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2146 Different Thresholds of Serum Ferritin Levels for Prediction of Liver Iron Concentration in HemoglobinopathiesClinically Relevant Abstract

Regulation of Iron Metabolism
Program: Oral and Poster Abstracts
Session: 102. Regulation of Iron Metabolism: Poster II
Sunday, December 6, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Angela Vitrano1*, Giuseppina Calvaruso1*, Lorenzo Tesè2*, Francesco Gioia2*, Filippo Cassarà1*, Saveria Campisi3*, Franco Butera3*, Valeria Commendatore3*, Michele Rizzo, MD4*, Vincenzo Santoro5*, Valeria Cigna6*, Alessandra Quota7*, Sabrina Bagnato8*, Crocetta Argento9*, Carmelo Fidone10*, Dario Schembari10*, Calogera Gerardi11*, Filippo Barbiera11*, Giuseppe Bellissima12*, Giovanni Giugno12*, Gesualdo Polizzi13*, Rosamaria Rosso14*, Giovanna Abbate15*, Vincenzo Caruso, MD16*, Elisabetta Chiodi17*, Maria Rita Gamberini18*, Benedetta Giorgi19*, Maria Caterina Putti, MD19*, Maria Rosaria De Ritis20*, Aldo Filosa, MD21*, Esther Natalie Oliva, Doctor22, Nicola Arcadi23*, Massimiliano Sacco1*, Rosario Di Maggio1*, Laura Mistretta1*, Veronica Di Salvo1*, Antonino Giangreco1* and Aurelio Maggio1

1Campus of Haematology Franco e Piera Cutino- A.O.O.R. “Villa Sofia-Cervello”, Palermo, Italy
2UO of Radiology, Campus of Haematology Franco e Piera Cutino- A.O.O.R. “Villa Sofia-Cervello”, Palermo, Italy
3Ospedale Umberto I, Siracusa, Italy
4Section of Hematology, A.O. Sant'Elia, Caltanissetta, Italy
5Ospedale S. Elia, Caltanissetta, Italy
6Centro Spoke Talassemia, Gela (CL), Italy
7Centro Microcitemia, A.O., Gela (CL), Italy
8Centro Microcitemia, A.O. "V. Emanuele III", Gela (CL), Italy
9U.O.S. di Talassemia, Ospedale San Giovanni di Dio, Agrigento, Italy
10A.O.‘‘M. Paternò Arezzo’’, Ragusa, Italy
11A.O.O.C.R., Sciacca, Italy
12ASP CT, P.O., Caltagirone, Italy
13Ospedale Vittorio Emanuele, Catania, Italy
14U.O. Talassemie ed Emoglobinopatie, Ospedale, Catania, Italy
15U.O. Talassemia Ospedale Garibaldi, Catania, Italy
16Garibaldi Hospital, Catania, Italy
17Servizio Radiologia Ospedaliera-Universitaria, Arcispedale “S.Anna”, Ferrara, Italy
18Pediatria, Adolescentologia e Talassemia, Arcispedale “S.Anna”, Ferrara, Italy
19A.O di Padova, Padova, Italy
20UOD Malattie rare del globulo rosso, AORN "A. Cardarelli", Napoli, Italy
21UOD Malattie rare del globulo rosso, AORN, Napoli, Italy
22A.O. Bianchi-Melacrino-Morelli, Haematology, Reggio Calabria, Italy
23A.O. Bianchi-Melacrino-Morelli, Hematology, Reggio Calabria, Italy

Introduction. This was a cross-sectional study of patients with hemoglobinopathies attending 13 Italian centers participating in the LICNET (Liver Iron Cutino Network) network promoted from Piera Cutino partnership  and instituted by our center (Campus of Haematology Franco e Piera Cutino- A.O.O.R. Villa Sofia Cervello, Italy) on February 2013. LICNET is addressed to the diagnostics of iron overload in liver by R2 MRI (Ferriscan®) in patients with hemoglobinopathies.  Ferriscan is a rapid scan method now available (10 minutes). This tool is crucial to have accurate and reliable measures for iron body burden control in hemoglobinopathies.

