Background Patients with severe iron overload may require a more rapid and efficient therapy for reduction in iron burden than what can be provided with chelation monotherapy. Combined chelation using deferoxamine (DFO) and deferiprone (DFP) is widely used to treat such patients, but the inconvenience of parenteral administration of DFO reduces the effectiveness of this regimen in many patients. Minimal data are available on the safety and efficacy of combined two orally active chelator agents. Aim To compare the safety, efficacy, compliance, treatment satisfaction, and quality of life (QoL) associated with two combination chelation regimens: DFP and DFO versus DFP and deferasirox (DFX). Methods This was a randomized, open-label trial registered as (NCT01511848) conducted at 2 treatment centers in patients aged 10 to 18 years with β-thalassemia major and severe iron overload (serum ferritin > 2500 μg/ L on chelation monotherapy, with 50% uptrend over the last 12 months). Patients were randomly allocated to one of two 12-month treatment regimens. All patients received DFP at a dose of 75 mg/kg/day, divided into 2 doses taken orally at 8 am and 3 pm. Those in Arm 1 additionally received DFO at a dose of 40 mg/kg/d delivered via subcutaneous infusion pump, starting at 10 pm, while those in Arm 2 additionally received a dose of DFX 20 mg/kg/d, taken orally at 10 pm. The primary efficacy endpoints were the difference between treatment groups in the change from baseline to 12 months of serum ferritin (SF) levels, liver iron concentration (LIC), and cardiac MRI. Secondary efficacy endpoints were the change from baseline to 12 months in QoL, using the Medical Outcomes Study Short Form health survey (SF-36). Serum ferritin was measured every 3 months, and liver and cardiac MRI T2* assessments were conducted every 6 months. Changes in all 3 measures were compared using 2-way ANOVA for repeated measures. The safety endpoint was the occurrence of serious adverse events during the study period. In addition, patients had complete blood count every 2 weeks, and monthly detailed clinical examinations that included blood sampling for serum creatinine, albumin/creatinine ratio, and liver function tests. Audiometric and ophthalmological assessments were conducted at baseline and 12 months. Assessments of compliance and of patient-reported outcomes (PROs) were assessed at weeks 424 and at end of study. Results A total of 96 patients were randomized. The arms were comparable with respect to baseline demographics, with a mean age of 14.9±1.8 years in Arm 1 and 15.1±1.9 years in Arm 2 (p=0.27), and with 65.2% males in Arm 1 and 66.6% males in Arm 2 (p=0.76). Forty of 46 patients (87%) in Arm 1 and 46 of 48 patients (92%) in Arm 2 completed all 12 months of treatment. Reasons for discontinuation were skin infection and pain at infusion sites in Arm 1,and decrease in SF < 1000 μg/ L in Arm 2. Efficacy findings: Table 1 shows the changes in SF, LIC, and cardiac MRI values at baseline and at completion of 1 year on therapy. Safety findings: No serious adverse events were reported during the study in either treatment group. The number of adverse effects reported was comparable in both arms. Compliance: Treatment compliance was significantly higher in Arm 2 than in Arm 1(95% vs. 80%, respectively<0.001). Satisfaction: Significantly more patients in Arm 2 than in Arm 1 reported being satisfied with treatment at both 6 months (92% vs. 64%, respectively; p<0.001) and 12 months (88% vs. 59%, respectively; p<0.001). QoL: Improvement in QoL was seen in significantly more patients in Arm 2 than in Arm 1 (85% vs. 60%, respectively; p<0.001). Conclusion Data from this randomized prospective study show that while both forms of combination therapy, DFP with DFX and DFP with DFO, were effective in reducing iron overload in multi-transfused β-thalassemia major, patients who received DFP and DFX showed a higher decline in serum ferritin, greater improvement in cardiac T2*, higher treatment satisfaction, better compliance, and more improvement in QoL than did patients who received DFP and DFO, with no increased toxicity. Disclosures: No relevant conflicts of interest to declare.

Nontransfused patients with thalassemia intermedia (TI) accumulate iron due to increased gastrointestinal absorption of iron. Recent studies using T2* MRI revealed that serum ferritin does not reflect the severity of iron overload in nontransfused TI patients. We evaluated the iron overload status in TI children on monthly transfusion. Based on serum ferritin levels, 11 such patients (mean age 13.18 ± 4.09 years), were classified into two groups, group 1 (six patients) and group 2 (five patients) with serum ferritin levels below and above 1000 ng/mL, respectively. T2* MRI assessments were done for evaluation of hepatic and cardiac iron status. Group 1 and group 2 had mean serum ferritin levels of 817.300 ± 244.690 ng/mL and 1983.80 ± 662.862 ng/mL, respectively (P = .003). T2* MRI showed comparable moderate to severe hepatic iron overload status in both. None of the patients had myocardial iron deposition. We conclude that serum ferritin does not reflect the hepatic iron overload status in our patients with TI on regular transfusion.

