Assessing Compliance to Iron Chelation Therapy in Patients with Thalassemia.

Abstract Introduction: Compliance with Desferrioxamine is the most important factor determining morbidity and mortality in transfusion dependent thalassemia patients. Clinical and laboratory methods to assess compliance are essential in modifying patient treatment and determining efficacy of therapy. Simple screening tools for patient compliance assessment needs to be developed and must be correlated with reliable measurement of iron stores. Objective: The purpose of this study is to assess a simple compliance tool and compare it with quantitative iron stores. Methods and Patients: A Likert Numerical Scale assessed Adherence to a chelation program. This scale rated adherence to compliance from 1 (poor) to 5 (excellent). 90 transfusion dependent thalassemia patients underwent a brief interview, followed by the administration of the Likert Numerical scale to both the patient and their corresponding physician. This was followed by quantitation of their Serum Ferritin (SF) and liver iron concentration (LIC) utilizing the LTc- SQUID biosusceptometer (Ferritometer ®, Model 5700, Tristan Technologies, San Diego, USA). A subset of patients was followed serially to determine if compliance and liver iron changed as a result of the initial testing. Results: LIC was assessed in a total of 90 transfusion-dependent patients with a mean age of 17 years (4 – 48 y). The average duration of transfusion and chelation therapy was 14.6 y (range: 1 – 42) and 12.1 y (1 – 40 yrs), respectively. The median value for LIC was 2307 μg/g-liver (range: 364 – 7570). 78 % of patients rated themselves as very compliant (4 or 5) yet 40% of these patients had elevated LIC > 2500μg/g-liver. 92% of the patients received an identical rating from their physician (Spearman rank RS = 0.9). 19/28 patients with high compliance ratings had elevated LIC (> 2500 μg/g) secondary to recent onset of chelation therapy or inadequate Desferrioxamine dosing when compared to their PRBC cc/kg/y requirements. In 9 compliant patients, no apparent explanation for their elevated liver iron could be found. A subgroup of 16 patients with a mean age of 17 years (3 – 44y) underwent serial LIC and SF measurements. The median interval between first and last measurements was 10 month (range: 4–15). At the time of first SQUID measurement, the median values for LIC and SF were1202 μg/g-liv (893–6167) and 1502 μg/l (660–4496) respectively. Following counseling concerning the liver iron results, DFO dose changes occurred and compliance rose from 1 (poorest) to 5 (excellent) in 7/8 patients studied. The LIC decreased by 25% (7–60%) as the compliance rate improved. In contrast, the SF fluctuated, but at the time of study testing, 10 patients had a significant increase in serum ferritin despite a lower LIC. Conclusion: Patient compliance can be adequately assessed and result in improved iron balance. However, SF may underestimate compliance and result in inadequate management. We recommend all patients undergo serial assessment of compliance accompanied with LIC and necessary counseling containing their iron stores.

Download Full-text

Effect of transfusional iron intake on response to chelation therapy in β-thalassemia major

Blood ◽

10.1182/blood-2007-08-109306 ◽

2008 ◽

Vol 111 (2) ◽

pp. 583-587 ◽

Cited By ~ 103

Author(s):

Alan R. Cohen ◽

Ekkehard Glimm ◽

John B. Porter

Keyword(s):

Chelation Therapy ◽

Iron Concentration ◽

Chelating Agent ◽

Thalassemia Major ◽

Phase Iii ◽

Iron Loading ◽

Iron Intake ◽

Liver Iron ◽

Iron Stores ◽

Using Data

The success of chelation therapy in controlling iron overload in patients with thalassemia major is highly variable and may partly depend on the rate of transfusional iron loading. Using data from the 1-year phase III study of deferasirox, including volumes of transfused red blood cells and changes in liver iron concentration (LIC) in 541 patients, the effect of iron loading on achieving neutral or negative iron balance was assessed in patients receiving different doses of deferasirox and the comparator deferoxamine. After dose adjustment, reductions in LIC after 1 year of deferasirox or deferoxamine therapy correlated with transfusional iron intake. At a deferasirox dose of 20 mg/kg per day, neutral or negative iron balance was achieved in 46% and 75% of patients with the highest and lowest transfusional iron intake, respectively; 30 mg/kg per day produced successful control of iron stores in 96% of patients with a low rate of transfusional iron intake. Splenectomized patients had lower transfusional iron intake and greater reductions in iron stores than patients with intact spleens. Transfusional iron intake should be monitored on an ongoing basis in thalassemia major patients, and the rate of transfusional iron loading should be considered when choosing the appropriate dose of an iron-chelating agent. This study is registered at http://clinicaltrials.gov as NCT00061750.

