Correlation between Dose-Dependent Reductions in Serum Transaminase (ALT) and Serum Ferritin Levels during Long-Term Chelation Therapy with Deferasirox (Exjade®, ICL670).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3817-3817 ◽  
Author(s):  
P. Brissot ◽  
Y. Deugnier ◽  
P. Cianciulli ◽  
H. Cario ◽  
M. Jeng ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Dose Escalation ◽  
Clinical Studies ◽  
Patient Population ◽  
Serum Transaminase ◽  
Liver Iron ◽  
Transfusion Therapy ◽  
The Core ◽  
Number Of Patients

Abstract Introduction: Hepatic siderosis, a result of chronic transfusion therapy, leads to hepatocellular injury and progression to chronic liver disease. Increases in serum transaminase levels are indicative of progressive liver damage. The effect of deferasirox (Exjade®, ICL670), a novel, once-daily oral chelator, on liver iron content and pathology in chronically transfused patients has been assessed in Phase II and III clinical studies. A sub-analysis of pooled data from the planned 4-year extension of two pivotal studies sought to correlate the long-term changes in serum ALT levels with those of serum ferritin in iron-overloaded patients during treatment with deferasirox. Methods: In these two clinical studies, 480 patients with β-thalassemia (β-thal), myelodysplastic syndromes (MDS), Diamond-Blackfan anemia (DBA), and other transfusion-dependent anemias received deferasirox at 5, 10, 20 or 30 mg/kg/day according to baseline liver iron concentrations for 12 months. In the extension phases, doses were titrated according to patient response, with dose escalation for patients who did not receive sufficient drug in the core study to reduce iron burden. Serum ferritin and ALT levels were assessed at baseline and monthly during the core and extension phases. For this analysis, serum ferritin and ALT levels were analyzed in the combined patient groups who received deferasirox 5 and 10 mg/kg/day, and in those who received 20 and 30 mg/kg/day. Results: Throughout the entire period, deferasirox at 20 and 30 mg/kg/day resulted in a negative iron balance in transfused patients with secondary iron overload. Changes from baseline to week 128 (2.5 years) for serum ferritin and ALT levels are presented. The figure shows that deferasirox at 20 and 30 mg/kg/day decreased median serum ferritin. These decreases were mirrored by decreases in ALT, with a Spearman’s rank-correlation 0.67. Patient numbers shown are baseline/week 128. A number of patients had not reached week 128 of treatment at the time of data cut-off. Figure Figure Decreases in ALT were also observed after dose escalation in the extension phase in patients originally assigned deferasirox 5 and 10 mg/kg/day. There were no consistent relevant changes in other biochemical liver parameters, such as serum aspartate transaminase, in this patient population. Conclusions: With long-term follow-up of this large patient population, correlation between decreases in serum ferritin and ALT levels was high, indicating an association between iron burden and liver dysfunction, and further emphasizing the potential beneficial effect of deferasirox on hepatic function.

Long-Term Effects of Deferasirox (Exjade®, ICL670) on Serum Ferritin: Outcome of Dose Adjustments in Achieving Maintenance or Reduction in Body Iron Stores.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1769-1769 ◽  
Author(s):  
J.B. Porter ◽  
A. Cohen ◽  
L. Agaoglu ◽  
A. Ganser ◽  
M.D. Cappellini ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Iron Concentration ◽  
Extension Phase ◽  
Long Term Effects ◽  
Liver Iron ◽  
Body Iron ◽  
The Core ◽  
Core Phase ◽  
The Impact

