scholarly journals Chelator-facilitated removal of iron from transferrin: relevance to combined chelation therapy

2007 ◽  
Vol 409 (2) ◽  
pp. 439-447 ◽  
Author(s):  
Lakshmi D. Devanur ◽  
Robert W. Evans ◽  
Patricia J. Evans ◽  
Robert C. Hider
Keyword(s):  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Removal ◽  
Spectroscopic Methods ◽  
Iron Chelation Therapy ◽  
Simultaneous Presence ◽  
Iron Transfer ◽  
Iron Load ◽  
Combined Administration ◽  
Orally Active

Current iron chelation therapy consists primarily of DFO (desferrioxamine), which has to be administered via intravenous infusion, together with deferiprone and deferasirox, which are orally-active chelators. These chelators, although effective at decreasing the iron load, are associated with a number of side effects. Grady suggested that the combined administration of a smaller bidentate chelator and a larger hexadentate chelator, such as DFO, would result in greater iron removal than either chelator alone [Grady, Bardoukas and Giardina (1998) Blood 92, 16b]. This in turn could lead to a decrease in the chelator dose required. To test this hypothesis, the rate of iron transfer from a range of bidentate HPO (hydroxypyridin-4-one) chelators to DFO was monitored. Spectroscopic methods were utilized to monitor the decrease in the concentration of the Fe–HPO complex. Having established that the shuttling of iron from the bidentate chelator to DFO does occur under clinically relevant concentrations of chelator, studies were undertaken to evaluate whether this mechanism of transfer would apply to iron removal from transferrin. Again, the simultaneous presence of both a bidentate chelator and DFO was found to enhance the rate of iron chelation from transferrin at clinically relevant chelator levels. Deferiprone was found to be particularly effective at ‘shuttling’ iron from transferrin to DFO, probably as a result of its small size and relative low affinity for iron compared with other analogous HPO chelators.

Multiple Packed Red Blood Cell (PRBC) Transfusions In Pediatric Patients With Acute Myeloid Leukemia (AML) Result In a Large Transfusional Iron Dose With The Potential For Long-Term Organ Dysfunction

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2660-2660
Author(s):  
Mohammed Al-Darwish ◽  
Asim F Belgaumi ◽  
Neameh A Farhan ◽  
Ali Al-Ahmari ◽  
Amal Al-Seraihy ◽  
...  
Keyword(s):  
Organ Dysfunction ◽  
Pediatric Patients ◽  
Chelation Therapy ◽  
Iron Chelation ◽  
Left Ventricular Ejection ◽  
Hepatic Iron ◽  
Iron Chelation Therapy ◽  
Body Iron ◽  
Iron Load

Abstract The treatment of AML in children utilizes intensive chemotherapy and often myeloablative hematopoietic cell transplant (HCT). This results in significant myelosuppression, necessitating blood product transfusions. Repeated PRBC transfusions result in an increase in the body iron load which can lead to secondary hemochromatosis and organ dysfunction, particularly the heart and liver. Patients with hemoglobinopathies on chronic PRBC transfusions require iron chelation therapy usually after 10-20 units transfused. While patients with AML receive multiple transfusions, there is little data on the number or volume of PRBC transfused or the estimate of the iron load received. This retrospective study evaluated the number and volumes of PRBC transfusions administered to pediatric (<14 years) patients with AML, and calculated an estimate of the iron infused. Twenty-two patients with AML were diagnosed and treated at our institution between January 2010 and December 2012. There were 13 girls and 9 boys with a median age at diagnosis of 7.5 years (mean 6.95; range 0.4-13.2). One patient died early of sepsis without achieving complete remission (CR), and another died in CR following her last course of chemotherapy. Eight patients underwent HCT following myeloablative conditioning with busulfan, cyclophosphamide and etoposide; the remaining received chemotherapy alone. For patients who completed their chemotherapy the cumulative anthracycline dose was 450 mg/m2. Patients received a median of 17.5 PRBC transfusions (mean 16.6; range 3-28) during the course of their treatment. The cumulative PRBC transfusion volume was 185.4 ml/kg (mean 175.8; range 24.87 – 311.58), which translates to a median iron dose of 129.8 mg/kg (mean 123.1; range 17.4 – 218.1). The median serum ferritin level for those patients who were tested (n=12) was 1794.5 mg/L (mean 9074.5; range 699 – 78500). The median projected hepatic iron content, based on the transfused iron burden was 12.24 mg/g liver dry weight (mean 11.61; range 1.64 – 20.58); 17 (77.3%) patients had projected hepatic iron concentrations in excess of 7.0 mg/g, and none were <1.6 mg/g. Ten patients have developed a > 10 percentage point reduction in their left ventricular ejection fraction (LVEF; range -11% to -45%) however only one patient is on cardiac failure medications. Cardiac T2* MRI studies are being conducted to evaluate cardiac iron status for patients in this cohort. 13 patients were alive in CR at a median follow-up duration of 1.83 years (mean 2.16; range 0.27 – 3.43). Pediatric patients with AML receive large volumes of PRBC transfusions during their treatment and as a consequence accumulate high total body iron. This is in excess of the threshold for chelation therapy, used to prevent organ dysfunction, in patients with hemoglobinopathies. In addition, AML patient also receive significant cardio-toxic medications which may compound the effect of iron on the myocardium. With improvements in long term survival for patients with AML the addition of iron chelation therapy must be studied in order to prevent long term toxicity of AML therapy. Disclosures: No relevant conflicts of interest to declare.

Iron chelation therapy: you gotta have heart

Blood ◽  
2010 ◽  
Vol 115 (12) ◽  
pp. 2333-2334 ◽  
Author(s):  
Alan R. Cohen
Keyword(s):  
Chelation Therapy ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Iron Chelator ◽  
Iron Chelation Therapy ◽  
Cardiac Iron ◽  
Active Iron ◽  
And Function ◽  
Orally Active

The study by Pennell et al in this issue of Blood reports the effect of the orally active iron chelator deferasirox on cardiac iron and function in patients with thalassemia major.

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.

Overview of Iron Chelation Therapy with Desferrioxamine and Deferiprone

Hemoglobin ◽  
2009 ◽  
Vol 33 (sup1) ◽  
pp. S58-S69 ◽  
Author(s):  
Maria D. Cappellini ◽  
Khaled M. Musallam ◽  
Ali T. Taher
Keyword(s):  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelation Therapy

THE MANAGEMENT OF IRON CHELATION THERAPY

2008 ◽  
Vol 54 (4) ◽  
pp. 503-507
Author(s):  
M. J. Pippard ◽  
S. T. Callender
Keyword(s):  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelation Therapy

Iron chelation therapy to prevent the manifestations of aceruloplasminemia

Neurology ◽  
2015 ◽  
Vol 85 (12) ◽  
pp. 1085-1086 ◽  
Author(s):  
Francesco Bove ◽  
Alfonso Fasano
Keyword(s):  
Chelation Therapy ◽  
Iron Chelation ◽  
Iron Chelation Therapy
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