Methods. Data included patients with β-thalassemia major (TM) (regularly transfused) (TX), β-thalassemia intermedia (TI) (both TX and non-transfused) (non-TX), and sickle cell disease (SCD) (both TX and non-TX). The main aim of the study was to evaluate how serum ferritin levels (SFLs) predict liver iron concentration (LIC) in different hemoglobinopathies, and to have valuable information about prognosis and response to therapy. In particular, to identify SFLs that best predict LIC thresholds of clinical significance (7 and 15 mg Fe/g dw) by identifying levels with highest sum of sensitivity and specificity was used the receiver operating characteristic (ROC) curve analysis.

Results. A total of 363 patients were evaluated in this analysis, with a mean age of 35.6 ± 13.0 years (range: 6-76) and including 160 (44.1%) males. The underlying diagnosis were β-TM (n=204, 56.2), β-TI (n=102, 28.1%), and SCD (n=57, 15.7%). Among β-TI patients, 60 (58.8%) were on transfusion therapy. Similarly, in patients with SCD 34 (59.6%) were on transfusion therapy. The mean LIC in the study population was 7.8 ± 9.6 mg Fe/g dw and the median was 4.0 mg Fe/g dw.

Across underlying diseases, LIC distribution was as follows: β-TM (mean: 9.0 ± 10.7, median: 4.9 mg Fe/g dw), TX β-TI (mean: 7.1 ± 7.3, median: 5.0 mg Fe/g dw), non-TX β-TI (mean: 5.1 ± 6.0, median: 3.2 mg Fe/g dw), TX SCD (mean: 8.5 ± 11.0, median: 4.5 mg Fe/g dw), and non-TX SCD (mean: 3.1 ± 1.9, median: 2.4 mg Fe/ g dw). It was apparent that TX patients irrespective of underlying diagnosis have a comparable proportion of patients with high LIC risk categories (>7 mg Fe/g dw) (p=0.627).

Among chelated patients, LIC distribution was as follows: Deferoxamine (DFO) (mean: 7.3 ± 8.5, median: 4.7 mg Fe/g dw), Deferiprone (DFP) (mean: 11.6 ± 11.4, median: 8.4 mg Fe/g dw), Deferasirox (DFX) (mean: 7.8 ± 10.3, median: 3.2 mg Fe/g dw), DFO+DFP (mean: 8.2 ± 10.6, median: 4.5 mg/ Fe g dw), and other combinations (mean: 6.5 ± 4.0, median: 5.1 mg Fe/ g dw), with a statistically significant difference noted between groups (p=0.009) with the highest median among chelated patients noted in DFP treated patients and lowest median noted in DFX treated patients.

For underlying disease groups, ROC curve analysis showed that SFLs that best predict LIC thresholds of 7 and 15 mg Fe/g dw varied, although patients with β-TI showed lowest SFLs to predict these thresholds especially non-TX patients (Fig. 1, Fig.2).

Discussion. This study suggest as high values of LIC are present even in patients with TI or SCD, confirming that gastro-intestinal iron absorption is one of the main mechanism for secondary iron overloading. Moreover, close to 20% of patients with non-TX β-TI continue to have high LIC thresholds, while none of non-TX patients with SCD have LIC values > 7 mg Fe/g dw. The evidence that SFLs of 900 ng/mL are related in β-TI with LIC > 15 mg Fe/g dw (Fig. 2) suggests as chelation treatment could be reconsidered earlier in this cohort of patients. Finally, these findings suggest as LIC is predicted by different SFLs according to the different types of hemoglobinopathy.

Figure 1. Receiver operating characteristic curve analysis of serum ferritin level for predicting LIC>7 mg Fe/g dw in Thalassemia Major, Thalassemia Intermedia and Sickle Cell Disease patients.

Figure 2. Receiver operating characteristic curve analysis of serum ferritin levels for predicting LIC>15 mg Fe/g dw in Thalassemia Major, Thalassemia Intermedia and Sickle Cell Disease patients.

 

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH