Serum Ferritin, Labile Plasma Iron and Transferrin Saturation: Comparison Between Underlying Anemias with Transfusional Iron Overload Before and After Treatment with Deferasirox.
Authors: Porter John B , Elalfy Mohsen , Viprakasit Vip , Giraudier Stephane , Chan Lee Lee , Lai Yongrong , El-Ali Ali , Martin Nicolas , Cappellini M Domenica 
Published: October 2019

Abstract
Abstract 2126

Background:
In patients with transfusion-dependent anemias, monitoring the efficacy of iron chelation therapy (ICT) using serum ferritin (SF) alone can sometimes be challenging; therefore, additional serum markers would be helpful. Furthermore, any differences between different anemias for the relationship between SF and other serum markers both before and in response to ICT may be useful to predict relative risk of iron-mediated toxicity between these conditions. Data from the 1-yr EPIC (Evaluation of Patients' Iron Chelation with Exjade®) trial allows assessment of iron parameters in a large cohort of patients with thalassemia, myelodysplastic syndromes (MDS) and sickle cell disease (SCD). Here we evaluate trends in liver iron concentration (LIC), transferrin saturation (TfSat) and labile plasma iron (LPI) in their relation to SF levels and assess systematic differences between underlying anemias. Relationships were assessed at baseline (BL), reflecting iron accumulation at study entry, and also at end of study (EOS), with changes reflecting iron excretion after 1 yr treatment with deferasirox.

Methods:
LIC, TfSat and LPI were measured at BL and at EOS for each underlying disease. Changes in these parameters as well as relationships between these parameters and SF were assessed by SF categories at BL and at EOS. For EOS measurements, last observation carried forward was used for all parameters (last post-BL available value), except for LPI, for which 1-yr visit was used. Pre-deferasirox dose LPI levels are reported.

Results:
Data from 1114 thalassemia patients, 336 MDS patients and 80 SCD patients were available for analysis. For all underlying anemias, LIC was higher at higher SF categories; in thalassemia patients for eg, with BL SF categories <1000, 1000–2000, 2000–3000, 3000–4000, 4000–5000, >5000 ng/mL, the mean LIC values at BL were 4.9, 9.0, 15.3, 22.1, 27.2, 32.5 mg Fe/g dw, respectively.
Overall, mean TfSat was 89.6% (n=755) in thalassemia patients at BL and 96.1% (n=955) at EOS, compared with 82.5% (n=116) and 83.8% (n=171) in MDS patients, respectively. In SCD patients, TfSat was 61.3% (n=71) at BL and 64.1% (n=74) at EOS. TfSat was lowest in SCD patients across the full range of SF categories examined (Figure). At BL, TfSat was higher at higher SF categories in all diseases, with a similar trend at EOS, although at EOS this trend was more evident in MDS and SCD (Figure).
Overall, mean LPI levels at BL and EOS were 1.25 μmol/L (n=472) and 0.59 μmol/L (n=818) in thalassemia patients, 0.53 μmol/L (n=221) and 0.14 μmol/L (n=147) in MDS patients, and 0.11 μmol/L (n=55) and 0.10 μmol/L (n=46) in SCD patients, respectively. LPI levels were highest in patients with thalassemia and lowest in SCD patients across SF categories (Figure). After 1 yr treatment with deferasirox, LPI levels were reduced in thalassemia and MDS patients, but there was no difference in patients with SCD. LPI was higher at higher SF categories in MDS patients at both BL and EOS, with a similar trend in SCD patients at EOS, although there was little relationship in thalassemia patients (Figure).

Discussion:
At matched SF levels and across a wide range of SF values, TfSat was lower in SCD patients, in comparison to thalassemia and MDS patients, both at BL and EOS. Similar observations have been reported previously and may contribute to the lower propensity for extra-hepatic iron accumulation in SCD patients. The mechanisms for this difference remain unclear, but could be attributed to sequestering of iron due to chronic inflammation in SCD. TfSat did not appear to decrease after 1 yr treatment with deferasirox, in any underlying anemia. The relationship of LPI to SF categories differed between underlying anemias; both at BL and EOS. At BL, SCD patients had low LPI values across the full range of measured SF values, whereas higher LPI levels at higher SF categories were most evident in MDS patients. Overall, LPI was highest in thalassemia patients. After 1 yr treatment with deferasirox, LPI was decreased in thalassemia and to a lesser extent in MDS patients, but there was no change from the low level at BL in SCD patients. The decrease in LPI in MDS and thalassemia at EOS may reflect the effects of residual plasma chelator 1 day after the previous dose and/or the decrease in storage iron over 1 yr of treatment. With further evaluation, LPI could become a useful marker of iron overload and chelation response in patients with MDS and possibly thalassemia.

Disclosures:
Porter: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Viprakasit:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. El-Ali:Novartis: Employment. Martin:Novartis: Employment. Cappellini:Novartis: Speakers Bureau.