Download Full-text

Insights into Relationships Between Serum Ferritin and Liver Iron Concentration Trends during 12 Months of Iron Chelation Therapy with Deferasirox – a Post-Hoc Analysis from the Epic Study

Blood ◽

10.1182/blood.v124.21.52.52 ◽

2014 ◽

Vol 124 (21) ◽

pp. 52-52 ◽

Cited By ~ 2

Author(s):

John B Porter ◽

Mohsen Elalfy ◽

Ali T Taher ◽

Lee Lee Chan ◽

Szu-Hee Lee ◽

...

Keyword(s):

Board Of Directors ◽

Serum Ferritin ◽

Research Funding ◽

Chelation Therapy ◽

Iron Concentration ◽

Iron Intake ◽

Advisory Committees ◽

Liver Iron ◽

Baseline Serum ◽

Post Hoc

Abstract Background Serum ferritin is regularly used to assess response to chelation therapy and correlates significantly with liver iron concentration (LIC) particularly when LIC is <7 mg Fe/g dry weight (dw) and serum ferritin is <4000 ng/mL. The absence of a serum ferritin decrease in the first months of a new chelation regime may be interpreted as a lack of response with respect to decreasing body iron load. However, sequential LIC determination (where available) has indicated that many of these patients do indeed have a decrease in LIC. This clinical experience requires greater understanding, particularly the nature of the LIC and serum ferritin relationship at baseline serum ferritin values ≥4000 ng/mL. The aim of this post-hoc analysis of the EPIC study was to gain insight into the relationship between serum ferritin and LIC in response to deferasirox over 1 year, in a large patient cohort, so that serum ferritin trends can be more clearly interpreted and evidence-based practical guidance be given for patients with transfusion-dependent thalassemia (TDT). Methods TDT patients were recruited from 25 sites, received 1-year of deferasirox treatment and had serum ferritin and R2 magnetic resonance imaging (R2-MRI)-assessed LIC measurements at baseline and 1 year. Summary statistics are provided for serum ferritin and LIC responders (decrease, any change from baseline <0) and nonresponders (increase or no change, any change from baseline ≥0), and for baseline serum ferritin categories (≥4000 vs <4000 ng/mL). Results Of the 374 patients analyzed in the EPIC liver MRI substudy, 317 had TDT, of which 72.7% (n=226) had a serum ferritin response and 27.3% (n=85) had no response. Importantly, after 1 year LIC decreased in approximately half of serum ferritin nonresponders (51.8%; n=44; Table) and in 79.6% of serum ferritin responders (n=180). Median (min, Q1, Q3, max) change in LIC (mg Fe/g dw) was –5.4 (–38.5, –11.7, –0.9, 15.4) in serum ferritin responders and –0.2 (–18.4, –2.6, 2.7, 19.6) in nonresponders. Median (range) transfusional iron intake (mg/kg/day) was similar in serum ferritin responders (0.30 [0.01–1.49]) and nonresponders (0.37 [0.02–1.00]). Median deferasirox dose (mg/kg/day) was higher in serum ferritin responders than nonresponders (28.1 [9.8–40.4] vs 23.7 [9.7–37.9]). Evaluation of responses by baseline serum ferritin showed that a greater proportion of serum ferritin responders with baseline serum ferritin <4000 ng/mL also had decreased LIC (88.7% [n=102]; Table), compared with serum ferritin responders with baseline serum ferritin ≥4000 ng/mL (70.3% [n=78]). However, serum ferritin baseline category had no effect on the proportion of patients who decreased LIC despite having no serum ferritin response (52.6% [n=30], <4000 ng/mL; 50.0% [n=14], ≥4000 ng/mL; Table). There was little change in median LIC in serum ferritin nonresponders after 1 year regardless of baseline serum ferritin value (–0.3 [–13.5–18.7] for <4000 ng/mL and 0.2 [–18.4–19.6] for ≥4000 ng/mL). Assessment by change in serum ferritin and LIC quadrants indicated that patients without serum ferritin or LIC response had the lowest baseline median (range) serum ferritin and LIC (2155 [480–9725] ng/mL; 11.9 [1.8–37.5] mg Fe/g dw; n=41), and received a lower median deferasirox dose (23.7 [9.7–36.0] mg/kg/day). Overall, median LIC decrease (mg Fe/g dw) was smaller in patients with baseline serum ferritin <4000 ng/mL (n=172) than in those with serum ferritin ≥4000 ng/mL (–2.8 [–38.5–18.7] vs –4.9 [–31.1–19.6]; n=139). Median iron intake was similar between groups. Discussion and conclusions A decrease in LIC was seen in ~80% of serum ferritin responders after 1 year of deferasirox; a greater proportion of serum ferritin responders (88%) decreased LIC when baseline serum ferritin was <4000 ng/mL. Importantly, among patients with no serum ferritin response up to half may be responding with respect to iron balance, indicating that a lack of serum ferritin response should be interpreted with caution. However, since a decrease in serum ferritin predicts a decrease in LIC in 80% of patients, MRI measurement (where available) should be prioritized for patients with serum ferritin increase/no change. Overall, serum ferritin response can help predict LIC response, but in some patients treated with deferasirox, serum ferritin may not accurately reflect removal of iron from the body. Figure 1 Figure 1. Disclosures Porter: Novartis: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria; Celgene: Consultancy; Cerus: Membership on an entity's Board of Directors or advisory committees; Alnylam: Membership on an entity's Board of Directors or advisory committees. Taher:Novartis: Honoraria, Research Funding. Sutcharitchan:Novartis: Research Funding. Aydinok:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Chakravarty:Novartis: Employment. El-Ali:Novartis: Employment.