Abstract During 1-year core phases of two deferasirox trials, doses were initially assigned by baseline liver iron concentration (LIC). In these regularly transfused patients (mean iron intake 0.37 mg/kg/day), a clear dose response was observed: deferasirox 20/30 mg/kg/day effectively maintained/reduced body iron, 10 mg/kg/day maintained body iron in patients with low transfusion rates, whereas 5 mg/kg/day removed less iron than added by ongoing transfusions. This post-hoc analysis evaluates the impact on serum ferritin (SF) of dose increases during the extension phases, in patients who initially received 5/10 mg/kg/day. In patients who initially received deferasirox 5/10 mg/kg/day with increasing iron burden, doses were generally increased to 20–30 mg/kg/day during the first 6 months of the extension phase. Dose modifications for patients on 20/30 mg/kg/day were based on safety and efficacy parameters. SF was measured monthly. 480 patients (β-thalassemia, n=381; myelodysplastic syndromes, n=47; other anemias, n=52) initially received deferasirox 5/10 (n=119), 20 (n=136) or 30 (n=225) mg/kg/day in the core phase. Most continued on treatment in the extension phase, receiving deferasirox for a median of 2.6 years. Median baseline SF values in the three dose cohorts were 1932, 2527 and 4158 ng/mL, respectively. During the core and extension phases, SF levels decreased in patients who received deferasirox 30 mg/kg/day and were maintained in patients who received 20 mg/kg/day. In contrast, SF steadily increased in patients who initially received 5/10 mg/kg/day. Subsequent dose escalation during the extension phase generally resulted in decreased SF levels (see shaded area of Table), returning close to baseline by data cut-off. A similar pattern was observed irrespective of age or underlying anemia. Table. Median change from baseline in S:F (ng/ml) during deferasirox treatment of up to 2.6 years (n=480) A further 258 patients (deferoxamine arm in core phase) crossed over to deferasirox during the extension phase, receiving deferasirox for a median of 1.6 years. Comparable responses were observed in these patients versus those in the deferasirox cohort at corresponding doses. Conclusions: SF steadily decreased following dose increases in regularly transfused patients who initially received deferasirox 5/10 mg/kg/day. This analysis confirms that 30 mg/kg/day effectively reduces body iron over the long term, whereas 20 mg/kg/day is effective in maintaining body iron levels in regularly transfused patients. Deferasirox dose can therefore be effectively tailored depending on the goal of therapy (maintenance or reduction in body iron levels).

Serum Ferritin in Children with Sickle Cell Disease on Chronic Transfusion: Measure of Iron Overload or End Organ Injury? STOP/STOP II Liver Iron Ancillary Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 791-791 ◽  
Author(s):  
Tom Adamkiewicz ◽  
Miguel R. Abboud ◽  
Julio C. Barredo ◽  
Melanie Kirby-Allen ◽  
Ofelia A. Alvarez ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Iron Removal ◽  
Organ Injury ◽  
Cell Disease ◽  
Liver Iron ◽  
Flow Measurements ◽  
Transfusion Therapy

Abstract Between 1995 and 2004, two NIH-sponsored studies (STOP/STOP II) showed that children with sickle cell disease (SCD) and abnormal transcranial Doppler blood flow measurements (high stroke risk) are protected from stroke with regular blood transfusions. Iron overload, which may lead to complications and requires iron removal therapy, was monitored by serum ferritin (SF). Liver iron concentration (LIC) measurement was not mandated by protocol and was performed at investigator discretion. Biopsy dates and lab values were captured during STOP/STOP II, providing an opportunity to validate SF against LIC. 75 LICs on 36 patients (19 female, 17 male) at 8 centers were obtained. No liver biopsy complications were reported. LICs were correlated with STOP/STOP II core laboratory SF and alanine aminotransferase (ALT) obtained within 180 days of LICs. Median age at first biopsy was 11.1 years (range, 4.5–17.8), median time from start of transfusion was 36 months (range, 2–100). Iron removal treatment was initiated a median 23 months (range, 4–108) from start of transfusion, with deferoxamine (n=27), and/or exchange transfusion (n=9). 21 pts (58%) had multiple LIC measures: 2 (n=9), 3 (n=8), 4 (n=2), 5 (n=2). Last LICs on iron removal therapy were obtained a median 72 months (range, 35–124) from start of transfusion. Correlation between SFs and LICs were r=-0.06 (n=18) for first LICs obtained prior to iron removal therapy, r=0.50 (n=17) for last LICs obtained on iron removal therapy, and r=0.51 for all LICs (n=60). Pts with single/last LIC >=15 mg/gram dry liver were significantly more likely to have ALTs >=45 IU/L compared to those with LICs <15 mg/gram (5/12 vs. 1/18; odds ratio 12.1; 95% CI 1.2–123.6; p=0.03). Pts with LIC >=15 mg/gram and ALT >=45 IU/L tended to have higher SFs then those with normal ALT (mean SF 4927 ng/ml, 95% CI 1739–8115 vs. mean SF 2255 ng/ml, 95% CI 1599–2912). 37% (7/19) of pts with LIC >=15 mg/gram had SFs <2000 ng/ml. 55% (11/20) of pts with repeated LICs, had last LICs <15 mg/gram after initiation of iron removal therapy. SF did not correlate with LICs after initiation of blood transfusion therapy and correlated weakly after initiation of iron removal therapy. Over 1/3 of children with evidence of significant iron overload, as measured by LICs, had low serum SFs (<2000 ng/ml), leading to a potentially erroneous interpretation of low iron stores. A significant portion of pts with elevated LICs had evidence of liver injury (ALT elevation). SF elevation observed in some pts may be due in part to end organ injury. Sustained iron overload control was achieved in over 1/2 of pts examined with repeated LICs.

