scholarly journals Management of Transfusional Chronic Iron Overload: Focus on Deferasirox

2009 ◽  
Vol 1 ◽  
pp. CMT.S1970
Author(s):  
Federica Pilo ◽  
Anna Angela Di Tucci ◽  
Laura Dessì ◽  
Emanuele Angelucci
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Iron Chelator ◽  
Red Cell ◽  
Current Standard ◽  
Deferoxamine Mesylate ◽  
Clinical Consequences ◽  
Oral Iron Chelator

Most patients with hereditary or chronic acquired anemias are dependent on regular red cell transfusions. Untreated iron overload from transfusions is responsible for morbidity and mortality in patients with thalassemia major. However, clinical consequences of parenchymal iron overload have been reported not only in thalassemia major but also in patients with myelodysplastic syndrome. The current standard in iron chelation therapy is deferoxamine mesylate (Desferal®). Deferasirox is the first oral iron chelator approved in the Europe Union for use in patients with transfusional iron overload with different diseases. The aim of this review is to examine the properties and management of Deferasirox.

Consequent Iron Chelation Therapy in Patients with Low Risk Myelodysplastic Syndrome Leads to up-Regulation of .CXCL12, JAK2 and HSF2: Possible Link Between Iron Chelation and Improvement of Erythropoiesis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2787-2787
Author(s):  
Florian Nolte ◽  
Martin Neumann ◽  
Ouidad Benlasfer ◽  
Sandra Heesch ◽  
Eckhard Thiel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Janus Kinase ◽  
Refractory Anemia ◽  
Iron Chelation Therapy ◽  
Oral Iron Chelator

Abstract Abstract 2787 Poster Board II-763 Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and an increased risk of evolution to acute myeloid leukemia. The majority of MDS patients will depend on regular transfusions of packed red blood cells (PRBC) during their course of disease due to symptomatic anemia. Since recurrent transfusions of PRBC will result in iron overload with the risk of damage of organs such as heart, endocrine glands and the liver, consequent iron chelation therapy (IC) became an important element of supportive care in MDS patients. Recently, the availability of the oral iron chelator deferasirox provides a convenient management of iron overload in MDS. Since intensive IC has been shown to improve hematopoiesis in iron overloaded patients we performed gene expression profiling on patients with low or intermediate MDS prior and after IC, to elucidate wheter IC leads to alteration of genes involved in hematopiesis, in particular in erythropoiesis. Heparinized bone marrow samples were obtained after informed consent from 6 MDS patients (2 refractory anemia, 4 refractory anemia with ringed sideroblasts) upon initial diagnosis of iron overload (prior IC) and after a period of 1 year of iron chelation (after IC) with the oral iron chelator deferasirox. CD34+ hematopoietic progenitor as well as CD71+ erythroid progenitor cells were isolated by high gradient magnetic cell separation (Miltenyi Biotech, Bergisch Gladbach, Germany). RNA was extracted from CD34+ cells and CD71+ cells using TRIzol reagent (Invitrogen, Life Technologies, Grand Island, NY) according to the manufacturer's protocol. Quality controlled RNA was hybridized according to the standard Affymetrix protocol to HG-U133 Plus 2.0 microarrays. Data analysis was performed using the Gene Spring Software version 4.0 (Silicon genetics, San Carlos, CA). Restrictions were set as follows: only genes that were ‘present' in at least 75% of samples were used for further analyses, genes were considered as ‘differentially expressed' when they showed at least 3 fold change between the different groups. Statistical significance was calculated by non-parametric t-test, with P < 0.05. In a first step we compared gene expression patterns of CD71+ cells in MDS patients prior and after IC. In total 106 probe sets representing unique genes, hypthetical proteins and open reading frames matched the restriction settings. In an intensive survey on these genes we identified several genes that have been associated with erythropoiesis including Stromal derived factor-1 (CXCL12), Janus kinase 2 (JAK2), and Heat shock transcription factor 2 (HSF2). To exclude that these changes in gene expression where due to the natural course of the disease in specific patients, we compared gene expression of CD71+ cells from patients after IC to an independent test set of CD71+ MDS samples (n=12). Interestingly, we still found an aberrant expression of these genes, indicating that the observed gene expression changes were related to the IC in these patients rather than to the natural course of diesease. However, we were not able to find an altered expression of these genes in CD34+ progenitor cells prior and after IC, suggesting that the effect on gene expression is restricted to CD71+ cells. Iron overload is an inevitable side effect of regular blood transfusions in MDS patients. Intensive IC has been shown to improve erythropoiesis in iron overloaded patients. We found, that IC results in upregulation of Stromal derived factor-1, Janus kinase 2 and Heat shock transcription factor 2 all of them known to regulate hematopoiesis. Moreover, HSF2 and JAK2 have been closely involved in regulation of erythropoiesis. JAK2 deficiency has been shown to result in abrogated erythropoiesis and therefore increase of JAK2 expression after iron chelation might link IC to improvement of erythropoiesis and subsequently decrease of transfusion requirement in some patients receiving IC. Disclosures: Hofmann: Novartis Oncology, Nürnberg, Germany: Research Funding.