4262 Background: Despite availability of iron chelation, iron-mediated cardiac toxicity remains the leading cause of death in thalassemia major patients. Although serum ferritin is widely used as a measure of iron overload, this has been challenged by recent magnetic resonance imaging (MRI) studies. Magnetic resonance using myocardial T2* is a highly sensitive, non-invasive and reproducible technique for detection of myocardial iron content. Materials and Methods: Seventy-four children are on follow-up at the Pediatric Thalassemia Day Care Center, Sultan Qaboos University Hospital, Muscat, Oman. Twenty-seven patients above the age of 7 years underwent T2* MRI procedure, and 9 of these patients had a follow-up T2* MRI at an interval of 1 year. MRI T2* was introduced at our institution in 2007 but was performed only on patients over the age of 12 years as it was thought that younger children would be unable to comply with the requirements of the MRI examination. Initially, we found that many of our patients failed to complete the procedure for T2* MRI (28.5% failure rate) mainly because of their inability to either hold their breath in expiration or due to movement during the procedure. But after training by physiotherapy we were successful in completing the procedure in children as young as 7 years, with no failures without the use of general anesthesia, as has been practiced by some centers. Results: Previous reports reveal no detectable cardiac iron in patients with thalassemia major less than 9.5 years of age. But we have detected in our patients severe and mild cardiac iron overload at the age of 7.5 years and 9.5 years respectively. At the time of the initial T2*MRI, the patient with severe cardiac iron overload was on chelation with Desferrioxamine with sub-optimal compliance, with a ferritin of 2605 ng/ml and a T2* MRI cardiac value of 9.3 ms. Repeat T2* MRI after 18 months (despite extensive counseling and optimization of chelation) revealed a cardiac T2* value of 4.8 ms at a ferritin level of 2796 ng/ml revealing that cardiac siderosis worsened despite the fairly constant ferritin level and the patient was shifted to combination chelation therapy. Also 44.5 % of our patients have moderate to severe hepatic iron overload. All these children were on regular 3–4 weekly follow-up for transfusion therapy with serial monitoring of ferritin levels guiding the chelation therapy. Of these, 62.9% (n=17) are on Deferiprone monotherapy at a mean dose 85.7 mg/kg, 33.3 % (n=9) are on combination chelation therapy with Deferiprone and Desferrioxamine, mean dose 95.6 mg/kg and 36.6 mg/kg respectively, and 14.2% (n=1) on Deferasirox at a dose of 40 mg/kg. Our results revealed inadequate iron chelation in some of our patients, most probably due to sub-optimal compliance that was not detected by serial ferritin monitoring (mean =1309 ng/ml). Moreover there was a poor correlation of ferritin to cardiac T2* and hepatic T2* values. Conclusions: With compliance to chelation therapy being a major issue in our patients, and failure of ferritin levels to predict the severity of cardiac and hepatic iron overload in some of the patients in a younger age group; we emphasize the importance of early and routine T2* MRI to detect organ iron overload for timely intervention with optimal iron chelation therapy in patients with thalassemia major. Disclosures: No relevant conflicts of interest to declare.

The role of erythropoiesis-stimulating agents (ESAs) in the management of chemotherapy-induced anemia (CIA) is becoming increasingly recognized in the field of medical oncology, with paucity of data in pediatrics. We evaluated the efficacy and tolerability of a single-dose darbepoetin alfa, a long-acting ESA, given to 35 pediatric acute lymphoblastic leukemia (ALL) children during induction chemotherapy. Compared to a retrospective control group, the studied patients have required significantly less units of packed red blood cells (0.88 units/patient in the studied group versus 2.04 units in controls), with no major side effects. We recommend further prospective double-blinded studies with more tailored dosing regimens in pediatric ALL cases and solid tumors.

Iron overload is mainly responsible for the morbidity and mortality in patients with beta thalassemia major (TM). Our aim was to compare treatment outcomes with oral iron chelators, deferiprone (DFP), and deferasirox (DFX) in the first two decades on therapy. Seventy patients with TM (mean age ± SD, 7.9 ± 4.2; range 1.5-17 years) attending the pediatric day care unit for regular transfusional support were enrolled in this cross-sectional cohort study. The patients were treated either with DFP at the dose of 75-100 mg/kg/d in three divided doses after food or DFX at the dose of 25-40 mg/kg/d as single dose before food. Mean serum ferritin (±SD) was lower in patients below 10 years (n = 44) at 1283 (±600) ng/mL when compared with patients ≥10 years (n = 19) at 1546 (±589) ng/mL. There was no significant difference in mean serum ferritin (±SD) level in patients receiving DFP (1360 ± 589) versus DFX (1260 ± 641) in this cohort, P > 0.05. 67% of the patients had Vitamin D deficiency (<50 umol/L). Our results show comparable efficacy of DFP and DFX with regards to iron chelation as estimated by serial serum ferritin levels; however, MRI T2* values were higher in the DFP-treated patients compared to DFX treatment.