Serum Ferritin Predicts Liver but Not Cardiac Iron Burden by Noninvasive MRI in Sickle Cell Disease (SCD.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1421-1421 ◽  
Author(s):  
Robert I. Liem ◽  
Cynthia Rigsby ◽  
Richard J. Labotka ◽  
Andrew DeFreitas ◽  
Alexis A. Thompson
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Content ◽  
Iron Loading ◽  
Cell Disease ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Liver Iron Content ◽  
The Mean

Abstract BACKGROUND: Assumptions about iron loading as well as the utility of ferritin to predict transfusional iron overload among individuals with sickle cell disease (SCD) are largely based on extrapolation from data generated in patients with thalassemia major (TM). Yet recent studies suggest the natural history of iron overload in patients with SCD differs significantly from chronically transfused patients with TM. We sought to evaluate the extent of myocardial and hepatic siderosis using noninvasive imaging in chronically transfused patients with SCD and examine its clinical associations, including relationship to long-term trends in serum ferritin, transfusion history, chelation status and markers of hemolysis and inflammation. METHODS: We evaluated 17 subjects (mean age 15±3.6 yrs, range 9 to 20). The mean transfusion duration was 7.3±3.6 yrs (range 2 to 15). Thirteen (76%) patients were on chelation with deferasirox at the time of screening; 4 were not on chelation Rx. MRI T2*/R2* of the heart and liver using a multiple gradient echo sequence was performed on a single 1.5T GE scanner. Hepatic iron concentration (HIC) values were predicted from liver R2* values. RESULTS: Mean HIC in subjects was 9.9±6.7 mg/gm liver dry weight (range 2.5 to 20.8) and was ≥15 mg/gm in 6/17 (35%) subjects. The mean long-term serum ferritin (past 5 yrs, or duration of transfusion if < 5yrs) was 2318±1122 ng/mL (range 541 to 4225). Using Pearson’s correlation coefficient, we observed a significant relationship between HIC and ferritin (r=0.765, p=<0.001). We generated a receiver operator characteristic (ROC) curve to assess the utility of ferritin as a predictor of elevated HIC, using a threshold HIC thought to predict serious iron-related complications. A ferritin cut-off value ≥2164 ng/mL correctly identified 80% of cases of HIC ≥15 mg/gm (AUC 0.96, p=0.003) in our subjects with 83% sensitivity and 73% specificity. Despite markedly elevated HIC and ferritin values in some subjects, none had myocardial siderosis. All 17 subjects had cardiac MRI T2* values in the normal range > 25 ms. Cardiac iron load measured by T2* did not correlate with HIC or serum ferritin. We examined C-reactive protein (CRP) and B-type natriuretic peptide (BNP) as markers for inflammation and myocardial strain, respectively, in our subjects but neither demonstrated a significant relationship to ferritin or MRI findings. BNP, however, did correlate modestly with both age (r=−0.574, p=0.013) and left ventricular ejection fraction on cardiac MRI (r=0.510, p=0.036). A subset of subjects (n=8) had histologic iron measurements by percutaneous liver biopsy (LBx) within 6 months of MRI. While liver iron content by LBx correlated significantly with HIC by MRI (r=0.759, p=0.03), liver iron content by LBx did not correlate with ferritin (r=0.312, p=0.452). CONCLUSION: We found that serum ferritin is a good predictor of liver iron by MRI R2*, and that long term ferritin values ≥2164 ng/mL predict significant hepatic iron overload as assessed by this noninvasive method. We did not observe appreciable cardiac iron loading in our subjects with SCD, which otherwise might have been predicted by elevated HIC alone, as in individuals with TM. These data suggest that reliable, long term surveillance of transfusion-induced iron overload in SCD may be achieved using serum ferritin and HIC by MRI R2* as surrogate markers of hepatic siderosis rather than relying on liver iron content measured invasively by LBx. Also, previously determined thresholds for significant cardiac iron loading in TM, based on degree of hepatic siderosis, may not be applicable in SCD. Further investigation into alternative mechanisms of iron loading or distribution in these related but distinct disorders is warranted.