Download Full-text

Imaging of Body Iron Stores in Transfusion-Dependent Patients By Liver Dual- Energy CT

Blood ◽

10.1182/blood.v124.21.2677.2677 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2677-2677

Author(s):

Hironori Kobayashi ◽

Norihiko Yoshimura ◽

Takashi Ushiki ◽

Yasuhiko Shibasaki ◽

Masato Moriyama ◽

...

Keyword(s):

Blood Cell ◽

Serum Ferritin ◽

Red Blood Cell ◽

Chelation Therapy ◽

Iron Chelation ◽

Iron Deposition ◽

Liver Iron ◽

Body Iron ◽

Iron Stores ◽

Red Blood Cell Transfusions

Abstract [Background] Chronic red blood cell transfusions, leading to iron overload, cause hepatic, cardiac, and endocrine dysfunction. It is very important to monitor body iron stores and to start optimal iron chelation therapy. Serum ferritin, which is widely used as a surrogate marker of body iron stores, elevate under inflammation or liver injury. Therefore, reliable techniques to evaluate body iron stores are needed. The liver iron concentration (LIC) is thought to be an indicator of total body iron stores and measurement of the T2* value by MRI has been a standard noninvasive technique to evaluate LIC. It should be worthwhile using CT, which is lower cost and widely applied in clinical setting. Dual-energy CT (DECT) is a technique to obtain additional information regarding tissue composition compared with what single-energy CT can provide. This technique is based on the fact that substances show different densities by two different energies. However, the role of DECT in monitoring LIC remains to be clarified. We examined whether a DECT could be a new technique for the measurement of LIC. [Patients and Methods] Eight transfusion-dependent patients underwent DECT. Patient 1 was a 54-year-old male with MDS (RCMD-RS). He received 66 U red blood cell transfusions in our hospital, and depended on transfusion in another hospital, but the total doses were not available. Patient 2 was a 37-year-old male with AML in 2nd relapse. His total red blood cell transfusions were 54 U. Patient 3 was a 66-year-old female with AML with MRC in 1st CR. She received 37 U red blood cell transfusions in our hospital, and depended on transfusion in another hospital, but total doses were not available. Patient 4 was a 47-year-old female who had received renal transplantation for chronic renal failure. She received 12 U red blood cell transfusions in our hospital, and had a long history of transfusion dependence in another hospital, but total doses were not available. Patient 5 was a 57-year-old male with MDS (RCMD). His total red blood cell transfusions were 148 U, and he received iron chelation therapy. Patient 6 was a 65-year-old male with AML with MRC. His total red blood cell transfusions were 82 U, and he received iron chelation therapy. Patient 7 was a 47-year-old male with AML in 3rd CR. He received 28 U red blood cell transfusions in our hospital, and depended on transfusion in another hospital, but total doses were not available. Patient 8 was a 52-year-old female with AA. Her total blood cell transfusions were 92 U. [Results] All patients were examined for serum ferritin and patients 1, 3, 4, 6, 7, and 8 also underwent liver MRI. Serum ferritin levels of patients 1, 3, 4, 6, 7, and 8 were 961, 2168, 7875, 795, 1921, and 5104 ng/ml, respectively. These patients showed hypointensity on MRI T2*-weighted images, and also showed liver iron deposition by DECT. Serum ferritin of patient 5 was 4042 ng/ml, and he showed liver iron deposition by DECT. Serum ferritin of patient 2 was 6113 ng/ml, and he did not show liver iron deposition by DECT. [Conclusion] Our results suggest that liver DECT could visualize liver iron deposition of transfusion-dependent patients and could be a new technique for the measurement of LIC instead of MRI. Disclosures No relevant conflicts of interest to declare.

