Iron Chelation Treatment with Oral Solution of Deferiprone in Young Children with Hemoglobinopathies,

Abstract Abstract 3204 Background - Aim. Children with transfusion dependent hemoglobinopathies rapidly develop iron overload in vital organs and iron removal with chelating agents is required early in life and in some cases after the age of 2. The oral administration of iron chelation is most welcome by thalassemic children and their parents who have problems with the discomfort and side effects of deferoxamine injections. Deferiprone, previously only in tablet form, was not suitable for young children under the age of 5 years. Recently the solution form of deferiprone has been introduced. There are limited clinical data on the safety and efficacy of deferiprone at a very young age. The aim of our study was the presentation of data regarding the safety and efficacy of liquid oral solution of deferiprone in young children with hemoglobinopathies less than 10 years old. Patients and methods. Nine young children (5 boys, 4 girls) receiving oral solution of deferiprone (Ferriprox® 100 mg/mL) were studied. The mean age at the beginning of the treatment was 6.5 (range 2–10). Six children had beta-thalassemia major, 1 thalassemia intermedia and 2 sickle cell/beta thalassemia. The mean number of red blood cell transfusions during the previous year was 10.6 (range 8–15). All the children had chronic iron overload requiring chelation therapy, as defined by serum ferritin concentration [mean ± standard error (SE): 2440±1275 μg/L]. All children were naïve to iron chelation therapy before this study, except for 2 patients who were on deferoxamine (mean dose=35 mg/kg/day; mean duration of use=1.5 years). One child was splenectomized. All children had negative anti-hepatitis C antibody status at baseline. Treatment was initiated at a daily dose of 50 mg/kg, divided into 3 doses, for the first 2 weeks. The dose was increased to 75 mg/kg, for another 2 weeks. If serum ferritin concentration at baseline was greater than 2500 μg/L, the dose was further increased to a total daily dose of 100 mg/kg after 4 weeks therapy. After initiation of the treatment, full blood count was assessed weekly, serum ferritin monthly, and liver and renal function bimonthly. The mean duration of treatment was 9.5 months (range 2–15 months). To evaluate the efficacy and safety of oral deferiprone treatment, biochemical parameters such as serum ferritin and liver enzymes were analyzed using the Student t-test. All parameters are presented as mean± SE. P-values less than 0.05 were considered statistically significant. Results. All children received the oral deferiprone without any problems of compliance. The hematological and biochemical markers during treatment are shown in Table 1. Adverse reactions to deferiprone were mild and transient: abdominal discomfort and diarrhea at initiation of therapy (1 child) and mild neutropenia (1 child) resolved within 8 days with no need of discontinuation of treatment. Deferiprone oral solution was effective in reducing serum ferritin (mean±SD) (initial 2440±1275 μg/L vs final 2030±915 μg/L, p<0.005) (Figure 1). Five children of the study were <6 years old. The baseline serum ferritin of these children was significantly lower than older children (2250 μg/L±880 vs 2950 μg/L±1550, p<0.005). The differences in changes in serum ferritin did not reach statistical significance. Conclusions. This small study shows that oral solution of deferiprone was well tolerated by young children and its use was not associated with major safety concerns. Furthermore, it was effective in decreasing serum ferritin. Further studies with large number of patients and longer follow-up, are needed to confirm the safety and efficacy profile of deferiprone in childhood. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

The Tolerability, Safety and Efficacy of a New Oral Solution of Deferiprone in Children with Transfusional Iron Overload

Blood ◽

10.1182/blood.v112.11.5373.5373 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5373-5373

Author(s):

Mohsen Saleh El-Alfy ◽

Teny Tjitra Sari ◽

Lee Lee Chan ◽

Fernando Tricta ◽

Amal El-Beshlawy

Keyword(s):

