scholarly journals Time to Start Delivering Iron Chelation Therapy in Newly Diagnosed Severe β-Thalassemia

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Susi Susanah ◽  
Ponpon S. Idjradinata ◽  
Nur M. Sari ◽  
Lulu E. Rakhmilla ◽  
Yunia Sribudiani ◽  
...  
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Status ◽  
Transferrin Saturation ◽  
Iron Chelation ◽  
Normal Diet ◽  
Iron Chelation Therapy ◽  
Newly Diagnosed ◽  
Hepcidin Level ◽  
Significant Difference

Background. Iron overload is still a major complication of severe β-thalassemia. Indication to start iron chelation therapy is based on serum ferritin (SF) or transferrin saturation (TS) level or the amount of transfusion. The goal of this study is to analyse the pattern of iron status, the amount of transfusion regarding the time to start iron chelator, and serum hepcidin levels in newly diagnosed severe β-thalassemia. Methods. A prospective cohort study was performed at Hasan Sadikin General Hospital on newly diagnosed severe β-thalassemia patients. Subjects had not received any blood transfusion with normal liver function test, CRP, and IL-6 levels who consumed normal diet according to age. The SF and TS levels indicate iron status, while hepcidin level indicates iron regulator status. Main indicator to start iron chelation therapy when SF level ≥1.000 ng/mL, TS level ≥70%, or after receiving transfusion at least 10 times. Statistical analysis used Mann–Whitney and Spearman. Results. Forty-two newly severe β-thalassemia, 30 (71.4%), were diagnosed before 1 year old, mean 9.9 ± 6.4 months, range 2–24 months. Range amount of transfusion until SF level reached ≥1,000 ng/mL were 4-12 times, mean 7 ± 2 times. Mean SF and TS level at diagnosis were 365.6 ± 194.9   ng / mL and 67.3 ± 22.5 % , while hepcidin level was normal, mean 242.6 ± 58   ng / mL . 36/42 patients have reached SF >1000 ng/mL with amount of transfusion less than 10 times. There was no significant difference of SF, TS, and hepcidin levels when SF >1000 ng/mL in the group with amount of transfusion 7–12 and less than 7 ( p = 0.454 , p = 0.084 , p = 0.765 ), respectively. A significant positive correlation between SF and amount of transfusion was observed ( p < 0.001 ; r = 0.781 ). Conclusion. Iron overload in severe β-thalassemia patients might occur earlier even before they received 10 times transfusion. Hepcidin serum level tends to increase when iron overload just started.

scholarly journals A Randomized Trial on the Safety and Efficacy of Early Start of Iron Chelation Therapy with Deferiprone in Newly Diagnosed Children with Transfusion Dependent Thalassemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1286-1286
Author(s):  
Mohsen Saleh Elalfy ◽  
Vasilios Berdoukas ◽  
Fernando Tricta ◽  
Amira Adly ◽  
Nyeria Hazza ◽  
...  
Keyword(s):  
Adverse Events ◽  
Iron Overload ◽  
Chelation Therapy ◽  
Transferrin Saturation ◽  
Iron Chelation ◽  
Iron Accumulation ◽  
Iron Chelation Therapy ◽  
Newly Diagnosed ◽  
Abdominal Colic

Abstract Iron toxicity is the main risk factor for morbidity and mortality in patients with transfusion-dependent thalassemia. Current practice is to start chelation therapy only after 10-20 transfusions, or when the serum ferritin (SF) level rises above 1,000 μg/L. This delay is aimed at minimizing the risk of chelation toxicity that was observed with the use of deferoxamine in children with low iron stores. Deferiprone has lower affinity for iron than deferoxamine and data from clinical trials on its use in patients without systemic iron overload indicate a safety profile for its use in those conditions. The current trial was designed to evaluate the safety of the early use of low-dose deferiprone in newly diagnosed pediatric thalassemia and to evaluate if it can postpone iron overload. Sixty-four children recently diagnosed with thalassemia major who had begun receiving blood transfusions every 3-4 weeks to keep pre-transfusion Hb above 10 gm/dl, had not yet started iron chelation therapy and had SF ≥ 400 μg/L or transferrin saturation (TSAT) ≥ 70% or labile plasma iron (LPI) ≥ 0.2 µM were randomized to start deferiprone (DFP) at a dose normally considered to be sub-therapeutic (50 mg/kg/day) or no chelation (NC). Age at 1st transfusion was 8.1 ± 1.7 for DFP-treated and 8.1 ± 1.6 months for NC children. The percentage of patients with LPI ≥ 0.6 µM, SF ≥ 1000 μg/L or TSAT ≥ 70% in each study arm was assessed at 6 months and 12 months. Patients with confirmed SF ≥1000 ng/mL were withdrawn from the study and placed on a standard chelation regimen. Results. Two patients (DFP) were lost to follow after baseline measurements, 1 patient (NC) withdrew consent at baseline, and 10 patients (5 DFP, 5 NC) have yet to complete all follow up visits. All NC patients had been removed from the trial prior to completing 7 months of follow-up 12 due to confirmed SF ≥ 1000 μg/L. Mean ± SD time of follow up was 10.4± 4.9 and 5.9 ± 2.5 months for DFP and NC, respectively. Most common adverse events in patients on DFP versus NC were diarrhoea (19% vs 13%, p= 0.73), vomiting (13% vs 13%, p=1.00), abdominal colic (13% vs 13%), increased liver enzymes (6% vs 3%, p=1.00) and neutropenia (neutrophil count between 1,000-1,500 x 109/L) (6% vs 6%). All adverse events were mild in severity and did not require interruption of DFP use. There were no cases of agranulocytosis or of moderate neutropenia, no arthralgia and no serious infections in DFP-treated patients. Preliminary efficacy results are presented in the table. DFP therapy was associated with a significant reduction in the rate of iron accumulation as measured by SF (P<0.0001) (Figure 1), LPI (P<0.001) (Figure 2) and TSAT (P<0.001). LPI ≥ 0.6 µM appeared as early as after 5 transfusions in NC children and was delayed to at least 10 transfusions with DFP therapy. TSAT ≥ 70% appeared after 10 transfusions in NC children and was delayed to at least 17 transfusions with DFP therapy. The results of this study show that LPI and TSAT may reach values ≥ 0.6 µM and ≥ 70%, respectively, after 5 -10 transfusions in children with TM and all NC children had SF ≥ 1000 μg/L after 8-9 transfusions. A sub-therapeutic dose regimen of deferiprone for a mean of 10 months in children with TM and low iron overload was not associated with safety concerns and able to significantly reduce the rate of iron accumulation as measured by SF and the appearance of high levels of LPI and of TSAT. Table Table. Disclosures Berdoukas: ApoPharma Inc: Consultancy. Tricta:ApoPharma Inc: Employment.

