Efficacy and safety of early-start deferiprone in infants and young children with transfusion-dependent beta thalassemia: Evidence for iron shuttling to transferrin in a randomized, double-blind, placebo-controlled, clinical trial (START).

Children with transfusion-dependent thalassemia (TDT) require regular blood transfusions that, without iron-chelation therapy, lead to iron-overload toxicities. Current practice delays chelation therapy (late-start) until reaching iron overload (serum ferritin ≥1000 µg/L) to minimize risks of iron-depletion. Deferiprone's distinct pharmacological properties, including iron-shuttling to transferrin, may reduce risks of iron depletion during mild-to-moderate iron loads and iron overload/toxicity in children with TDT. The early-start deferiprone (START) study evaluated the efficacy/safety of early-start deferiprone in infants/young children with TDT. Sixty-four infants/children recently diagnosed with beta-thalassemia and serum ferritin (SF) between 200 and 600 µg/L were randomly assigned 1:1 to receive deferiprone or placebo for 12 months or until reaching SF-threshold (≥1000 µg/L at two consecutive visits). Deferiprone was initiated at 25 mg/kg/day and increased to 50 mg/kg/day; some recipients' dosages increased to 75 mg/kg/day based on iron levels. The primary endpoint was the proportion of patients ≥SF-threshold by month 12. Monthly transferrin saturation (TSAT) assessment evaluated iron-shuttling. At baseline, there was no significant difference in mean age (deferiprone: 3.03 years, placebo: 2.63 years), SF (deferiprone: 513.8 µg/L, placebo: 451.7 µg/L), or TSAT (deferiprone: 47.98%, placebo: 43.43%) between groups. At month 12, there was no significant difference in growth or adverse event (AE) rates between groups. No deferiprone-treated patients were iron-depleted. At month 12, 66% of patients receiving deferiprone remained below SF threshold versus 39% of placebo (p = .045). Deferiprone-treated patients showed higher TSAT levels and reached ≥60% TSAT threshold faster. Early-start deferiprone was well-tolerated, not associated with iron depletion, and efficacious in reducing iron overload in infants/children with TDT. TSAT results provide the first clinical evidence of deferiprone shuttling iron to transferrin.

Deferiprone vs deferoxamine for transfusional iron overload in SCD and other anemias: a randomized, open-label noninferiority study.

Many people with sickle cell disease (SCD) or other anemias require chronic blood transfusions, which often causes iron overload that requires chelation therapy. The iron chelator deferiprone is frequently used in individuals with thalassemia syndromes, but data in patients with SCD are limited. This open-label study assessed the efficacy and safety of deferiprone in patients with SCD or other anemias receiving chronic transfusion therapy. A total of 228 patients (mean age: 16.9 [range, 3-59] years; 46.9% female) were randomized to receive either oral deferiprone (n = 152) or subcutaneous deferoxamine (n = 76). The primary endpoint was change from baseline at 12 months in liver iron concentration (LIC), assessed by R2* magnetic resonance imaging (MRI). The least squares mean (standard error) change in LIC was -4.04 (0.48) mg/g dry weight for deferiprone vs -4.45 (0.57) mg/g dry weight for deferoxamine, with noninferiority of deferiprone to deferoxamine demonstrated by analysis of covariance (least squares mean difference 0.40 [0.56]; 96.01% confidence interval, -0.76 to 1.57). Noninferiority of deferiprone was also shown for both cardiac T2* MRI and serum ferritin. Rates of overall adverse events (AEs), treatment-related AEs, serious AEs, and AEs leading to withdrawal did not differ significantly between the groups. AEs related to deferiprone treatment included abdominal pain (17.1% of patients), vomiting (14.5%), pyrexia (9.2%), increased alanine transferase (9.2%) and aspartate transferase levels (9.2%), neutropenia (2.6%), and agranulocytosis (0.7%). The efficacy and safety profiles of deferiprone were acceptable and consistent with those seen in patients with transfusion-dependent thalassemia. This trial study was registered at www://clinicaltrials.gov as #NCT02041299.

Reticulocyte Hemoglobin Content (Ret He): A Simple Tool for Evaluation of Iron Status in Childhood Cancer.

BACKGROUND: Cancer-related anemia is a common complication of cancer and its treatment that may be mediated by nutritional deficiency or inflammatory cytokines inhibiting erythropoiesis. AIM: We evaluated the value of reticulocyte hemoglobin content (Ret He) as a marker of iron availability for erythropoiesis in childhood cancer and the impact of oral iron supplementation on hematologic parameters in patients with low Ret He. MATERIALS AND METHODS: This prospective study included 100 pediatric patients with cancer on chemotherapy who were screened for the presence of anemia. Patients with anemia underwent testing for complete blood count including Ret He on Sysmex XE 2100 and assessment of reticulocyte count, serum iron, serum ferritin, transferrin saturation, total iron-binding capacity, and C-reactive protein. Patients were classified according to their level of Ret He into normal or low Ret He using a cutoff level of 28 pg. Patients with low Ret He were subjected to 6 weeks' treatment with oral ion and were followed up with complete blood count and iron profile. RESULTS: Thirty-one (77.5%) patients had normal Ret He, and 9 (22.5%) had low Ret He. Ret He was positively correlated with red cell indices, but not with iron parameters. After oral iron supplementation, a significant increase in hemoglobin, reticulocyte count, and iron was found. CONCLUSIONS: We suggest that Ret He could be used as an easy and affordable tool for the assessment of iron deficiency anemia in childhood cancer during chemotherapy treatment. A trial of oral iron in patients with low Ret He may be useful to correct the associated anemia.