Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders

Abstract

New measures of iron accumulation in liver and heart (superconducting quantum inference device and magnetic resonance imaging), and oral iron chelators (deferiprone and deferasirox) are available for managing iron overload in thalassemia major. To assure appropriate use of these new health technologies, the Italian Society of Hematology appointed a panel of experts to produce clinical practiceguidelines for the management of iron overload in thalassemia major and related disorders. The analytical hierarchy process, a technique for multicriteria decision analysis, was applied to relevant key questions in order to identify the alternative strategies, generate explicit criteria for their evaluation, and check how well the alternatives fulfilled the criteria. The result of a comprehensive systematic review of articles released from 1990 to 2007 was used as a source of scientific evidence to compare the decisional options pairwise, and select the final recommendation. Every step in the model was developed from questionnaires and group discussion. The resulting recommendations advise about which examination to carry out in order to plan iron chelation therapy, when to start iron chelation, which iron chelator to choose in regularly transfused patients, how to monitor iron chelation therapy, and when and how to switch standard therapy.

Deferiprone (GPO‐L‐ONE®) monotherapy reduces iron overload in transfusion‐dependent thalassemias: 1‐year results from a multicenter prospective, single arm, open label, dose escalating phase III pediatric study (GPO‐L‐ONE; A001) from Thailand

“…Furthermore our findings that SF values were more likely to decrease in those patients who began with the highest SF values and lower iron intake from lower transfusion rate (<0.25 mg/kg/day in our study) are consistent with previous individual studies [42][43][44] and review of trends from several studies [38]. Also in the view of without a strong evidence to suggest that deferiprone has superior efficacy than desferoxamine, together with its associated adverse effects, some can be fatal, deferiprone remains the second line therapy for thalassemia major patients whose desferoxamine is inadequate or contraindicated as reviewed [45,46] and documented in all clinical practice guidelines around the world [47][48][49] including the latest registration filed by the US-FDA [50]. In this regard, our study has further confirmed that efficacy of deferiprone monotherapy is rather limited and should not be used as a first-line treatment in patients with transfusion-dependent thalassemia including severe Hb E/b thalassemia.…”

Reproducibility of liver iron concentration measured on a biopsy sample: A validation study in vivo

“…However, any validation study of a diagnostic quantitative procedure must report a determination coefficient (R 2 ) with a prediction interval. Above all, in this specific case, the 95% prediction interval would be reasonably narrow not extending over the identified threshold for iron concentration tissue damage and death [1,12]. However, regression analysis of the entire samples confirms the incomplete adequacy of small samples (i.e., <1 mg dw).…”

“…Determination of liver iron concentration (LIC) is essential to predict iron related tissue damage and disease and to guide chelation therapy [1]. Nowadays, only two validated noninvasive methods are available (MRI-R2 and R2*) [2] and liver biopsy continues to be the gold standard for hepatic iron determination.…”

Pretransplant serum ferritin level may be a predictive marker for outcomes in patients having undergone allogeneic hematopoietic stem cell transplantation

“…Therefore, albumin, which is a negative acute phase reactant, was included in the analysis [28,29] and there was no statistical significance between ferritin groups. However, serum ferritin level remains the most cost-effective, inexpensive and noninvasive measure for iron overload available worldwide [30,31]. It is important to estimate the significance of iron overload in patients who underwent alloHSCT using non-invasive imaging like liverspecific MRI.…”