Download Full-text

The Association Between Iron Over Load and Tanner Stage Retardation in the Females with B-Thalassemia Major

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i1.1856 ◽

2020 ◽

Vol 11 (1) ◽

pp. 546-552

Author(s):

Suzan Sabbar Mutlag

Keyword(s):

Serum Ferritin ◽

Iron Concentration ◽

Growth Failure ◽

Iron Chelation ◽

Tanner Stage ◽

Thalassemia Major ◽

The Body ◽

Liver Iron ◽

Iron Stores ◽

Female Patients

Despite optimal therapy of patients with B- major thalassemia included repeated transfusion of blood program and iron chelation agents helped by increasing survival of these patients but remained a major problem in adolescents of these patients such as growth failure and hypogonadism. This study was aimed to determine the relationship between iron overload and tanner stage retardation among female patients with B- major thalassemia in Thalassemia Hospital in Diwaniyah Governorate. The current study occurred on all female patients diagnosed β-thalassemia major depends on the blood tests, with their age range from 13years to 16 years who registered in Thalassemia unit in Al- Diwaniyah Governorate, Republic of Iraq. In the physical examination, the patients were assessed for weight, height, Tanner stages, and body mass index(BMI), which recorded. S. Ferritin value was used to assess the iron load, and pelvic ultrasound was checked to assess the size of the uterus and both ovaries. The results of the currents study revealed that the total numbers of B- thalassemia major female patients are 31 patients, aged 13-16 years. Age of patients at which diagnosed of B- major thalassemia range from 0.17 to 5 year. The frequency of Blood transfusion (time/Year) ranges from 6 to 33 times/Year. The level of serum ferritin of the patients was ranged from 913-12000 ng/ml with. Tanner stage I was predominant, accounting for 87%, whereas stage II and III accounted for 10% and 3%, respectively. There was a significant negative relation between times transfusion of blood and Tanner. There was a significant correlation between Uterus size, ovarian size, and Tanner stage. Because of inflammation falsely increase serum ferritin or due to the relation between body iron in the body and level of serum ferritin is not always within the linear range, especially in the condition of inflammation or tissue damage. So that level of serum ferritin is not an adequate measure of iron stores in patients with major thalassemia. Therefore, we needed another indicator to measure iron stores in patients with thalassemia major such as liver iron concentration.

Download Full-text

Serum Ferritin a Predictor of Iron Overload in Patients with Thalassemia and Sickle Cell Disease?.

Blood ◽

10.1182/blood.v104.11.3789.3789 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3789-3789 ◽

Cited By ~ 1

Author(s):

Zahra Pakbaz ◽

Roland Fischer ◽

Richard Gamino ◽

Ellen B. Fung ◽

Paul Harmatz ◽

...