scholarly journals Endocrine complications

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Vincenzo De Sanctis
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Membrane Lipids ◽  
Survival Rates ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Cellular Iron ◽  
Active Iron ◽  
Bone Changes ◽  
Endocrine Complications

More than five decades ago, thalassemia major (TM) was fatal in the first decade of life. This poor prognosis changed since the survival rates started to increase progressively thanks to the implementation of continuous and significant improvement of diagnostic and therapeutic methods, consisting mainly of an intensive transfusion program combined with chelation therapy and imaging methods. Regular red blood cell (RBC) transfusions eliminate the complications of anemia, compensatory bone marrow expansion, bone changes and splenomegaly, restore the physiological growth throughout childhood and extend survival. The most serious disadvantage of life-saving transfusions is the inexorable accumulation of iron within tissues. Iron is physiologically stored intracellularly in the form of ferritin, a protein whose synthesis is induced upon the influx of iron. When the storage capacity of ferritin is exceeded, pathological quantities of metabolically active iron are released intracellularly in the form of hemosiderin and free iron within an expanded labile pool. This metabolically active iron catalyzes the formation of free radicals, which damage membrane lipids and other macromolecules, leading to cell death and eventually organ failure. Other factors contributing to the variability of cellular iron overload are: a) the cell surface transferrin receptors and the capacity of the cells to deploy defence mechanisms against inorganic iron; b) individual susceptibility to iron toxic effect; c) the development of organ(s) damage secondary to persisting severe iron overload in the years preceding iron chelation therapy; and d) liver disorders, chronic hypoxia and associated endocrine complications. Multi-transfused thalassemia major (TM) patients frequently develop severe endocrine complications mainly due to iron overload, anemia, and chronic liver disease, which require prompt diagnosis, treatment and close follow-up by specialists.

Iron Chelation Therapy in Transfusion Dependent Patients with Thalassemia and Minimal Liver Iron Load

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4270-4270
Author(s):  
Antonios Kattamis ◽  
Konstantinos Stokidis ◽  
Theoni Petropoulou ◽  
Dimitra Kyriacopoulou ◽  
Polyxeni Delaporta ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Iron Overload ◽  
Research Funding ◽  
Chelation Therapy ◽  
Combined Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Liver Iron ◽  
Iron Load ◽  
Low Levels