Correlation of Serum Ferritin Levels and Liver Iron Concentration Determined by R2* MRI in Patients with Thalassemia Intermedia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3818-3818
Author(s):  
Ali Taher ◽  
F. El Rassi ◽  
H. Ismaeel ◽  
S. Koussa ◽  
A. Inati
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Care Center ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Thalassemia Intermedia ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Cross Sectional ◽  
Transfusion Therapy

Abstract Background: Unlike patients with thalassemia major (TM), those with thalassemia intermedia (TI) do not require regular blood transfusion therapy but remain susceptible to iron overload due to increased intestinal iron uptake triggered by ineffective erythropoiesis. TI patients can accumulate 1–3.5 g of excess iron per year, and effective monitoring of iron burden is an important element of patient management. Assessment of serum ferritin (SF) levels is a convenient and widely used method, and a correlation between SF and liver iron concentration (LIC) has been demonstrated in patients with TM. SF levels may, however, be a poor indicator of LIC in patients with TI and the limited data available on the SF:LIC correlation prove equivocal; in fact, reports suggest a discrepancy between LIC and SF in patients with TI. This is the largest study to use R2* MRI to evaluate the SF:LIC correlation in patients with TI. Methods: This was a cross-sectional study of randomly selected, infrequently/non-transfused TI patients treated at a chronic care center in Hazmieh, Lebanon. Patient charts were reviewed and a medical history was compiled. Blood samples were taken for SF assessment, and LIC was determined by R2* MRI. Results: Data from 74 TI patients were included in this analysis (33 male, 41 female; mean age 26.5 ± 11.5 years). Of this group, 59 (79.7%) patients were splenectomized, 20 were transfusion-naive, 45 had received several transfusions in their lifetime but none in the past year, and 9 patients were regularly transfused 2–4 times per year. Overall mean SF values were 1023 ± 780 ng/mL (range 15–4140); mean LIC levels were 9.0 ± 7.4 mg Fe/g dry weight [dw] (range 0.5–32.1). In contrast to previous findings, a significant positive correlation between mean LIC and SF values was seen in the whole group (R=0.64; P<0.001), and in a subset of splenectomized patients (R=0.62; P<0.001). In comparison with data obtained from a randomly selected group of patients with TM treated at the center, SF levels in TI were seen to be significantly lower, while the mean LIC values were similar in both groups of TI and TM. For a given LIC, SF values were lower in patients with TI than those with TM (Figure). Conclusions: Evaluation of iron levels shows that many patients with TI have SF and LIC levels above the recommended threshold levels, indicating a risk of significant morbidity/mortality. Similar to TM, a significant correlation between SF and LIC was observed in patients with TI; however, the relationship between SF and LIC was different between TI and TM (for the same LIC, the SF values in TI were lower than those in TM). Therefore, use of the current threshold for iron overload based on SF values in TM will lead to significant underestimation of the severity of iron overload in patients with TI. This may result in delayed chelation therapy, and expose patients to morbidity and mortality risks associated with iron overload. Disease-specific management approaches are therefore required in patients with TI. This includes either regular assessments of LIC, ideally by non-invasive R2* MRI, or lowering the SF threshold for initiating iron chelation in patients with TI. Figure Figure