Young Children ◽

Iron Overload ◽

Serum Ferritin ◽

Neutrophil Count ◽

Older Patients ◽

Adverse Reactions ◽

Oral Solution ◽

Tablet Formulation ◽

Limiting Factor ◽

Safety And Efficacy

Abstract Although there are 20 yr of clinical experience with deferiprone in treating transfusional iron overload, limited data exist on the safety and efficacy of deferiprone in very young children. Difficulties in swallowing the tablet formulation of deferiprone (Ferriprox®, ApoPharma, Canada), is a limiting factor in the administration of deferiprone in young children. The current study evaluated the tolerability, safety and efficacy of a new liquid formulation of deferiprone (Ferriprox® Oral Solution) in iron-overloaded pediatric patients with transfusion-dependent anemias (≥ 8 transfusions/year). The study also assessed the daily neutrophil count in patients who continued deferiprone therapy during episodes of mild neutropenia. The study was approved by the relevant regulatory authorities and ethics review boards. Informed consent was obtained from the patients’ legal representatives. One-hundred children [91Thal major, 8 HbE, 1 Sickle Cell disease; 46 female and 54 male; 76 Caucasian (Egyptian), 24 Asian (9 Chinese, 13 Indonesian, 2 Malay)] ranging from 1 to 10 yr of age (median 5.0 yr) were enrolled. At enrollment, 51 children were being treated with deferoxamine (mean duration 1.82 ± 1.95 years; range 0.1–7.3 yr), 20 with deferiprone (mean duration 0.5 ± 0.6 yr; range 0. 04–2 yr), 8 patients with deferasirox (mean duration 0.4 ± 0.5 yr; range 0.1–1.6 yr) and 21 patients were naïve to chelation therapy. Deferiprone therapy was initiated at 50 mg/kg/day, divided in 3 doses, for the first 2 weeks, and then increased to 75 mg/kg/day. The dose was further increased to 100 mg/kg/day for those patients with ferritin > 2500 μg/L at baseline. Ninety-five children completed 6 months of therapy. One patient was lost to follow-up, 2 patients voluntarily withdrew consent (1 patient disliked the taste, 1 patient did not comply with weekly visits), and 2 were withdrawn due to adverse events. Therapy with the oral solution of deferiprone was not associated with unexpected adverse reactions. The incidence of gastrointestinal adverse reactions was lower than observed for the tablet formulation in older patients (Table). Oral solution in children ≤ 10 yr old Tablet formulation in children > 6 yr old and adults Adverse Reaction (AR) % Patients with AR % Patients with AR Nausea 1% 16% Abdominal Pain 6% 14% Vomiting 6% 12% Arthralgia 4% 11% Neutropenia (0.5 × 109/L ≤ ANC < 1.5 × 109/L) 6% 6% Agranulocytosis (0.5 < ANC) 2% 1% Five patients experienced single episodes of mild neutropenia [absolute neutrophil count (ANC) 1.5 × 109/L but not less than 1.0 × 109/L], which resolved and did not recur, despite continuous deferiprone use. Another patient experienced 2 transient episodes of mild neutropenia and a third episode that progressed to agranulocytosis (ANC < 0.5 × 109/L). Deferiprone was discontinued and the patient was treated with G-CSF. The event resolved (ANC > 1.5 × 109/L) within 9 days upon discontinuation of deferiprone. Another patient experienced a single episode of agranulocytosis, which resolved within 9 days upon discontinuation of deferiprone and therapy with G-CSF. During the 6-month therapy, there was a significant decrease in serum ferritin from a mean baseline value of 2532 ± 1463 to 2176 ± 1144 μg/L (p< 0.0005). The new oral solution of deferiprone was well tolerated and effective in lowering serum ferritin in young children with transfusion dependent anemias and exhibited a safety profile similar or better to that reported for the tablet formulation in older patients. The results also suggest that not all episodes of mild neutropenia progress to agranulocytosis with continued deferiprone therapy, and that further studies are warranted to differentiate those patients from those at risk of developing deferiprone-induced agranulocytosis following neutropenia. This study includes the first report of patients using deferiprone as their first iron chelator.