Abstract Abstract 4270 Background: Recent advances in the treatment of iron overload in patients with transfusion- dependent thalassemia have dramatically changed iron related morbidity and mortality. Intensive chelation therapy by using combination therapy or monotherapy at high doses had led to total clearing of the iron in many patients. The best approach for chelation treatment in patients with low levels of iron overload is debatable. Patients and Methods This study included all the patients with thalassemia major with minimal liver iron overload, followed in our unit. More precisely, to be eligible for this observational study, the patients needed to have liver iron concentration (LIC) <1.5 mg Fe/gram dry weight tissue, defined by MRI, and to have at least a subsequent MRI evaluation after this time. The mean observation time, which was the time between the two MRIs, was 16.9±5.2 months. Results Fourty five patients (22 females, 30 non-splemectomized, 21 HCV seropositive, mean age: 31±5.6 years) have reached minimal levels of iron overload in any time point after 2004. Thirty one of them have been treated with combined therapy of desferrioxamine (DFO) and deferiprone (DFP) and 5, 6 and 3 with monotherapy of deferasirox (DFX), DFP and DFO, respectively. After reaching these levels, 42% of the patients changed therapy, with the most frequent change being from combined therapy to monotherapy (15 patients). Baseline ferritin levels at the time of the first MRI range from 43 to 4336 ng/ml (median 230 ng/ml) and they were not affected by spleen, gender or HCV status. Baseline LIC (mean 1.2 ± 1.7 mgFe/g.d.w.) correlated well with ferritin levels (Spearman's rho = 0.47, p<0.005), as did ferritin changes to LIC changes (Spearman's rho = 0.67, p<0.005). The results on the follow up evaluation, stratified according to the actual treatment, are shown in the table Deferiprone was less efficacious in controlling both LIC and ferritin levels compared to combination therapy (p=0.016 and 0.031, respectively). Fifteen out of 17 patients treated with DFP showed an increase in LIC, despite using the recommended dose. Six out of 9 patients treated with DFX, most at a low dose, showed an increase in LIC. There were no differences in changes in the cardiac parameters (LVEF, cardiac T2*) in between treatment groups. The efficiency of DFP and DFX, which represents the ratio of iron excreted to the theoretical maximum of iron that could be bound by the chelators, was calculated at 1.8±0.9 % and 15.2 ± 3.6 %, respectively. Conclusions Current iron chelation therapy regimens are able to render iron load-free many patients with thalassemia major. As iron accumulation from transfusions continues, a fine balance needs to be found in which neither worsening of iron overload nor toxicity from excessive dose of iron chelators will occur. This study showed that at low levels of iron overload both combination therapy and DFX can control iron accumulation, whether monotherapy with DFP may be insufficient to achieve iron balance in many patients. The dose of the chelators needs to be adjusted according to the needs and the clinical course of the patients, which can be predicted by the trend of the ferritin levels. Furthermore, it should be kept in mind that at low levels of iron overload, the iron chelators' efficiency may be lower than previously described. Disclosures: Kattamis: NOVARTIS ONCOLOGY: Honoraria, Research Funding, Speakers Bureau; APOPHARMA: Honoraria. Ladis:NOVARTIS ONCOLOGY: Honoraria, Research Funding; APOPHARMA: Honoraria, Research Funding.

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.

Clinical Effectiveness of Iron Chelation Therapies in Syrian Patients with β Thalassemia Major: Suboptimal Clinical Outcomes and High Prevalence of Iron Overload

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1719-1719
Author(s):  
Youssef A Lama ◽  
Hanan Touma ◽  
Khawla AlKeba ◽  
Osama Maksoud
Keyword(s):  
Combination Therapy ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Clinical Effectiveness ◽  
Thalassemia Major ◽  
Iron Chelation Therapy ◽  
Ferritin Concentration ◽  
Therapeutic Outcomes ◽  
High Prevalence

