A Prospective Observational Multicenter Study on Deferiprone & Deferasirox in Clinical Practice of Pediatric Patients with Transfusion-Dependent B-Thalassemia

Abstract

Background: Iron overload is inevitable but a manageable complication of frequent blood transfusion, the effectiveness and safety of two iron chelation therapy in young children with transfusion-dependent B thalassemia (TDB-T) using either deferiprone (DFP) or deferasirox (DFX) were well studied in clinical trials. The primary objectives were; reporting efficacy and frequency of all adverse events (AEs) as compared with published data. Secondary objective was reporting deviation from guidelines, The analysis of clinical data is the first step to design new strategies Methodology: An investigator initiated 2-year multicenter prospective study enrolling over 6 months period; 302 children with TDB-T from 11 centers; keeping pre-transfusion Hb >8gm/dl. When serum ferritin (SF) reached around 1000 ng/ml; they had received according to availability; either DFP liquid solution in a dose; 75 mg/kg/day (n=62) or DFX (n=240); (dispersed tablet; 25% or film-coated tablet 75% in a dose; 20-25 mg/kg/d or its equivalent). CBC was done biweekly in DFP and pre-transfusion in DFX group. Liver transaminases, serum creatinine and (SF) were done /3 months. Changes in growth velocity over time were documented. Results: 66% were males, age at enrolment was; (11-19 and 14-26 months) in DFP and DFX respectively; they had received (6-8) and (7-11) transfusions prior to chelation in both groups respectively in addition to (16-21) during the study. 20% of patients did not achieve the target pre-transfusion Hb level. At initiation of DFP; SF median; 960 (IQR; 122 ng/ml) while those on DFX had SF; median 1070 (IQR 138 ng/ml) both groups had comparable transfusion iron input during the study. At 24 months of regular transfusion-chelation; SF < 1000 ng/ml was noticed in 65% and 60% of the patients respectively with good growth velocity in children using either chelator. Unnecessary over-dosing of DFX > 40 mg/kg was observed in 5%, meanwhile 3.2% had received DFP in a dose >75-100 mg/kg while SF was <1500 ng/ml. Under-reporting of adverse events in both groups was observed; 5% GIT upset, neither arthralgia nor agranulocytosis, neutropenia (3.2%) in DFP group and CBC was not checked biweekly; but only prior to transfusion. 4-5 % had elevated transaminases in both chelators, while patients on DFX reported; GIT upset in 4.2% and rash in 1.6%. Elevated serum creatinine > 33% from baseline on 2 successive visits was observed in 5% in DFX without reducing the dose or re-check. No unexpected, serious severe adverse events were reported in both groups. Poorly controlled patients with SF > 1500 ng /ml at 12 or 24 months were 12, 8% in DFP group; in contrast to 15%, 10% in DFX group respectively; with no statistical difference; (compliance was comparable). The total DFP and DFX discontinuation ratio was 5% in each group. Conclusion: infants and young children with TDB-T naïve to chelation were put on mono-therapy at younger age than reported before. Both chelators were effective, well tolerated and with no severe safety concerns; however deviation from guidelines was observed as; unnecessary over-dosing of DFX and under-reporting of AEs in both groups in real life practice. Disclosures Hamdy: ApoPharma: Honoraria; Amgen: Honoraria; Bayer: Honoraria; Novartis: Honoraria; NovoNordisk: Honoraria; Roche: Honoraria; Takeda: Honoraria.