluating the effects of chelators in presence of SF below 500 mcg/L. In our clinical practice at Rare Diseases center of Fondazione IRCCS Ca' Granda Policlinico in Milan we do not completely interrupt iron chelation in TDT patients for SF levels below 500 mcg/L. Aims and methods Aim of our study was to evaluate the appearance of adverse events due to the assumption of iron chelation therapy in those TDT patients who had SF below 500 mcg/L. In this study we retrospectively evaluated renal and liver function from 2008 throughout December 2018 in TDT patients on DFX who presented SF below 500 mcg/L for 24 consecutive months. DFX dose are all expressed with the new tablets formulation dose. We evaluated SF, iron intake, LIC and MIC, renal and hepatic function. .A total of 5076 observations were collected, with 99.5 average per patient. We evaluated the relationships among variables with correlation models with random intercept Results One hundred ninety-two TDT patients are regularly followed at our center. They receive regular transfusion treatment and iron chelation therapy to prevent secondary iron overload. 51 out of 192 patients (32 F, 19 M, aged 44 ± 7 years) treated with DFX presented mean SF below 500 mcg/L for at least 24 consecutive months. Hematological and iron status parameters are described in Table 1. We found a strong correlation between SF and LIC (p<0.001) and for SF<500 mcg/L no hepatic iron overload was observed. Conversely we did not found a correlation between SF and MIC. For SF values below 500 mcg/L there was a minimal increase in creatinine levels, however the mean creatinine values remained within the normal range.Moreover, creatinine variation between two consecutive evaluation was below 0.3 mg/dl, cut off for acute kidney injury. Similar results were observed for liver function. Although a minimal increase of mean ALT value was observed for SF below 500 mcg/L, it remained within the normal range. None of our patient showed ALT level indicative of liver damage (ALT> 10 x upper limit of normal) We evaluated the relation between SF and DFX dose. Mean DFX dose decreases according to SF reduction. However, for SF value < 240 mcg/L, DFX dose remained stable at an average of 14 mg/kg per day. Conclusion According to our preliminary data, administration of DFX in TDT patients in presence of SF below 500 mcg/L is safe. Creatinine and ALT fluctuations, that usually remain within the range of normality, are mild, and transient and do not require specific treatment. Consistently with previously published data by Cohen et al, we show that a mean dosage of DFX of 14 mg/Kg die of film-coated tablet (20 mg/Kg of dispersable formulation) are necessary to balance an iron intake of 0.3 mg/kg die in absence of iron overload. Based on these results we suggest that in TDT patients with a continuous iron intake, iron chelation should be continued even when ferritin is below 500mcg/L. Monitoring of liver and kidney function tests are recommended in patient's follow up, as well as tailoring iron chelation. Disclosures Cappellini: Vifor Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; CRISPR Therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Honoraria; Novartis: Membership on an entity's Board of Directors or advisory committees; Genzyme/Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Motta:Sanofi-Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Effectiveness, Time Utilization and Clinical Outcome of Partial Manual Red Cell Exchange in Patients with Sickle Cell Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2326-2326
Author(s):  
Kevin H.M. Kuo ◽  
David Barth ◽  
Richard Ward
Keyword(s):  
Sickle Cell Disease ◽  
Clinical Outcome ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Venous Access ◽  
Iron Chelation Therapy ◽  
Red Cell ◽  
Cell Disease ◽  
Hemoglobin S

Abstract Abstract 2326 Introduction: Red cell exchange transfusion (RBCX) is used to treat and prevent selected complications from Sickle Cell Disease (SCD) where there is a need to reduce hemoglobin S level, blood viscosity, improve oxygen carrying capacity, and to avoid rapid iron overload from simple transfusions. Partial manual red cell exchange is sometimes employed in the chronic maintenance of low hemoglobin S levels. Data on the efficacy and clinical outcome of SCD patients on partial manual RBCX are limited. Methods: All partial manual RBCX from the University Health Network, a SCD comprehensive care center between April 1st, 2010 and April 30th, 2011 were retrospectively reviewed. Patients were exchanged at a frequency of 4 to 6 weeks where each session consists of two 500cc phlebotomy with an infusion of 500cc normal saline in between the phlebotomies, and transfusion of 2 units of packed red cells (pRBC). The procedure was repeated until pre-RBCX hemoglobin S (HbS) level <50% was reached (for patients without overt stroke for >4 years). Phlebotomy was reduced or omitted during episodes of symptomatic anemia at the discretion of the treating hematologist. Patients with poor venous access had indwelling line with chronic, therapeutic anticoagulation against line-related thrombosis. Results: Nineteen patients (16 HbSS, 2 HbSC, 1 HbSD) totalling 176 exchange sessions were reviewed. Indications for RBCX include primary and secondary stroke prevention (n = 14), recurrent painful vaso-occlusive crises intolerant or refractory to hydroxyurea (n = 3), pulmonary hypertension confirmed on right heart catheterization with hypoxia (n = 1), and prevention of intrahepatic cholestasis in a liver allograft (n = 1). Mean frequency of RBCX was 4.8 weeks (95% CI 3.9, 5.6 weeks). There were 2 transfusion-related (fever, pruritis) and 1 phlebotomy-related (pre-syncope) adverse events. There were 23 partial/cancelled phlebotomy sessions, mostly due to symptomatic anemia. Mean post-RBCX hematocrit was 0.296 (95% CI 0.280, 0.312) and pre-RBCX HbS level was 0.439 (95% CI 0.387, 0.490). Pre-RBCX HbS level of <50% was achieved in 74% of exchanges. Reasons for not achieving the target HbS level include: exchange interval >4.0 weeks, not on any transfusion regime prior to initiating partial manual RBCX, reduced or no phlebotomy in previous session, and non-adherence to treatment. Patients who were adherent to treatment had no recurrent events related to their initial indication for RBCX (one patient has possible Moyamoya formation but no clinically overt stroke), while 3 of the 6 patients who were not adherent had events during the study period (2 had painful vaso-occlusive crisis requiring hospital admission and 1 had new Moyamoya-like changes on cerebral angiogram). It took a median time of 90 minutes to phlebotomize 1,000cc whole blood and 176 minutes to transfuse two units of pRBC. There was no significant difference between the time required to phlebotomize or transfuse via peripheral vein versus an indwelling line (55 vs. 53 minutes/500cc; P = 0.7572 and 88 minutes vs. 88 minutes/unit; P = 0.9859). Eleven patients were also on iron chelation therapy for iron overload from previous simple transfusion, and patients who were adherent to RBCX (n = 7) had either a stable or reduction in ferritin level. Discussion: Patients who are adherent on partial manual RBCX can maintain a pre-RBCX HbS <50% with good clinical outcomes and low rates of adverse events, reduced blood consumption compared to automated RBCX, and obviate the need for ongoing iron chelation in those without pre-existing iron overload. In patients with iron overload, RBCX combined with iron chelation therapy can maintain iron balance. In patients with good peripheral venous access, indwelling lines do not confer an advantage to the speed of phlebotomy or transfusion. Patient with pre-RBCX HbS level >50% may benefit from a single session of automated RBCX to “reset” their HbS level before commencing chronic partial manual RBCX. Further prospective studies will aim to determine the rate of new or progressive silent infarcts and vasculopathy and reduction of iron balance via partial manual RBCX. Disclosures: Kuo: Novartis Canada: Research Funding.