Abstract Background Thalassemia is the most prevalent autosomal abnormality in the population of Syria. In 2013, the total number of registered thalassemia patients is 8300. Disease prevalence is reinforced by the high rate of consanguineous marriages especially in the rural regions of this Middle Eastern and Mediterraneancountry. Regular blood transfusions and iron chelation therapy (ICT) have significantly improved survival and reduced morbidity of patients withβ thalassemia major (BTM). Although ICTs are provided free of charge by the government to all (BTM) patients, adequate monitoring of therapeutic outcomes is lacking, and cardiac complications still represent significant morbidity and remain the leading cause of mortality. Objective This study aimed at evaluating the prevalence of poor chelation in Syrian patients with BTM, and assessing the effectiveness of different iron chelation regimens provided by the National Thalassemia Program. Methods We conducted a single-centered study encompassing two phases; i) a retrospective chart review of serum ferritin levels of all female and male patients (≥ 3y) with (BTM) receiving iron chelation regimens (mono- or combination therapy) in 2009 and 2010; and ii) a 15 month prospective observational study to evaluate the effectiveness of desferrioxamine (DFO) monotherapy (at a dose of 40-50 mg/kg given over 8–10 h on 5-7 d/week), versus DFO (at the same dose used for DFO monotherapy) in combination with deferiprone (DFP) (at a dose of 75 mg/kg/day) [DFO+DFP] in patients received prior monotherapy with DFO but had poor response. Endpoints were defined as reducing iron stores in iron overloaded patients and improving cardiac function assessed by left ventricular ejection measurements using Doppler Echocardiogram. Statistical analysis of data sets was performed using Prism Graphpad, version 5. Results A total of 493 records of all patients registered at the National Thalassemia Centre in Homs were evaluated. 280 (56.8%) of these patients were diagnosed with BTM, and 245/280 (87.5%) were receiving iron chelation therapy. The average age was 11.35 ± 5.69 year-old (mean ± SD), age range [3-32 year], and male-to-female sex ratiowas 102:103. 39% of the patients were administered DFO, 30% and 10% received oral deferasirox (DFX) and deferiprone (DFP) respectively, whereas 21% received a combination of [DFO + DFP]. The average ferritin concentration of the study population was 3954.89 ± 1431.37 [range from 1362 to 8656] ug/l in 2009, and 4038.22 ± 1572.49 [range from 1173 to 8210] ug/l in 2010. Strikingly, 98% of patients had iron overload; [15% mild, 35% moderate and 48% severe] in 2009, and [12.3% mild, 42.5% moderate and 45.2% severe] in 2010. Patients on DFX had the lowest ferritin concentrations when compared with these of their peers on the DFO and [DFO + DFP] regimens (P=0.0001 and P=0.02 respectively). Patients of DFX also had the lowest percentage of sever iron overload (31%) in comparison with 58%, 51%, and 40% in patients on DOF, [DFO+DFP], and DFP respectively. In the prospective observational phase of our study, several comparative assessments were conducted. The combination of [DFO+DFP] reduced ferritin concentration by 14% from a mean baseline concentration of 4662.4 ±1266.17 to 3697.1 ±1547.9 (μg/l) after the study 15 month follow up period (P=0.0006), whereas DFO alone was ineffective. Cardiac function decreased by a percentage of (-4.74 ± 12.89) from 68.64%±6.97% to 60.98%±7.22% in patients on DFO (p= 0.0001) and from 67.39%±6.49% to 63.91%±8.51% in patients receiving combination therapy (p= 0.031). Mean decrease was greater in DFO regimen (-10.53 ± 11.89) than that seen in patients on combination therapy (-4.74 ± 12.89) (p= 0.035). Conclusions This study reveals aspects of the current status of ICT outcomes in Syria. Our results prove high prevalence of iron overload in patients with BTM despite their receiving ICTs free of charge. Patients are not achieving target serum ferritin thresholds despite chronic treatment with DFO for iron overload. This may suggest its poor clinical effectiveness within the real-world, and necessitates active measures to improve patients’ compliance. The underlying causes of these suboptimal therapeutic outcomes of all ICT regimens should be further investigated, and the cost-effectiveness of ICTs should be reconsidered by decision makers. Disclosures: No relevant conflicts of interest to declare.

Transfusion-Related Iron Overload: A Covert Risk Of Supportive Cancer Care

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3656-3656
Author(s):  
Anushka Jaffer ◽  
Rebecca Barty ◽  
Erin Jamula ◽  
Grace Wang ◽  
Yang Liu ◽  
...  
Keyword(s):  
Iron Overload ◽  
Cancer Patients ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Adult Patients ◽  
Iron Chelation Therapy ◽  
Not Given ◽  
Screening Practices ◽  
Rbc Transfusion

Abstract Background Chronic transfusion support plays a key role in survival and quality of life for patients with hematological disorders. However, transfusion-related iron overload (TRIO) is a significant cause of morbidity and mortality in these patients.Adequate iron overload (IO) screening and use of iron chelators, if necessary, is now standard practice in chronically transfused individuals such as hemoglobinopathy patients. Screening practices for IO for patients receiving multiple red blood cell (RBC) transfusions for other reasons (e.g. cancer) are unknown. Objective This two part study aimed to detect pediatric (Jaffer et al., 2012) and adult populations at risk for TRIO and to evaluate and compare current screening practices. Methods Children (≤ 18 years) and adults (> 18 years) receiving at least 1 RBC transfusion from January 1, 2008 to December 31, 2011 at a tertiary care academic institution were identified using a transfusion registry database. Only those receiving chronic RBC transfusions were included in the study. Chronic transfusion was defined as ≥20 units of RBC or ≥ 20 RBC transfusions dosed at 15ml/kg within 12 consecutive months where transfusions were not given in the setting of an operating room, trauma or surgical procedures, not given 7 days prior/post-surgical procedures and not all given in one day. An adjudicator resolved study inclusion ambiguity. The analysis excluded hemoglobinopathy patients. Medical records were reviewed to collect patient demographics, diagnosis, and to evaluate IO screening practices and frequency of iron chelation therapy. Results A total of 343 patients met the eligibility criteria: 27 pediatric and 316 adult patients, with mean ages of 8.1 years (SD 5.7) and 62 years (SD 12.6), respectively. Table 1 summarizes demographics, number of transfusions, and IO screening and results. Ferritin levels were checked for 12 (44%) pediatric and 227 (72%) adult patients: 2 (17%) pediatric and 30 (13%) adult patients had values<500 μg indicating no further TRIO screening was required. In the pediatric population, 81% had a cancer diagnosis, and just under a third were tested for ferritin, whereas 64% of the adults had cancer, with nearly two-thirds tested for ferritin. A statistically significant difference was observed in the percentage of pediatric and adult cancer patients screened for IO. Of those cancer patients screened, ferritin level > 500 occurred in 71% of pediatric and 85% of adult patients, with an iron chelator reported in 1 adult. Total RBC transfusions ranged from 20 to 44 with a median of 26.5 for pediatrics and 20 to 176 with a median of 31 for adults. Conclusion Despite high rates of RBC transfusion, screening for TRIO was inconsistent. Although information regarding reasons for not screening for TRIO or not treating with chelation therapy was not collected, the possibilities include a lack of awareness of the risk of TRIO and lack of access to ferriscan and/or to oral iron chelator in Canada for conditions other than hemoglobinopathy and a select subset of MDS cases. Considering TRIO presents an additional, yet unidentified, co-morbidity of cancer therapy and that the therapy (e.g. anthracyclines) may potentiate the end organ effect of TRIO, it is vital to develop strategies to evaluate cancer patients at risk for TRIO and ensure they have access to appropriate iron chelation therapy. Research is needed to explore the comorbidities associated with failure to treat TRIO and to identify barriers to treatment so cancer patients can receive optimal care. Disclosures: Leber: Novartis Canada: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau. Heddle:Canadian Blood Services and Health Canada: Research Funding.