Download Full-text

The Correlation Of Hepatic Iron Loading Determined By Magnetic Resonance Image and Serum Ferritin In Patients With Beta-Thalassemia Intermedia

Blood ◽

10.1182/blood.v122.21.2203.2203 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2203-2203

Author(s):

Ampaiwan Chuansumrit ◽

Jiraporn Laothamathat ◽

Nongnuch Sirachainan ◽

Pakawan Wongwerawattanakoon ◽

Praguywan Kadekasem ◽

...

Keyword(s):

Blood Transfusion ◽

Serum Ferritin ◽

Iron Chelation ◽

Dry Weight ◽

Beta Thalassemia ◽

Hepatic Iron ◽

Iron Loading ◽

Thalassemia Intermedia ◽

The Mean ◽

Mri Study

Abstract Background Current practice of starting iron chelation when ferritin values reach 1,000 mcg/l has been given to patients with thalassemia disease. The body iron load in patients with thalassemia intemedia can be different from other severe thalassemia disease due to the increased intestinal iron absorption. Objective The correlation of hepatic iron loading determined by magnetic resonance image study (MRI) and various parameters was calculated. Materials and Methods MRI study, using CRMtool to determine the myocardial and hepatic iron loading, was performed in pediatric patients with beta-thalassemia intermedia. The amount of blood transfusion and duration of iron chelation were recorded. The levels of serum ferritin as well as the transfusion-transmitted diseases were checked twice yearly. Results In all, 40 patients (19 males, 23 females) manifested as beta-thalassemia intermedia were enrolled in the study. They included beta thalassemia/HbE disease (n=37) and beta thalassemia major (n=3) with the mean age of 14.9±3.6 years. Three patients with beta-thalassemia major behaved as beta-thalassemia intermedia since two patients carried the combination of beta-thalassemia0 and beta-thalassemia+ genes while another patient had an additional alpha-thalassemia gene. The remaining patients possessed the combination of beta-thalassemia genes at codon 41/42 (4 base pair deletion) and HbE gene at codon 26 (GAG>AAG). All patients received routine hepatitis B vaccination. None had positive serological testing for HBsAg, antiHCV or antiHIV. They required regular transfusion to maintain their pre-transfusion hematocrit at 24% starting at the mean age of 4.1±3.3 years with the mean duration of 10.1±4.6 years. Nineteen were splenectomized at the mean age of 8.0±3.1 years. They all received iron chelation of 10-12 hours of desferrioxamine subcutaneous injection, oral deferiprone ingestion or the combination of desferrioxamine and deferiprone starting at the mean age of 9.1±3.8 years with the mean duration of 6.2 ±4.3 years. At the mean age of 14.9±3.6 years, they underwent MRI study and revealed that the mean T2* of myocardium was 38.6±8.1 milliseconds (ms) and mean T2* of liver was 3.2±2.0 ms. Neither patients had myocardial iron loading while 36 patients had hepatic iron loading varying from severe degree of <1.4 ms (iron >10 mg/g dry weight, n=4), moderate degree of >1.4-2.7 ms (iron >5-10 mg/g dry weight, n=16) and mild degree of >2.7-6.3 ms (iron 2-5 mg/g dry weight, n=16). The results revealed no correlation of the hepatic T2* and the duration of blood transfusion (p=0.157), duration of iron chelation (p=0.071), total blood transfusion and total iron loading from transfusion (p=0.471) one-year blood transfusion and one-year iron loading from transfusion (p=0.321) except for the serum ferritin (p=0.001). The geographic mean of ferritin was 1584.9 mcg/l. The hepatic iron loading by MRI was shown in the equation of T2*(ms) = 4.663-0.001ferritin (mcg/l) (r=-0.503, p=0.001). Patients with serum ferritin ≥1,000 mcg/l risked hepatic iron loading (T2*<2.7 ms, iron 5-10 mcg/g dry weight) with an odds ratio of 5.07 (95% CI 1.09-23.44). Therefore, patients with beta-thalassemia intermedia were at risk of hepatic iron overloading if the initiation of iron chelation started at the serum ferritin of 1,000 mcg/l. Conclusion The current practice of starting iron chelation when ferritin values reach 1,000 mcg/l risks hepatic iron loading in patients with beta-thalassemia intermedia. Advanced technology for evaluating hepatic iron loading is suggested. Thus, where MRI study is not feasible, serum ferritin can be used to estimate the hepatic T2*. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Effective and Safe Deferasirox Treatment of Patients with Various anemia's and Transfusional Iron-Overload in the Medical Practice: Results From Two German Observational Studies