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Sickle Cell ◽

Serum Ferritin ◽

Iron Concentration ◽

Cell Disease ◽

Liver Iron Concentration ◽

Liver Iron ◽

Iron Stores ◽

Significant Difference

Abstract Introduction: Monitoring iron overload by serum ferritin in patients with hemosiderosis is still a routine practice although its limitations are widely studied and well known. Using non-invasive liver iron assessment by quantitative MRI or by biomagnetic liver susceptometry (BLS) with SQUID biomagnetometers would be the better alternative, however, these methods are available at only a few centers worldwide. Objective: To determine the relationship between serum ferritin (SF) and liver iron concentration (LIC), measured by BLS at CHRCO, in patients with different types of hemosiderosis. Methods and Patients: A total of 97 patients with thalassemia (TM: 3 to 52 y, 54% females) and 39 patients with sickle cell disease (SCD: 5 to 49 y, 60% female) were prospectively assessed for LIC and SF. Both tests were performed within 2 weeks of each other. Most patients with TM and SCD were chronically transfused, while 10 b-thalassemia intermedia (TI), 5 HbE/β-thalassemia (HbE), and 5 SCD patients were not on transfusion programs. LIC was measured by LTc SQUID biosusceptometer system (Ferritometer®, Model 5700, Tristan Technologies, San Diego, USA) under the standardized Hamburg-Torino-Oakland protocol. A non-parametric test (U-test) was utilized to analyze differences between SF and LIC data. Results: In chronically transfused TM and SCD patients, the median SF and LIC were very similar (Table I). In TI&HbE patients, ferritin results were disproportionately low with respect to LIC. In order to improve prediction of iron stores by SF, the SF/LIC ratio was calculated. There was a significant difference between the median ratios of the two groups of transfused and non- transfused thalassemia patients, 0.82 vs. 0.32 [μg/l]/[μg/gliver], respectively (p < 0.01). In SCD patients the ratio is significantly (p < 0.01) higher. Conclusion: Present data confirm ferritin to be a poor predictor of liver iron stores both in sickle cell disease and thalassemia. Relying only on ferritin to monitor iron overload in patients with hemosiderosis can be misleading, especially, in sickle cell disease and non-transfused thalassemia patients. Taking into account disease specific ferritin-LIC relations, could improve the prediction of iron stores. However, assessment of liver iron stores is the ultimate method to initiate and adjust chelation treatment in order to avoid progressive organ injury. Table I. Median values and ranges ( − ) of serum ferritin (SF) and liver iron concentration (LIC) in transfused (Tx) and non-transfused (non-Tx) hemosiderosis patients. Patient group n SF μg/l] LIC [mg/gliver ] SF:LIC Thalassemia Tx 82 1721 (209–8867) 3424 (364–7570) 0.82 (0.3–1.8) TI &HbE non-Tx 15 766 (52–2681) 2174 (226–5498) 0.32 (0.1–1.4) SCD Tx 34 2757 (400–9138) 1941 (518–6670) 1.2 (0.6–3.3)

Download Full-text

JADENU® SUBSTITUTING EXJADE® IN IRON OVERLOADED Β- THALASSEMIA MAJOR (BTM) PATIENTS: A PRELIMINARY REPORT OF THE EFFECTS ON THE TOLERABILITY, SERUM FERRITIN LEVEL, LIVER IRON CONCENTRATION AND BIOCHEMICAL PROFILES

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2018.064 ◽

2018 ◽

Vol 10 ◽

pp. e2018064 ◽

Cited By ~ 1

Author(s):