scholarly journals EFFECT OF IRON OVERLOAD AND IRON CHELATORS ON ANTI-MÜLLERIAN HORMONE LEVEL IN EGYPTIAN FEMALE PATIENTS WITH TRANSFUSION DEPENDENT β-THALASSEMIA

2017 ◽  
Vol 10 (4) ◽  
pp. 263
Author(s):  
Noha Sayed Hamed
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Chelation ◽  
Significant Negative Correlation ◽  
Thalassemia Major ◽  
Iron Chelator ◽  
Female Patients ◽  
Excess Iron ◽  
Thalassemia Minor ◽  
Iron Chelator Deferoxamine

Objective: This work aims to determine the effect of iron overload on serum anti-müllerian hormone (AMH) levels in females subjected to transfusion-dependent β-thalassemia by measuring serum ferritin and to investigate the effects of iron chelation therapy including oral deferiprone and subcutaneous deferoxamine in the management of transfusion-related iron overload together with reproductive function.Methods: 90 female patients with thalassemia major (TM), thalassemia intermedia (TI) and thalassemia minor (T minor) were selected to investigate AMH by ELISA and ferritin by IRMA.Results: Serum AMH level was lower in female patients with transfusion dependent β-thalassemia than in T minor also, Ferritin was 25 fold more in TM compared to T minor (3088.0±2497.6 ng/ml vs. 120.3±36.2 ng/ml). There was significant negative correlation of AMH with ferritin in TM (r =-0.949; P<0.001*), in TI (r =-0.378; P =0.039*) and in T minor (r =-0.754; P<0.001*). The iron chelator, deferoxamine had significantly higher ferritin and lower AMH in TM and TI than deferiprone.Conclusion: the results demonstrated that females with TM and TI were found to have lower serum AMH levels than T minor and inversely related to the serum ferritin levels in all thalassemic groups. Also, it demonstrated that deferiprone was more efficient than deferoxamine in removing excess iron and reduced the deleterious effect of excess iron to the reproductive system, which leads to fertility preservation of female patients with transfusion–dependent β-thalassemia.Keywords: Anti-müllerian hormone, Ferritin, Iron overload, β-thalassemia, Deferoxamine, Deferiprone.

scholarly journals A case of transfusion independence in a patient with myelodysplastic syndrome using deferasirox, sustained for two years after stopping therapy

2015 ◽  
Vol 22 (2) ◽  
pp. 128 ◽  
Author(s):  
D. Sanford ◽  
C.C. Hsia
Keyword(s):  
Myelodysplastic Syndrome ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Red Blood Cell Transfusion ◽  
Transfusion Independence ◽  
Clinical Complications ◽  
Increased Risk ◽  
History Of

Patients with myelodysplastic syndrome (mds) experience clinical complications related to progressive marrow failure and have an increased risk of developing acute myeloid leukemia. Frequent red blood cell transfusion can lead to clinical iron overload and is associated with decreased survival in mds patients. Iron chelation therapy reduces markers of iron overload and prevents end-organ damage.Here, we present the case of a patient with lowrisk mds with transfusional iron overload. He was treated for 2 years with an oral iron chelator, deferasirox, and after 12 months of treatment, he experienced a hemoglobin increase of more than 50 g/L, becoming transfusion-independent. He has remained transfusion-independent, with a normal hemoglobin level, for more than 2 years since stopping chelation therapy. Hematologic and erythroid responses have previously been reported in mds patients treated with iron chelation. The durability of our patient’sresponse suggests that iron chelation might alter the natural history of mds in some patients.

