Retrospective Survey of Iron Overload Prevalence & Chelation Practices in Transfusion-Dependent Myelodysplastic Syndromes in a West Kent District General Hospital, SE England.
Authors: Jeyabalasingam Hajane , Kamat Anil Vaikunth , Shafi Tariq , Ezekwesili Raphael A. 
Published: October 2019

Abstract
Abstract 4857

Background
The incidence of myelodysplastic syndromes is about 9 -10 / 250000 population. Iron overload is increasingly recognised as a factor contributing to increased morbidity & mortality in transfusion-dependent myelodysplastic syndromes. Transfusion dependency, a variable in WHO based Prognostic Scoring System ( WPSS), is associated with reduced overall survival. However iron chelation uptake remains poor. Lack of robust data on prevalence of iron overload & absence of randomised controlled trials showing efficacy of iron chelation in improving overall survival & patient outcome complicates clinical management as well as resource planning to provide for iron chelation therapy.

Methods
This retrospective survey was conducted to assess the red cell transfusion dependency, iron overload prevalence, iron chelation practices in a District General Hospital based in West Kent, SE England covering a population of 250000.The data was collected from clinical, laboratory & blood bank records.

Results
Between Jan – Dec 2008, of 129 patients transfused ; MDS 27 ( M 12/ F 15), age range 57 -89 years, FAB subtypes :RA( n= 1) RARS( 3 )RCMD (4 )RAEB-1( 2)MDS transformed to AML (3)MPD/MDS ( 4 )NOS ( 5 ) Secondary MDS (4) Del 5q (1); IPSS score : 0 (n= 16), 0.5 ( 5), 1 ( 1), 1.5 ( 1 ), 2 ( 1), 2.5 ( 1) 3.5 ( 2);WHO score : 0 ( n= 13), 1 ( 3), 2 ( 1), 3 ( 1 ), 9 deaths in this cohort. Red cell transfusions/patient range was 2 – 66 units( median 12 ), baseline ferritin 4.4 – 2406.9 ug/l( median 969.7), last ferritin 30.8 – 5580.6 ug/l( median 969.7).
Based on eligibility criteria for iron chelation being ferritin > 1000 ug/l & expected survival > 1 year, 12 patients were eligible of which 4 (33%)were on therapy ( n= 3 on Desferrioxamine ( SC ( 1), intermittent IV ( 2) ), 1 on Deferasirox ( previous intolerance to Desferrioxamine). Of 12 eligible, 3 had renal impairment ( eGFR < 60 ml/min). Of 4 chelated patients, age range was 66 – 87, last Ferritin 1007.2 – 5580.6 ug//l, IPSS 0 – 0.5, red cell transfusions/patient 29 – 66 units, FAB subtypes : RA( 1)RARS (2) Secondary MDS (1).
There were 9 deaths ( n= 1 on chelation) in this cohort with age range 62 -89 years IPSS 0 – 3.5, FAB subtypes at diagnosis :RARS( 1)RCMD( 2 ) MDS transformed to AML ( 2 ) MPD/MDS (1) NOS ( 1)Secondary MDS (1) Del 5q ( 1); last ferritin 574.1 – 3719.3 ug/l. Contributing causes of deaths other than MDS included : Neutropenic sepsis ( 1) IHD/ CCF (2) Carcinoma prostate (1) Transformed AML (4) Pneumonia (1) COPD (1) NHL (1).

Conclusion
The survey confirms poor iron chelation uptake. This could be due to varied reasons such as patient or physician preferences, clinical awareness & availability of resources. Adequate resource planning is needed to improve iron chelation practices along with tools to aid clinical decision making process such as a computerised prompt to consider iron chelation based on IPSS, predicted survival, red cell transfusion dependency & ferritin level. A longitudinal prospective survey will also help clarify the cost effectiveness of this intervention as well as provide useful quality of life, patient outcome & overall survival data.

Disclosures
No relevant conflicts of interest to declare.