Blood ◽

10.1182/blood.v118.21.5165.5165 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5165-5165

Author(s):

Christian Junghanss ◽

Rudolf Schlag ◽

Bernd Gaede ◽

Matthias Moelle ◽

Steffen Doerfel ◽

...

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Observational Studies ◽

Chelation Therapy ◽

Iron Chelation ◽

Iron Chelator ◽

Beta Thalassemia ◽

Final Visit ◽

Iron Chelation Therapy ◽

The Mean

Abstract Abstract 5165 Background: Progressive anaemia is highly prevalent amongst many malignant diseases leading to RBC transfusion-dependency. Therefore transfusion-related iron overload (IOL) is common in these patients (pts) and can result in multiple organ failure. Iron chelation therapy prevents organ failure, reduces the risk of infections and can improve hematopoesis in some diseases. The once-daily oral iron chelator deferasirox has been shown to reduce iron overload in pts with various transfusion-dependent anaemias assessed by serum ferritin (SF). Despite extensive knowledge of iron chelation in MDS or beta-thalassemia pts, data in pts with other anaemias is limited. Here, we present data from a subgroup of transfusion-related IOL pts that were included two non-interventional studies (EXTEND, EXJANGE) performed in Germany and who suffered from diseases other than MDS or beta thalassemia. Methods: 130 pts with various malignant diseases such as myeloproliferative disorders (43 pts, including 31 pts particular specified as myelofibrosis), acute myeloid leukaemia (14 pts), sickle cell anaemia (6 pts), aplastic anaemia (11), congenital aplastic anaemia (5) or Non-Hodgkin's lymphoma (6 pts) were treated with deferasirox in the daily-routine setting of office-based physicians and included in either the EXTEND or EXJANGE study. Patient with MDS or beta-thalassemia were also included in the studies, but are excluded from this analysis. Analysis is based on 1-year pooled data of these two, multicenter, non-interventional observational studies. Transfusion-dependent pts with IOL with or without prior chelation were enrolled and received the iron chelator deferasirox. Prescription of deferasirox, just as inclusion and exclusion criteria was in accordance with the terms of Exjade marketing authorization in the EU. Efficacy and safety parameters, including serum ferritin and adverse events (AEs), were collected in 2-monthly intervals. Results: 98 pts had no prior chelation therapy (51 M, 45 F, 2 missing; mean age 63.3, range 3.2–91.9 yrs) and a median baseline SF of 2,968 (range 561–11, 423) ng/mL. 32 pts had prior received prior chelation therapy (mainly with desferal; 17 M, 15 F; mean age 50.1, range 3.5–80.9 yrs) and a median baseline SF of 2,635 (range 539–19, 540) ng/mL. The mean number of prior red blood cell transfusions was 55. The mean prescribed daily dose of deferasirox at the first visit was 16.3 mg/kg/d rising up to 18.1 mg/kg/d after 12 months. During treatment, median SF levels clearly decreased from first to final visit [-806 ng/mL; p<0.0001 (explorative analysis)] in the chelation-naïve and also in the pre-chelated population [-300 ng/ml; p = 0.1705 (explorative analysis)]. The median observation period and days on therapy was 349 and 343 days, respectively. At final visit 74 pts (56.9%) were still on deferasirox therapy. Reasons for discontinuation by the final visit included 19 AEs (35.2%). 45 pts (34.6%) experienced an investigator assessed drug-related AE. The most common drug-related AEs were diarrhea (n=17; 37.8%), nausea (n=11; 24.4%) and blood creatinine increased (n=6; 13.3%). As in previous clinical trials, serum creatinine clearances showed a minor decrease over the study period (median decrease until final visit: 4 ml/min). Conclusion: Our analysis confirmed that deferasirox is effective and well tolerated in chelation-naïve as well as in previously chelated pts with transfusion-related IOL and diseases other than MDS or beta thalassemia. As baseline serum ferritin values were >2,500 ng/mL even in pts with prior chelation therapy, adequate chelation treatment should be considered earlier at a serum ferritin >1,000 ng/mL in pts with transfusion-dependent IOL for adequate iron chelation therapy. Disclosures: Junghanss: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Haus:Novartis Pharma: Employment. Junkes:Novartis: Employment. Leismann:Novartis: Employment.