Vincenzo De Sanctis

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Serum Ferritin Level ◽

Chelation Therapy ◽

Ferritin Level ◽

Iron Concentration ◽

Liver Iron Concentration ◽

Liver Iron ◽

Transfusion Therapy ◽

Biochemical Profiles

Abstract. Introduction: Due to the chronic nature of chelation therapy and the adverse consequences of iron overload, patient adherence to therapy is an important issue. Jadenu ® is a new oral formulation of deferasirox (Exjade ®) tablets for oral suspension. While Exjade® is a dispersible tablet that must be mixed in liquid and taken on an empty stomach, Jadenu ® can be taken in a single step, with or without a light meal, simplifying administration for the treatment of patients with chronic iron overload. This may significantly improve the compliance to treatment of patients withβ-thalasemia major (BMT). The aim of this study was to evalute the drug tolerability and the effects of chelation therapy on serum ferritin concentration, liver iron concentration (LIC) and biochemical profiles in patients with BMT and iron overload. Patients and Methods: Twelve selected adult patients BMT (mean age: 29 years; range:15-34 years) were enrolled in the study. All patients were on monthly regular packed cell transfusion therapy to keep their pre-transfusional hemoglobin (Hb) level not less than 9 g/dL. They were on Exjade ® therapy (30 mg/kg per day) for 2 years or more before starting Jadenu ® therapy (14-28 mg/kg/day). The reason for shifting from Deferasirox ® to Jadenu ® therapy was lack of tolerability, since most of the patients described Deferasirox ® as not palatable. Lab investigations included montly urine analysis and measurement of their serum concentrations of creatinine, fasting blood glucose (FBG), serum ferritin, alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transferase (AST) and albumin concentrations. LIC was measured using FerriScan ®. Thyroid function, vitamin D and serum parathormone, before and one year after starting Jadenu ® therapy, were also assessed. Results: Apart from some minor gastrointestinal complaints reported in 3 BMT patients that did not require discontinuation of therapy, other side effects were not registered during the treatment. Subjectively, patients reported an improvement in the palatability of Jadenu® compared to Exjade ® therapy in 8 out of 12 BMT patients. A non-significant decrease in LIC and serum ferritin levels was observed after 1 year of treatment with Jadenu ® . A positive significant correlation was found between serum ferritin level and LIC measured by FerriScan ® method. LIC and serum ferritin level correlated significantly with ALT level (r = 0.31 and 0.45 respectively, p < 0.05). No significant correlation was detected between LIC and other biochemical or hormonal parameters. Conclusion: Our study shows that short-term treatment with Jadenu ® is safe but is associated with a non-significant decrease in LIC and serum ferritin levels. Therefore, there is an urgent need for adequately-powered and high-quality trials to assess the clinical efficacy and the long-term outcomes of new deferasirox formulation.

Download Full-text

Iron Chelation Therapy with Deferasirox (Exjade®, ICL670) or Deferoxamine Is Effective in Reducing Iron Overload in Patients with Advanced Fibrosis and Cirrhosis.

Blood ◽

10.1182/blood.v106.11.2696.2696 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2696-2696 ◽

Cited By ~ 2

Author(s):