Once-Daily Treatment with the Oral Iron Chelator ICL670 (Exjade®): Results of a Phase II Study in Pediatric Patients with β-Thalassemia Major.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3614-3614 ◽  
Author(s):  
Antonio Piga ◽  
Renzo Galanello ◽  
Maria Loreta Foschini ◽  
Antonella Zappu ◽  
Elena Bordone ◽  
...  
Keyword(s):  
Iron Overload ◽  
Pediatric Patients ◽  
Phase Ii Study ◽  
Pediatric Population ◽  
Thalassemia Major ◽  
Iron Chelator ◽  
Once Daily ◽  
Group 2 ◽  
Oral Iron Chelator ◽  
Group 1

Abstract ICL670 (deferasirox) is an investigational, once-daily oral iron chelator which has been shown to effectively and selectively mobilize tissue iron in adults with transfusional hemosiderosis. The safety and tolerability of ICL670 administered over 48 weeks were investigated in an open-label Phase II study in 4 centers in France and Italy in 40 pediatric patients aged 2–17 years with β-thalassemia major and transfusional iron overload. The patients were stratified into two age groups: Group 1 (n=20), aged 2 to 11 years (mean 6.7 years); Group 2 (n=20), aged 12 to17 years (mean 14.1 years). Seven of the Group 1 patients were aged <6 years. Since this was the first study with ICL670 in a pediatric population, a conservative starting dose of 10 mg/kg once daily was given, irrespective of the degree of iron overload at baseline. The primary objectives of the study were the safety and tolerability of ICL670. Secondary objectives included pharmacokinetics and liver iron content (LIC) which was measured non-invasively by magnetic susceptometry using a Superconducting QUantum Interference Device (SQUID) at baseline, 4, 12, 24, 36 and 48 weeks. Dose adjustments based primarily on changes in LIC were made in 14 patients in Group 1 (in 9 patients to 15 mg /kg and 5 patients to 20 mg/kg after a median of 39 weeks) and in 7 patients in Group 2 (all to 20 mg/kg after a median of 28 weeks). ICL670 was well tolerated also after the dose increases. Mild, transient gastrointestinal complaints (nausea, vomiting, abdominal pain or diarrhea) during the first days of therapy were the principal drug-related adverse events (AEs). A single patient discontinued ICL670 due to a suspected drug-related AE (a generalised skin rash of moderate severity). No audiometry or ophthalmologic abnormalities were detected and no patient developed neutropenia, thrombocytopenia or arthralgias. Baseline levels of WBCs, platelets, serum creatinine and trace elements were unchanged after 48 weeks of therapy. The table summarizes the main efficacy variables using an intent-to-treat analysis. The average number of transfusional events during the study was 14.8 and 16.4 in Groups 1 and 2, respectively, equivalent to a mean of 0.48 and 0.45 mg/kg/day of iron. At the doses tested in this study, ICL670 was well tolerated in this pediatric population which included very young children. Dose increases were performed relatively late in the study and this, together with the fact that an ICL670 dose of 10 mg/kg is at the lower end of the effective dose range for heavily transfused patients, may explain the mild increase in iron burden over 48 weeks. Based on these encouraging preliminary results, ongoing studies are investigating the safety and efficacy of ICL670 in children at daily doses of up to 30 mg/kg. Group 1 (N=20) Group 2 (N=20) Baseline mean (SD) 24 weeks mean (SD) 48 weeks mean (SD) Baseline mean (SD) 24 weeks mean (SD) 48 weeks mean (SD) LIC (mg/g dw) 6.2 (2.5) 6.6 (2.6) 7.9 (2.5) 5.7 (2.2) 5.9 (2.7) 6.4 (2.1) Serum ferritin g/L) μ) 2146 (1422) 2435 (2376) 2876 (1063) 1867 (711) 2599 (757) 3016 (1075)

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