Oral Chelator Deferiprone in Adult with Sickle Cell Disease.
Authors: Nzouakou Ruben , Habibi Anoosha , Lee Ketty , Luciani Alain , Deux Jean-François , Galacteros Frederic , Bachir Dora 
Published: October 2019

Abstract
Abstract 4615

INTRODUCTION
Long-term blood transfusion is essential for patients with sickle cell disease (SCD) in case of cerebral vasculopathy, organ dysfunction, leg ulcer, failure or intolerance of hydroxyurea treatment. Secondary iron overload is a factor of morbidity and mortality by organ damage.
In practice, three chelators are available: deferoxamine (DFO) which is administrated by subcutaneous infusion and therefore source of poor compliance in SCD. Deferasirox (DFX), the new oral chelator is the first line therapy since 2007. Deferiprone (DFP) is an option when DFX or DFO are contraindicated or inadequate. However, DFP has no approval for SCD.
The purpose of this study is to describe the characteristics of SCD patients treated by DFP.

METHODOLOGY
The patients included in this study arise from the group of the patients with long-term blood transfusion by manual exchange in Henri Mondor's SCD center, and in whom iron overload is treated by DFP.
The monitoring of iron overload is obtained by regular serum ferritin level, combined liver and heart MRI. Only one iron measure by MRI is available for each patient throughout the study.

RESULTS
Nine patients (8 SS and 1 Sβ0thal) are included: 5 men and 4 women. The mean age is 44.2 years (22 to 64 years). The median duration of chronic transfusion is 10 years (4 to 27 years). The average dose of DFP is 68 mg / kg / day (50 to 93 mg / kg / day). The median follow-up under DFP is 30 months (7 to 60 months). The median level of serum ferritin before the initiation of DFP is 5830 μg / l (1800 to 9300 μg / l); and the median level of serum ferritin at the end point is 7940 μg / l (4540 to 11300 μg / l). MRI shows an important hepatic iron overload (up to 320 μmol) in all patients and one cardiac iron overload (T2* = 12 ms).
Three patients stopped DFP and switch to deferasirox (DFX) as soon as DFX was available. For the other patients, the reason of prescribing DFP instead of DFX was renal failure in 5 patients and DFX related GI symptoms in one patient.
No agranulocytosis is observed. The weekly then monthly monitoring of blood count is insured for all patients. No cytolysis by drug's toxicity is observed, except for one patient with liver transplant and who has an active HCV infection.

DISCUSSION
Serum ferritin level is the easiest marker of iron overload follow-up, but is subject of important variations due to inflammation, hemolysis, and cytolysis. Indeed, MRI is the only one reliable measure.
The evidence of cardiac iron overload is proved in one patient, and confirms the importance of this measure on SCD patients. This motivates the edition of guidelines concerning the prevention and monitoring of iron overload among these patients.
The dosage of DFP remains reasonable compared to the mean dosage use in other pathologies. This dosage depends of the degree of iron overload and the individual tolerance.
Data are not sufficient at these days to evaluate the efficacy of DFP to reduce or to stabilize the level of iron overload. However, we observe globally a good clinical and biological tolerance, even in patients who have organ transplant and therefore have several concomitant treatments.

CONCLUSION
DFP in patients with SCD is globally well-tolerated, but its efficiency is not proved yet. Approval of DFP for SCD is needed. As life expectancy improves in SCD, more patients will require long-term transfusion and thus iron chelation therapy. Cardiac Iron overload is possible in patients with SCD. So, it would be systematically looked after.

Disclosures:
No relevant conflicts of interest to declare.