Estimating Iron Burden in Simple Vs. Modified Manual Exchange Transfusions in Pediatric Sickle Cell Patients on Chronic Transfusions

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4850-4850
Author(s):  
Mansi Lalwani ◽  
Mary DeBarr ◽  
Ann O'Riordan Mary ◽  
Connie M Piccone ◽  
Brian W Berman
Keyword(s):  
Iron Overload ◽  
Sickle Cell ◽  
Exchange Transfusion ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Red Cell ◽  
Cell Disease ◽  
Transfusion Therapy ◽  
Packed Red Blood Cells ◽  
Transfusion Protocol

Abstract Abstract 4850 Introduction: Nearly 100,000 Americans are affected by sickle cell disease (SCD), making it one of the most prevalent genetic disorders in the United States. Individuals with SCD exhibit significant morbidity and mortality related to chronic hemolysis, vasculopathy, and vascular occlusion by red cell sickling. Currently, red cell transfusions are a primary therapy for some of the acute and chronic complications of SCD, including prevention and treatment of stroke. The benefits of transfusion therapy are well known; however, transfusional iron overload is an inevitable consequence. Excess iron in the circulation leads to the formation of reactive oxygen species which ultimately causes end-organ damage. It is well established that adult SCD patients with significant iron overload have a higher mortality. As a result, exchange transfusion protocols are utilized to try to decrease overall iron overload. In our center, a modified manual exchange (MME) protocol is used which involves therapeutic phlebotomy of approximately 5–7.5ml/kg followed by the infusion of 15–20ml/kg packed red blood cells. MME is performed in the outpatient setting every 4–6 weeks with a goal hemoglobin S of less than 30%. Objective: The primary objective of our study was to describe the benefits of a MME protocol compared with a simple transfusion protocol in patients experiencing both. The effects of MME versus simple tranfusion on systemic iron overload were evaluated using serum ferritin levels, net transfusion volume, and need for iron chelation therapy. Study Design/Methods: A retrospective chart review was performed on patients with SCD (type SS) less than 18 years of age who were on chronic transfusions and transitioned from a simple to a MME protocol. All patients included were on chronic transfusions for primary/secondary stroke prevention. Exclusion criteria included all patients on automated exchange transfusion protocols and those patients who started iron chelation therapy after January 1, 2008. Demographic as well as clinical and laboratory data were collected on each patient. A simple transfusion was defined as 20ml/kg packed red blood cells transfused every 4–6 weeks. The MME protocol was defined as above. Iron overload was assessed using indicators including net volume of blood transfused, serum ferritin, and the need for iron chelation during both time periods, and differences were calculated. The Wilcoxon signed rank test was used for the change in amount of blood transfused. Slopes of ferritin levels over time were estimated for each transfusion protocol separately using mixed model methods. The need for chelation therapy was tabulated for each patient. Results: A total of six patients were included in the study, 4 boys and 2 girls. Ages ranged from 6–14 years. Four patients had been on chronic transfusions for more than 2 years prior to the start of our study. The mean net volume transfused during simple transfusion and MME was 400ml and 290ml, respectively (p=0.03). The slope of ferritin rise was 0.18 (CI: 0.11, 0.84) for MME and 1.37 (CI: 0.56, 2.17) for simple transfusion. One patient was taken off chelation therapy completely after transitioning to MME and another patient was maintained on low-dose chelation while on MME. Conclusions: MME appears to reduce the amount of blood transfused, slow the rise of ferritin, and potentially reduce the need for additional medication. MME may provide a safe and cost effective approach for delaying or preventing iron overload in patients with sickle cell disease who require long term transfusion therapy. Disclosures: No relevant conflicts of interest to declare.

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