E. Angelucci ◽

B. Turlin ◽

D. Canatan ◽

A. Mangiagli ◽

V. De Sanctis ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Chelation Therapy ◽

Iron Concentration ◽

Iron Chelation ◽

Iron Chelator ◽

Advanced Fibrosis ◽

Liver Iron ◽

Once Daily ◽

Tissue Iron

Abstract Introduction: Although the direct measurement of iron from a liver biopsy is the reference standard method to determine liver iron concentration (LIC), results are highly unreliable in patients with advanced fibrosis and cirrhosis. As a result, chelation therapy is difficult to monitor in this patient population where effective chelation therapy may be critical. It is therefore important to assess parameters additional to LIC in order to accurately assess body iron in these patients. Aim: To analyze the efficacy of chelation with deferoxamine (DFO) and the investigational once-daily, oral iron chelator deferasirox (DSX) in patients with advanced fibrosis participating in DSX registration studies. Methods: A subgroup of patients from DSX Studies 0107 and 0108 were selected based on a staging result according to the Ischak scale of 5 (incomplete cirrhosis) or 6 (probable or definite cirrhosis), measured either at baseline or after 1 year of chelation therapy. The subgroup of patients with β-thalassemia participating in Study 0107 received DSX (n=26) or DFO (n=30). In Study 0108, the subgroup of patients with β-thalassemia unable to be treated with DFO (n=12) or patients with anemias other than β-thalassemia (n=7) were treated with DSX only. In both studies, patients received chelation therapy according to baseline LIC. Results: In Study 0107, treatment with DSX or DFO led to a decrease in semi-quantitative tissue iron score (TIS) and LIC, which were paralleled by changes in serum ferritin. TIS, LIC and serum ferritin in a subgroup of patients with advanced fibrosis and cirrhosis treated with DSX and DFO (Study 0107) TIS LIC, mg Fe/g dw Serum ferritin, ng/mL DSX (n=26) DFO (n=30) DSX (n=26) DFO (n=30) DSX (n=26) DFO (n=30) *Median (min, max) Baseline* 35.5 (4,39) 34 (10,52) 25.5 (2.4,45.9) 19.5 (3.9,55.1) 4195 (321,12646) 4144 (653,15283) Change from baseline* −2 (−43,20) −2 (−25,16) −9.4 (−42.2,13.1) −3.1 (−24.5,12.4) −1269 (−7082,3609) −951 (−8259,1264 Similarly, in Study 0108, DSX treatment produced a decrease in all 3 parameters in patients with β-thalassemia or rare anemia. TIS, LIC and serum ferritin in a subgroup of β-thalassemia and rare anemia patients with advanced fibrosis and cirrhosis (Study 0108) TIS LIC, mg Fe/g dw Serum ferritin, ng/mL β-thalassemia (n=12) Rare anemia (n=7) β-thalassemia (n=12) Rare anemia (n=7) -thalassemia β (n=12) Rare anemia (n=7) *Median (min, max) Baseline* 35 (4,48) 41 (32,49) 29.4 (3.8,37.4) 26.3 (15,51.3) 4813 (440,11698) 2385 (1553,9099) Change from baseline* 2 (−19,27) −3 (−20,1) −1.6 (−18,9.9) −10 (−13.9,8.8) −986 (−4453,2131) −1322 (−2609,1901) Conclusions: Chelation therapy with DSX or DFO is effective in reducing iron overload in patients with advanced fibrosis and cirrhosis. The trends observed in TIS and LIC were closely mirrored by changes in serum ferritin, highlighting the validity of this method for monitoring chelation therapy in this population.

Download Full-text

Serum Ferritin and Liver Iron Concentration in Patients with Iron Overload.

Blood ◽

10.1182/blood.v106.11.3833.3833 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3833-3833

Author(s):

Zahra Pakbaz ◽

Roland Fischer ◽

Ellen Fung ◽

Peter Nielsen ◽

Rainer Engelhardt ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Chelation Therapy ◽

Iron Concentration ◽

Liver Iron Concentration ◽

Liver Iron ◽

Transfusion Therapy ◽

Poor Predictor ◽

The Individual ◽

The Relationship

Abstract Despite its limitations, serum ferritin (SF) is commonly used to monitor chelation therapy in primary and secondary hemochromatosis. To better predict liver iron concentration (LIC), we prospectively investigated the relationship between SF and LIC in a total of 421 patients with primary (HFE-1 associated, n=241) or secondary hemochromatosis (n=180), consisting of chronically transfused thalassemia (Tx-Thal: n=89) or sickle cell disease patients (Tx-SCD: n=45) and transfusion independent thalassemia patients (nTx-Thal: n=26). In all patients, LIC was measured by SQUID biosusceptometry. SF correlated with LIC (RS = 0.51–0.83, p < 0.001) but was a poor predictor for LIC. SF was significantly lower (p < 0.001) in nTx-Thal and HFE-1 patients despite similar LIC (421 – 5524 μg/g-liver) and it was higher in Tx-SCD compared to Tx-Thal (p = 0.03). In order to improve the value of SF, we calculated the SF/LIC ratio for each group. SF/LIC remained stable over time in patients whose therapy did not change. In iron loaded patients without blood transfusion therapy (nTx-Thal and HFE-1), the median SF/LIC ratio was significant lower (0.32 and 0.43) as compared to transfused patients (Tx-Thal: 0.87, HCV-Thal: 0.99, Tx-SCD: 1.2), probably, indicating differences in the secretion of ferritin into plasma. We conclude that SF alone can mislead the iron unloading therapy as it underestimates LIC in nTx-Thal patients and overestimates LIC in Tx-SCD patients. Once the initial LIC value is obtained and the individual SF/LIC ratio is determined in a patient, the ratio together with SF may be more useful than SF alone to monitor iron overload and predict LIC.