Download Full-text

Real-World Experience of Switching from Deferasirox Dispersible to Film-Coated Tablets: Impact on Adherence to Chelation Therapy, Iron Overload and Renal Function

Blood ◽

10.1182/blood-2018-99-119030 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1062-1062

Author(s):

Simon Cheesman ◽

Raakhee Shah ◽

Sara Trompeter ◽

Perla Eleftheriou ◽

Bernadette Hylton ◽

...

Keyword(s):

Renal Function ◽

Serum Creatinine ◽

Iron Overload ◽

Serum Ferritin ◽

Patient Adherence ◽

Beta Thalassemia ◽

Daily Dose ◽

Baseline Values ◽

The Mean ◽

The Impact

Abstract Background Chronic iron overload is an important complication of long-term blood transfusions for severe beta-thalassemias, sickle cell disease and other blood disorders. Iron chelation therapy (ICT) is required to bind and excrete excess iron, which would otherwise accumulate and lead to organ damage or failure. Deferasirox is a once-daily, orally administered ICT approved for the treatment of chronic iron overload due to frequent blood transfusions in patients with beta-thalassemia major and other anaemias. A film-coated tablet (FCT) formulation was launched in the UK in 2016 and replaced the dispersible tablet (DT) formulation. In the context of a randomised clinical trial, the FCT formulation showed greater adherence and patient satisfaction, better palatability and fewer tolerability concerns than the DT. Furthermore, treatment compliance by pill count was higher with FCT (92.9%) than with DT (85.3%) (Taher et al, 2017). Little information exists however about compliance, efficacy and tolerability outside of a clinical trial setting. Objectives We wished to assess in a 'real world' situation, the effects of switching the deferasirox formulation from DT to FCT on patient adherence to ICT, iron overload and renal function. Methods Patients receiving ICT with deferasirox who were switched from the DT to FCT formulations were followed over a 12-month period and results audited using hospital dispensing and biochemistry records. The date of the first FCT prescription was defined as baseline. The initial daily dose used for switching from DT to FCT was as per manufacturer's recommendations: 70% of the DT daily dose. The impact on iron overload was assessed by comparing serum ferritin levels at 3, 6, 9 and 12 months post-switch with baseline values. The impact on renal function was assessed by comparing serum creatinine levels at 3, 6, 9 and 12 months post-switch with baseline values as well as the number of serum creatinine increases of 30% or greater above baseline. The changes in serum ferritin and creatinine were subsequently analysed by paired t-test. The Proportion of Days Covered (PDC) was calculated as a measure of patient adherence to ICT in the 12 months before and after switching formulations. Results 74 patients switched from deferasirox DT to FCT with the following diagnoses: beta-thalassemia (n = 45), sickle-cell disease (9), thalassemia-intermedia (6), HbE-thalassemia (5), other transfusion-dependent disorders (9). The median age was 36 (range: 1-78yo), mean baseline serum ferritin was 2767µg/L (range: 412-8742), mean baseline creatinine was 64.5 umol/L (range: 17-140) and the median prescribed daily dose of DT was 1250mg (range: 62.5 - 3500). The mean PDC in the 12 months prior to switching formulations was 0.80 (range: 0.31-1.00). This increased to 0.91 (range: 0.21-1.00) in the 12 months following the switch to FCT. The median prescribed daily dose of FCT was 900mg (range: 90 - 2520) The mean changes in ferritin and creatinine at 3, 6, 9 and 12 months post-switch are shown in the table. 6 out of 74 patients (8%) had a creatinine increase of >30% from baseline whilst receiving the FCT, occurring after an average of 120 days (range: 30-260). All 6 patients were managed by dose adjustment of FCT and creatinine returned to the normal range in 5 out of 6 cases. Conclusions The switch from deferasirox DT to FCT resulted in improved patient adherence to chelation, a reduction in mean serum ferritin and a modest rise in mean serum creatinine. Some patients showed a reversible rise in creatinine from baseline. The median daily dose of FCT prescribed was 72% of the DT formulation, approximately equivalent according to the known bioavailability of the different preparations and suggesting that improvements in serum ferritin were due to the more consistent daily administration of the FCT rather than an increased daily deferasirox dose. We suggest that when the fall in ferritin is abrupt and/or to levels <1000µg/L, serum creatinine should be followed particularly carefully to avoid over-exposure to deferasirox from the FCT. We further speculate that patients who may have over-reported adherence to the DT prior to switching may be most susceptible to this effect. Reference Taher, A. T., et al. (2017). "New film-coated tablet formulation of deferasirox is well tolerated in patients with thalassemia or lower-risk MDS: Results of the randomized, phase II ECLIPSE study." American journal of hematology 92(5): 420-428. Table Table. Disclosures Garbowski: Vifor: Consultancy. Porter:Novartis: Consultancy; Cerus: Honoraria; Agios: Honoraria.