Vitamin C Deficiency in Patients on Long-Term Deferasirox without Supplementation.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1858-1858
Author(s):  
Konstantinos Sarantos ◽  
Patricia Evans ◽  
Maciej Garbowski ◽  
Bernard Davis ◽  
John B Porter
Keyword(s):  
Vitamin C ◽  
Iron Overload ◽  
Serum Ferritin ◽  
Plasma Levels ◽  
Plasma Vitamin ◽  
Liver Iron ◽  
Vitamin C Deficiency ◽  
Vitamin C Supplementation ◽  
Iron Excretion

Abstract Background: Under conditions of iron overload, ascorbic acid is oxidised at an increased rate leading to a risk of vitamin C deficiency. With deferoxamine (DFO) standard therapy, vitamin C is usually given at a dose of 2–3mg/kg on the days of DFO infusion as this increases iron excretion by up to 30%. With deferarisox (DFX) chelation treatment, although supplementation is permitted, there is currently no information about the effects of vitamin C supplementation on iron excretion and it is often left to patients or their clinician’s discretion as to whether supplementation is given. With long-term treatment, in the absence of supplementation there is a potential risk that vitamin C deficiency will develop and this could influence response to treatment. Patients and Methods: We have measured fasting plasma vitamin C in 41 patients who have been on long term deferasirox treatment for transfusional iron overload for between 1.5 and 5 years. 32 of these patients had received no supplementation and 9 patients had received 2–3 mg/kg/ day of supplementation. We have examined whether trends in serum ferritin, myocardial T2* and liver iron, during the final year of observation, relate to plasma levels of vitamin C. Results: Fasting plasma Vitamin C was significantly lower in the 41 patients (mean=30.3μmol/l, SD=20.8) than healthy control patients (mean=60.29μmol/l SD=12.6) (P<0.0001). Fasting vitamin C levels were significantly lower in patients without supplementation (mean=26.1μmol/l, n=32) (p=0.011) than in patients who received regular supplementation (mean=45.5μmol/l, n=9). In the 32 patients without supplementation 23 (72%) had plasma levels less than two standard deviations from the control mean. Fasting vitamin C levels after a minimum of 1 year treatment without vitamin C supplementation negatively correlated with liver iron concentration as estimated by T2* MRI. One patient, who was subsequently found to have the lowest fating vitamin c level (2.9μmol/l) developed clinical signs consistent with scurvy with severe gum disease requiring dental clearance. We found no difference in the change of ferritin trend, LIC decrease or cT2* trend in the patients receiving supplementation from those who did not. We found that the correlation between LIC and serum ferritin was less clear in deficient patients (<36μmol/l or 2SD from the mean, r=0.51, p<0.01) than replete patients (>36μmol/l) (r=0.88, p<0.0001). Conclusions: We conclude that with long-term deferasirox therapy without vitamin C supplementation, there is a significant risk of vitamin C deficiency with a potential for clinical scurvy. The risk of ascorbate deficiency is further increased at higher levels of body iron loading. These findings suggest that vitamin C supplementation (2–3mg/kg/day) should be recommended as standard for patients on long-term chelation therapy with deferasirox. It would also be of value to determine whether long term-response was improved by ascorbate supplementation.

scholarly journals 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

2018 ◽  
Vol 10 ◽  
pp. e2018064 ◽  
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.

scholarly journals Stratification for Age in Transfusion-Dependent Thalassemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3638-3638
Author(s):  
Alessia Pepe ◽  
Laura Pistoia ◽  
Mario Rocca ◽  
Giovanni Palazzi ◽  
Francesco Sorrentino ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Cardiac Complications ◽  
Liver Iron ◽  
Number Of Patients ◽  
Cardiac Iron Overload ◽  
Group 2 ◽  
Magnetic Resonance Imaging Mri ◽  
Group 1

