Risks associated with oral deferiprone in the treatment of infratentorial superficial siderosis

Y Sammaraiee,J Porter,G Banerjee,P Eleftheriou,S Farmer,P Cowley,D J Werring,B Hylton

doi:10.1007/s00415-019-09577-6

Y Sammaraiee, J Porter + Show 6 more

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ObjectiveDeferiprone is an iron chelator that has recently been used to treat patients with infratentorial superficial siderosis (iSS). It is considered to have a generally favourable safety profile but concerns have been raised due to the risk of agranulocytosis. We aimed to evaluate the safety and tolerability of oral deferiprone as a treatment for patients with iSS.MethodsWe present a case series of 10 consecutive patients presenting with classical iSS treated with deferiprone.ResultsTen patients were followed up for a mean period of 2.3 years (range 0.5–5.5 years). Four patients (40%) were withdrawn from treatment because of treatment-related side effects. The reasons for treatment discontinuation were neutropenic sepsis (n = 3) and fatigue (n = 1). In 2 out of the 3 cases of neutropenic sepsis, patients initially developed neutropenia without sepsis. The mean time to neutropenic sepsis following deferiprone was 1.2 years (range 0.3–2.5) with mean neutrophil count of 0.4 (range 0.3–0.5). Six patients (60%) reported no change in neurological function while on treatment, and four patients (40%) reported that their condition deteriorated.ConclusionsDeferiprone was poorly tolerated, with 40% of patients withdrawing from treatment, most commonly due to neutropenic sepsis, after an average of 2 years on treatment. This study increases the number of reported cases of agranulocytosis in patients with iSS treated with deferiprone. Clinicians treating iSS patients with deferiprone should be aware that this drug has a potentially life-threatening side effect of neutropenic sepsis, and should ensure that appropriate haematological monitoring is in place.

Highlights

Central nervous system (CNS) infratentorial superficial siderosis is a rare but disabling neurological condition that results from hemosiderin deposition on the pial surface of the brain and spinal cord [1]
A dural defect associated with neurosurgery or trauma was present in five patients and CNS tumour/cyst was present in three patients
On the latest yearly follow-up scans, 8 patients had scans available, all of which showed no significant change in siderosis burden following treatment. In this case series of patients with infratentorial superficial siderosis, deferiprone was poorly tolerated, with 40% of patients withdrawing from treatment, most commonly due to neutropenic sepsis after an average of 2 years on treatment

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Introduction

Central nervous system (CNS) infratentorial superficial siderosis (iSS) is a rare but disabling neurological condition that results from hemosiderin deposition on the pial surface of the brain and spinal cord [1]. Iron chelation therapy with deferiprone (initially developed for treatment of thalassaemia), which readily crosses the blood brain barrier, has been used to treat patients with iSS but its efficacy remains unproven [2, 5]. Deferiprone is considered to have a generally favourable safety profile [2], but concerns have been raised because of a single case report of agranulocytosis [6]. It is currently not known whether this risk is greater in patients without systemic iron overload, such as those with iSS, than in patients with transfusional iron overload where the risk is about 1% [7]

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