Download Full-text

Do We Need the Chelation Therapy during Intensive Treatment of Acute Lymphoblastic Leukemia (ALL) in Children?

Blood ◽

10.1182/blood.v126.23.4881.4881 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4881-4881

Author(s):

Michal Romiszewski ◽

Michal Matysiak ◽

Katarzyna Pawelec

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Chelation Therapy ◽

The Body ◽

Intensive Treatment ◽

Intensive Chemotherapy ◽

Hematopoietic Stem ◽

Ferritin Concentration ◽

Serum Ferritin Concentration ◽

The Mean

Abstract Introduction Children with ALL during the intensive chemotherapy receive multiple transfusions of packed red blood cell (pRBC) that may lead to iron overload. With each transfusion of pRBC the body is supplied with an about 200-250 mg of iron, which excessive accumulation in tissues, due to the lack of mechanism for its active excretion, may cause toxic organ damage. Methods The aim of the study was to evaluate the serum ferritin concentration in children with ALL, depending on the amount of transfused pRBCs and to determine the group of patients with a risk of iron overload. The study patients included 54 children with newly diagnosed ALL treated at the Department of Pediatrics, Hematology and Oncology between 2008 and 2011, according to the ALL IC BFM 2002 therapy protocol. Prior to initiation the treatment and during the intensive chemotherapy, serum ferritin concentration and the number of pRBC transfusions (ml/kg) were assessed separately for each of the three ALL risk groups-standard risk (SR), intermediate risk (IR) and high risk (HR). Results After the intensive chemotherapy the mean ± standard deviation (SD) of serum ferritin concentration in group HR (2770 ± 1175 ng/ml) was significantly higher compared to the median in group SR 844.4 ng/ml (452.5; 1316) (p = 0.0007) and the mean ± SD in group IR-1270 ± 673.1 ng/ml (p = 0.0040). Throughout the intensive chemotherapy children in HR group received the largest volume of pRBC transfusions (ml/kg) (156.2 ± 68.31 ml/kg). In IR and SR groups the amounts of transfused pRBCs were comparable, respectively 113.5 ± 39.86 and 113.8 ± 29.56 ml/kg. Significant positive correlation was found between the serum ferritin concentration and the total amount of transfused pRBCs (ml/kg) after intensive chemotherapy (p <0.0001). After intensive treatment the concentration of serum ferritin exceeding 1000 ng/ml, that has traditionally been used as a trigger for chelation therapy, was found in 30 of 54 patients, for a prevalence in the entire cohort of 55,6% including 6 out of 6 patients in HR group (100%), 14 out of 22 patients in IR group (63,6%) and 10 out of 24 patients in SR group (41,7%). The group of patients with post-treatment serum ferritin concentration exceeding 1000 ng/mL, received significantly more pRBC transfusions (ml/kg) (139.8 ± 44.92) than the groups with serum ferritin levels between 500-1000 ng/mL (103.6 ± 18.96) (p <0.001) and <500 ng/mL-83.52 ± 17.66 (p <0.05). Conclusions These observations indicate a need of monitoring the cumulative volumes of pRBC transfusions, especially in children with ALL HR group. There is a need of routine screening for iron overload using serum ferritin in patients during intensive chemotherapy, in order to identify patients with indications for early iron chelation therapy. This is particularly important because some of them will be candidates to a hematopoietic stem cell transplantation, whereas iron overload adversely affects outcome of transplantation. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Efficient Iron Chelation Resulting in Improved Myocardial Performance with Combined Desferrioxamine and Deferiprone in Beta Thalassemia Major Patients.

Blood ◽

