Longitudinal Changes in Iron Overload Parameters and Iron Chelation Therapy in Young Patients with Thalassemia Major,

Abstract

Abstract 3202 Background:New modalities for the assessment of iron overload and the availability of new oral chelators have led to important changes in the iron load status and its treatment for patients with thalassemia major (TM). The goals of this retrospective analysis were to evaluate the changes that occurred in regards to the degree of iron overload, as well as to the therapeutic regimen of iron chelation over the last decade in young patients with TM. Methods:All patients with TM followed in our unit, who were <18 years at certain time points, were included in this study. Group A included all patients who were younger than 18 years old on 1/1/2001, while group B, C, D, E and F on 1/1/2003, 1/1/2005, 1/1/2007, 1/1/2009, and 1/1/2011, respectively. Liver iron concentration (LIC) and cardiac siderosis (T2*) were evaluated by MRI. Cardiac iron concentration (CIC) was calculated based on the recently prescribed formula CIC= 45 × (T2*Heart)−1.22.The closest MRI, which was <12 months from the time point, was recorded for each patient at each group. The therapeutic regimen for iron chelation, being deferoxamine (DFO), deferiprone (DFP), combination therapy of DFO and DFP (DFO+DFP) and deferasirox (DFX), used at the different time points were also recorded. Results:The results of the analysis are shown in the following table:GroupABCDEFN1109282725648Mean age (SD) in years12.24 (4.8)11.93 (5.2)11.36 (5.3)11.87 (5.2)11.29 (4.4)11.74 (4.3)Mean ferritin (SD) (μg/L)1981 (1364)1767 (1346)1720 (1402)1909 (1422)1567 (1670)1740 (1502)MRI (N)011221177Mean LIC (SD) (mgFe/g.d.w.)7.4510.57 (8.33)3.68 (4.55)2.30 (4.53)3.9 (3.06)Mean CardiacT2* (SD) (msec)28.130.4 (4.53)29.9 (7.15)34.5 (5.73)33.3 (1.63)Mean CIC (SD) (mgFe/g.d.w.)0.770.74 (0.42)0.71 (0.37)0.63 (0.25)0.63 (1.54)DFO (%)10089.1354.7616.278.823.57DFP (%)02.1711.9011.6235.2921.42DFO+DFP (%)08.697.149.3007.14DFX (%)0026.1862.7955.8867.85N= numberFerritin levels did not change significantly over the last decade (p>0.05). There was a trend for decreasing values of LIC (Independent Samples Kruskal-Wallis test, p=0.075) with the mean LIC of group E and F being significantly lower than group C (Mann-Whitney test, p<0.05). Similarly, there was a trend for improvement in the indexes of cardiac iron load. Of note is, that cardiac overload was not documented in this group of patients. None of the patients has significant (T2*<10 msec), and only 3 patients had moderate cardiac siderosis (T2*>10 <20 msec). Conclusions:A steady decrease in the number of young patient with thalassemia has been observed, reflecting the efficacy of the thalassemia prevention program. As expected, the utilization of MRI to evaluate iron overload has increased significantly especially in the second part of the last decade, but it remains limited mainly to older children and teenagers. Oral chelation has become the preferable mode of treatment of hemosiderosis in young patients with TM. While DFX is, currently, the most used iron chelator, the use of DFO is becoming limited as an additive therapy to DFP. Despite presumed better compliance with oral chelation therapy, the iron overload indexes have not improved dramatically. This may reflect the short period of using the oral chelators or/and the need for further treatment intensification. Disclosures:Kattamis:Novartis Oncology: Honoraria, Research Funding, Speakers Bureau; Apopharma: Honoraria.