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&lt;0.001) and for SF&lt;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&gt; 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 &lt; 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.

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.

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.

Application of Self-Efficacy Theory in Adherence to Iron Chelation Therapy: A Single-Center Cross-Sectional Study

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5284-5284
Author(s):  
Kevin H.M. Kuo ◽  
Richard Ward
Keyword(s):  
Family Support ◽  
Self Efficacy ◽  
Chelation Therapy ◽  
Care Center ◽  
Insurance Coverage ◽  
Iron Chelation ◽  
Comprehensive Care ◽  
Iron Chelation Therapy ◽  
Cross Sectional ◽  
Significant Difference

Abstract 5284 Introduction: Poor adherence to iron chelation therapy (ICT) in beta-Thalassemia Major (TM) is associated with increased risk of cardiac complications and endocrinopathies, and lower survival, with substantial cost to the patient and the health care system. Canada is unique in that several predictors of non-adherence (Financial barriers to medical care, cost of medication and inadequate follow-up) are minimized due to the presence of universal health care, governmental subsidies for medications for patients with chronic disease, and the availability of comprehensive care center for most of the thalassemia patients in the country. Also, the availability of Deferiprone (DFP) via compassionate release program since July 2004 provides an alternative to patients intolerant or having suboptimal response to Deferoxamine (DFO) or Deferasirox (DFX). We hypothesize that the absence of these barriers improve adherence in the Canadian thalassemic population. We also explored self-efficacy as a concept of adherence behavior in our patient population, defined as “individuals' personal beliefs regarding their capabilities to carry out a specific task to achieve a desired outcome” (Bandura, 1989). Methods: A cross-sectional survey was conducted in June and July 2011 at a regional comprehensive care center for transfusion-dependent thalassemia patients. We assessed the age, sex, education, employment status, insurance coverage, types and dosage of ICT, self-reported level of adherence, and side effects. We adapted the Medication Adherence Self-Efficacy Scale (MASES) to assess self-efficacy (Ogedegbe, 2003). Results: Survey return rate was 45% (46/103), with each type of ICT proportionally represented (P = 0.6401). Eight surveys were discarded due to incompletion and 38 were analyzed. Thirty-two patients were on single agent ICT (6 on DFO, 23 on DFX, 3 on DFP) and 6 patients were on combination treatment (1 on DFO+DFX; 3 on DFO+DFP; 2 on DFX+DFP). Median duration of iron chelation was more than 10 years. All patients had either government (n = 10) or workplace (n = 28) coverage. Twenty-three patients (61%) were self-described as completely adherent and 15 were not completely adherent. Mean level of adherence is 90% (SD 16%), similar to those reported in the literature (Trachtenberg et al., 2011), with no significant difference between the different types of ICT (P = 0.1085). Half of the non-adherent patients (8/15, 53%) miss 1 prescribed day of medication per week. There was no significant difference between adherent and non-adherent patients in age (P = 0.1484), sex (P = 0.3764), type of insurance coverage (P = 4752), family support (P = 0.7190), type of ICT (P = 0.0611), participation and satisfaction with the Exjade Patient Support Program (P = 1.000 and 0.3012 respectively), duration of chelation (P = 0.3951), rate of side effects (P = 0.4167), or feelings of depression (P = 0.4780). There was a trend towards differences in education level (P = 0.0565) and a higher proportion of professionals in the non-adherent group. The mean self-efficacy score of patients self-described as completely adherent was significantly higher than the non-completely adherent group (2.66 vs 1.93, P<0.0001). Discussion: In this self-reported survey of patients on ICT in a Canadian regional comprehensive care center, age, presence of family support, and feelings of depression were not found to be a significant predictor of poor adherence, unlike previous studies. This could be because previous studies only examined certain types of ICTs whereas the present study examined all forms of chelation. Small sample sizes of patients on DFO and DFP is the main limitation of the study. This is also the first known application of self-efficacy theory in explaining adherence to ICT. Further studies are required to examine the internal consistency and test-retest reliability of MASES in evaluating self-efficacy in adherence to ICT. Disclosures: Kuo: Novartis Canada: Research Funding. Off Label Use: Deferiprone is an unlicensed drug in Canada and USA. It is an oral iron chelator.

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