10.1182/blood.v104.11.3766.3766 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3766-3766 ◽

Cited By ~ 2

Author(s):

Anil V. Pathare ◽

Shahina Daar ◽

Salam Al Kindi ◽

J. David Dennison

Keyword(s):

Combination Therapy ◽

Iron Overload ◽

Serum Ferritin ◽

Iron Chelation ◽

Thalassemia Major ◽

Beta Thalassemia ◽

Myocardial Performance ◽

Beta Thalassemia Major ◽

The Mean ◽

To Receive

Abstract Background: Iron overload is the main cause of morbidity and mortality especially from heart failure in patients with beta thalassemia major [TM]. Successful iron chelation is thus essential for the optimal management of TM. Although desferrioxamine [DFX] has been the major iron-chelating treatment of transfusional iron overload, compliance is a major hindrance. The availability of oral iron chelation with deferiprone [L1] since 1987 was welcome but showed poor efficacy when used alone as compared to DFX. Aim: To compare DFX and prospective combined therapy with DFX and L1 in beta thalassemia major patients with iron overload. Methods: We studied 69 patients with beta thalassemia major (Mean age ± SD, 15.02± 5.8; Range 4–28 years) attending the Day Care unit for regular transfusional support. They received packed red cells every 3–4 weeks to maintain pre-transfusion hemoglobin concentration above 9 g/dl. They were receiving DFX at a daily dose of 40mg/kg/day by subcutaneous infusion for 8–10 hrs on 4–5 nights each week for past several years. However, owing to various reasons, they developed considerable transfusional iron overload. These patients were enrolled prospectively to receive additional therapy with oral iron chelator L1 at 75 mg/kg body weight in three divided doses with food after informed consent and also continued to receive treatment with DFX as per the above dosage. Results: Of the 69 patients, 6 developed severe GI upset, 2 developed persistently raised liver enzymes, 2 died [sepsis], two underwent bone marrow transplantation and 2 developed agranulocytosis and so did not continue in the study. In the remaining 55 evaluable patients, [3–48 months on combination therapy; mean(±SD) 22±12 months] the mean serum ferritin(±SD) fell dramatically from 3088(±1299) [DFX alone] to 2051(±935)ng/ml [DFX+L1; p<0.001], with the mean of lowest serum ferritin being 1731(±828) ng/ml in this group. Interestingly, there was also a significant improvement in the Ejection fraction [p<0.004]and Fractional shortening[p<0.0436] in these patients. Sustained successful iron chelation on combination therapy Ferritin pretherapy[DFX] 6mths[DXF+L1] 12 mths [DXF+L1] 18mths [DXF+L1] 24mths [DXF+L1] 36mths [DXF+L1] 48 mths [DXF+L1] No of Patients n=55 n=54 n=42 n=32 n=24 n=12 n=7 Mean± SD 3088±1299 2530±1221 2495±1175 2433±1154 2165±889 1686±917 997±318 Range-Max 7534 6070 5559 5126 4130 3172 1471 Range-Min 1072 599 776 408 712 473 559 Students t test[DFX v/s DFX+L1] p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001 p<0.0001 Improved myocardial performance on combination therapy Pretherapy [DFX] Combination Therapy [DFX+L1] p value Ejection Fraction [%] 69.04±5.182 72.99±5.54 p<0.0004 Fractional Shortening [%] 32.19±4.32 34.89±5.4 p<0.0436 Summary/Conclusion: The study emphasizes that beta thalassemia major patients with transfusional iron overload can be successfully treated with a combination of DFX and L1. The results also demonstrate significant statistical improvement as early as 6 months of combination therapy. Furthermore, this improvement was sustained leading to a progressive fall in the mean serum ferritin. Lastly, the study also demonstrates significant improvement in echocardiographic parameters of myocardial performance in these patients receiving combination therapy.