Download Full-text

Iron Chelation Therapy with Deferasirox (Exjade®, ICL670) or Deferoxamine Results in Reduced Hepatocellular Inflammation and Improved Liver Function in Patients with Transfusion-Dependent Anemia.

Blood ◽

10.1182/blood.v106.11.823.823 ◽

2005 ◽

Vol 106 (11) ◽

pp. 823-823 ◽

Cited By ~ 6

Author(s):

P. Brissot ◽

B. Turlin ◽

G.L. Forni ◽

G. Alimena ◽

G. Quarta ◽

...

Keyword(s):

Liver Function ◽

Liver Biopsy ◽

Serum Ferritin ◽

Liver Tissue ◽

Chelation Therapy ◽

Iron Concentration ◽

Iron Chelation ◽

Iron Chelation Therapy ◽

Hepatocellular Injury ◽

Liver Iron

Abstract Transfusional hemosiderosis is often associated with hepatic siderosis or infection with hepatotropic viruses, resulting in hepatocellular injury and progression to chronic liver disease. Liver biopsy is the method of choice for directly assessing damage; scales have been developed to measure necroinflammatory activity (grading) and tissue fibrosis (staging). Iron chelation therapy is historically known to decrease morbidity associated with hepatosiderosis. Aim: To assess 1 year’s chelation therapy with the novel once-daily oral chelator, deferasirox (DSX), or the current standard deferoxamine (DFO), on pathology of liver tissue in chronically transfused patients. Methods: Liver biopsy was performed at baseline and after 1 year in patients participating in DSX Studies 0107 (n=454) and 0108 (n=101). All patients, except 25 in 0107 and 3 in 0108, had liver tissue evaluated by pathology. In 0107, patients with β-thalassemia were randomized to DSX (5, 10, 20 or 30 mg/kg/day; n=224) or DFO (<25, 25–35, 35–50 and ≥ 50 mg/kg; n=230) according to baseline liver iron concentration (LIC). In 0108, patients with β-thalassemia unable to be treated with DFO (n=61) and patients with rare anemias (MDS, DBA and others) (n=40) were enrolled and received DSX only. Grading and staging were determined from biopsy by the Ishak method; LIC was measured in parallel by atomic absorption spectrometry. Results: DSX and DFO dose-dependently affected grading, which mirrored effects on LIC and serum ferritin. DSX 5 and 10 mg/kg increased these parameters, while stabilization and decreases were seen with the highest doses of both chelators, regardless of hepatitis C status. In 0107, a decrease in mean ±SD necroinflammatory score was noted with DSX 30 mg/kg (2.5 ±1.6 to 1.7 ±1.3, n=95) and DFO ≥ 50 mg/kg 5 days/week (2.1 ±1.6 to 1.4 ±1.3, n=95). Similar results were observed in 0108 for β-thalassemia (2.4 ±1.7 to 1.7 ±1.6, n=58) and rare anemia patients (1.8 ±1.5 to 1.5 ±1.3, n=40). This decrease was accompanied by dose-dependent modification of available liver enzyme levels in 0107 (Table); with a similar trend in 0108. No obvious modification of staging was observed after 1 year of treatment, suggesting that longer time periods are needed to observe potential reversal of fibrosis. Change in liver enzymes (ALT; U/L) by treatment (Study 0107) DSX, mg/kg DFO, mg/kg 5 10 20 30 <25 25–35 35–50 ≥ 50 n=8 n=43 n=64 n=107 n=6 n=28 n=88 n=107 Mean ± SD 34.9 21.9 3.6 −2.8 −13.9 −3.7 −2.8 −12.4 ±35.1 ±25.2 ±28.7 ±79.3 ±29.7 ±17.6 ±20.7 ±38.6 Median (range) 36.8 10.0 0.5 −8.0 −10.8 −1.8 −0.8 −9.5 (−19.0, 101.5) (−7.5, 105.0) (−111.5, 91.0) (−143.0, 711.0) (−61.0, 27.0) (−55.5, 32.0) (−93.5, 70.5) (−171.0, 193.3) Conclusions: Although the data show considerable variability, results suggest that chelation therapy with DSX or DFO is associated with reduced hepatocellular inflammation and improved liver function. These modifications appear to be linked with effects on LIC and serum ferritin levels.

Download Full-text