Abstract Introduction. Transfusion-dependent β-thalassemia (TDT) is the most severe clinical form of β-thalassemia and requires regular long-term red cell transfusions for survival. This study aimed to examine the association of age with the presence of iron overload assessed by Magnetic Resonance Imaging (MRI) and cardiovascular and endocrine complications in TDT patients. Methods. We considered all TDT patients enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) project at the first MRI examination. Iron concentrations were measured by T2* multiecho technique. All complications were classified according to international guidelines. Results. Three groups of patients were identified: age<12 years (group 0, N=53), age between 12-17 years (group 1, N=100) and age≥18 years (group 2, N=1857). The number of transfusional units in the 12 months before the MRI scan resulted significantly lower in group 0 versus both group 1 (20.8±5.3 vs 34.8±10.6; P<0.0001) and group 2 (20.8±5.3 vs 39.2±10.9; P>0.0001) and in group 1 versus group 2 (P=0.021). The Table shows the comparison of clinical characteristics among the 3 groups. Serum ferritin levels were significantly higher in both groups 0 and 1 when compared to group 2. Liver aminotransferases were significantly lower in group 1 than in group 2. The number of patients with MRI LIC (liver iron concentration) >3 mg/g dw was significantly higher in group 1 than in group 2 and the number of patients with global heart T2*<20 ms was significantly lower in group 0 than in group 2. Among the endocrinopathies, hypogonadism, hypothyroidism and osteoporosis were significantly less frequent in groups 0 and 1 than in group 2 while diabetes was significantly less frequent only in group 1 when compared to group 2. Frequency of heart failure was comparable among the groups while the frequency of arrhythmias was significantly lower in group 1 than in group 2. The types of chelation regimens were significantly different among groups (<0.0001) (see Figure). Conclusions. Younger patients had more hepatic iron, despite the significant lower transfusional burden. Cardiac iron overload occurs early in TDT patients but it is more frequent in older patients. Endocrinopathies (excluding diabetes) and cardiac complications become clinically evident during the second decade and are time-dependent processes. Our data suggest the need for an effective strategy to prevent iron overload since early childhood, in order to reduce its toxic effect and prevent the development of long-term complications. Figure. Figure. Disclosures Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.

scholarly journals Transfusional Iron Overload in Sickle Cell Patients:Outcomes of Chelation Therapy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4177-4177
Author(s):  
Daniel Adamkiewicz ◽  
Abhishek A. Mangaonkar ◽  
James Son ◽  
Hongyan Xu ◽  
Leigh Wells ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Serum Ferritin ◽  
Chelation Therapy ◽  
Conflicts Of Interest ◽  
Chelating Agent ◽  
Regulatory Peptides ◽  
Beta Thalassemia ◽  
Glycoprotein Hormone ◽  
Liver Iron ◽  
Number Of Patients