Download Full-text

Clinical-Reported Outcomes Of Deferoxamine Versus Deferasirox In The Treatment Of Homozygous BetaThalassemia

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v9ispl1.1382 ◽

2018 ◽

Vol 9 (SPL1) ◽

Author(s):

Zeina A Munim Al-Thanoon ◽

Mustafa Basil ◽

Nasih A Al-Kazzaz

Keyword(s):

Serum Ferritin ◽

Iron Chelation ◽

Iron Chelator ◽

Beta Thalassemia ◽

Control Group ◽

Current Standard ◽

Cross Sectional ◽

Significant Difference ◽

Multiple Blood ◽

Group 2

Iron chelation therapy with deferoxamine (DFO),the current standard for the treatment of iron overload in patients with betathalassemia,requires regular subcutaneous or intravenous infusions. This can lead to reduced quality of life and poor adherence,resulting in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia. Deferasirox (DFX) is an orally administered iron chelator that has been approved for use in many countries. The requirement of an effective,well tolerated iron chelator with a less demanding mode of administration has led to the development of deferasirox. The present study was aimed to compare the satisfaction and compliance with deferoxamine versus deferasirox (Exjade®),a novel oral iron chelator in patients with transfusion - dependent beta- thalassemia. A cross-sectional,single-center investigation study was carried out in the Thalassemia Center of Ibn-Atheer Teaching Hospital in Nineveh province,Iraq. One hundred and eight thalassemic patients aged between 2- 20 years old having received multiple blood transfusions and a serum ferritin greater than 1500 ng/ml. Patients were randomised into two groups. Group 1 received deferoxamine at a dose of 20-50mg/kg/day and group 2 received deferasirox at the dose of 10-30 mg/kg/day. Another 56 apparently healthy volunteers were used as a control group. The assessment of chelation was done during the period between November 2013 and February 2014 by measurement of serum ferritin. Satisfaction and compliance was assessed by using a special questionnaire prepared by the researcher. Out of the 108 thalassemic patients enrolled there was no discontinuation in treatment with the two drugs under study. The serum ferritin did not change significantly in any of the chelation groups. In comparison with the patients who were treated with DFO,those receiving DFX reported a significantly higher rate of compliance and satisfaction (P < 0.05). However,no significant difference was observed between the two groups regarding their satisfaction (P > 0.05).Compliance with deferasirox (50 %) was more than that with deferoxamine (20 %). Satisfaction with deferoxamine was significantly lower than deferasirox (p= 0.00).

Download Full-text