Abstract Iron (Fe) overload is not rare among sickle cell disease (SCD) patients. It results from either chronic transfusions for primary or secondary stroke prevention, or more commonly sporadic, mostly unnecessary transfusions and are associated with significant morbidity, secondary to hepatic, cardiac and renal Fe deposition. Previous studies at our Center showed that 12% of the adult SCD population had Fe overload, and vast majority of these (80%) resulted from episodic transfusions (Son et al, 2013). Subsequent studies showed that the Fe regulatory peptide, hepcidin was appropriately upregulated in SCD subjects with Fe overload, and the plasma levels of the glycoprotein hormone erythroferrone (ERFE) was not as high as that found in patients with transfusion dependent beta thalassemia (TDT) due to the absence of significant ineffective erythropoiesis in SCD (Thawer et al, 2017, Mangaonkar et al, Brit. J. Haematol, 2020). We report on the utilization and outcomes in Fe overloaded SCD patients who were prescribed the oral chelating agent deferasirox. 22 patients were prescribed deferasirox; median age was 38, 12 female 10 male. 21 had Hb SS, and 1 had s-b 0 thalassemia. Deferasirox dose ranged from 720-2500 mg/day (12 to 28 mg/Kg/day). Nonadherence was ascertained by patients' own admission. Figures 1-3 show the pre and post ferritin levels in subjects who were on deferasirox, and in controls; patients who took deferasirox had a more pronounced decrease in their ferritin (p=.004 vs p=.74). Although hepatic MRI for liver iron content (LIC) was not available on all patients, in those who underwent MRI there was a correlation between LIC and serum ferritin obtained at close temporal proximity (Fig. 4). Most common side effects of deferasirox were gastrointestinal (abdominal pain, nausea, vomiting, diarrhea), which were seen less commonly with the newer oral formulation (Jadenu). Several conclusions can be drawn from our observation on relatively small number of patients: 1) Deferasirox is effective in decreasing Fe overload as shown by serum ferritin levels 2) Second generation of oral deferasirox is better tolerated, and therefore is associated with improved adherence, 3) Documentation of a decrease in LIC with chelation will be important for the reversal of Fe induced organ damage, and 4) Parallel studies of the levels of Fe regulatory peptides hepcidin and erythroferrone (ERFE) will clarify the effect of chelation therapy on biomarkers of Fe metabolism. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Disparities in Criteria for Initiating Chelation Therapy for Iron Overload in Patients with Myelodysplastic Syndromes (MDS).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2535-2535 ◽  
Author(s):  
John M. Bennett ◽  
Alan F. List ◽  
Keyword(s):  
Serum Ferritin ◽  
Chelation Therapy ◽  
Transferrin Saturation ◽  
Clinical Signs ◽  
Iron Chelation ◽  
International Prognostic Scoring System ◽  
Quantitative Ct ◽  
Liver Iron ◽  
Number Of Patients ◽  
Sole Criterion

Abstract In the majority of MDS cases, isolated anemia is the only clinical evidence of impaired hematopoiesis at the time of MDS diagnosis. It is estimated that >40% of MDS patients require regular red blood cell transfusions during some stage of their disease. Findings from The MDS Foundation’s 2004–2005 Practices & Treatment Survey indicate that a substantial proportion of MDS patients in all International Prognostic Scoring System (IPSS) risk groups are transfusion-dependent: Low, 30%; Intermediate-1, 50%; Intermediate-2, 70%; High, 90% (median values). Seventy (38 US and 22 international) of the MDS Foundation’s102 Centers of Excellence responded to the survey as of July 1, 2005. Survey responses revealed that an average of 30% of transfusion-dependent patients receive parenteral iron chelation therapy (median, 20%; range: 3–100%) and that the criteria for initiating chelation therapy are not uniform. The number of transfusions was reported as a determining criterion by 46% of respondents, with a mean number of 35 transfusions (median, 30; range: 4–100). 15% of respondents indicated at the number of transfusions was the sole criterion used. Serum ferritin levels were reported as a determining criterion by 57% of respondents, with the following cutoff values: Ferritin concentrations for initiating chelation therapy *% respondents using this cutoff as criterion >1000 ng/mL 41%* >1500 ng/mL 11% >2000 ng/mL 37% Other (>3000, unspecified) 9% 32% of respondents indicated that serum ferritin was the sole criterion used. (Irrespective of chelation therapy, 92% indicated that they monitored ferritin levels in transfusion-dependent patients.) Other criteria used to determine start of chelation therapy included age/life expectancy, MDS subtype, clinical signs of hemochromatosis, quantitative CT liver iron estimation, liver function, transferrin saturation >50%, BMT, anticipated chronic transfusion need, and logistical issues and insurance coverage. A combination of criteria was reported to be used by 38% of respondents. The majority of respondents (90%) reported that they would increase the number of patients on chelation therapy if an oral agent were available. Although the decision for initiating chelation therapy in transfusion-dependent anemic MDS patients is individualized because of the heterogeneous patient population, this data analysis suggests a need for the standardization of select criteria (e.g., number of transfusions, serum ferritin).

Sign in / Sign up

Export Citation Format

Share Document