Long Term Comparative Studies in Thalassemia Patients Treated with Deferoxamine or a Deferoxamine/Deferiprone Combination. Identification of Effective Chelation Therapy Protocols

Abstract

For the past 2-6 years, two groups of thalassemia patients, one of 16 patients on deferoxamine (DFO) monotherapy (35-80 mg/kg, 2-5 days/week) and the other group comprising 19 patients on a deferiprone (L1) and DFO combination therapy (L1 75-100 mg/kg/day and DFO 30-60 mg/kg, 1-5 days/week), have been studied and compared before and after the introduction of the combination therapy. The patients on the combination therapy were mainly those not complying or experiencing toxicity with DFO. The effects of chelation therapy on iron load was monitored using regular serum ferritin measurements and also magnetic resonance imaging (MRI) T2* relaxation time measurements at the end of the study. In both groups, cardiac MRI T2* levels were within the normal range (>19 ms) in more than 75% of the patients. There was a substantial improvement in serum ferritin levels and normalization of the MRI T2* levels of the liver in many cases treated with the combination therapy at effective doses by comparison to the DFO group, where the serum ferritin and MRI T2* levels were largely unchanged. It would appear that the major overall determining factor in the rapid clearance of excess iron in thalassemia patients and the maintenance of normal iron stores is the selection and implementation of effective chelation dose protocols. The International Committee on Chelation (ICOC) combination protocol L1 (80-110 mg/kg/day)/DFO (40-60 mg/kg at least 3 days per week) and to a lesser extent, DFO monotherapy at about 50 mg/kg/day, 5 days/week, appears to achieve this goal.

International survey of T2* cardiovascular magnetic resonance in -thalassemia major

“…A major co-ordinated international effort is needed to continue to improve access to T2* CMR, although the provision of affordable and adequate transfusions and iron chelation therapy are primary issues. 5 Renzo Galanello, 6 Fabrice Danjou, 6 Gianluca Forni, 7 Antonis Kattamis, 8 Vassilis Ladis, 8 Marouso Drossou, 9 Demetra Vini, 9 Andreas Michos, 10 Vassilios Perifanis, 11 Tuncay Hazirolan, 12 Ana Almeida, 13 Yesim Aydinok, 14 Selen Bayraktaroglu, 14 Mirella Rangelova, 15 Denka Stoyanova, 16 Valeria Kaleva, 17 Georgi Tonev, 18 Amal El-Beshlawy, 19 Mohsen Elalfy, 20 Ibrahim Al-Nasser, 21 Wing-Yan Au, 22 Shau-Yin Ha, 22 Chi-Kong Li, 23 Winnie Chiu-Wing Chu, 23,24 Lee-Lee Chan, 25 Meng-Yao Lu, 26 Lia Wahidiyat, 27 Manuela Merelles-Pulcini, 28 Juliano de Lara Fernandes, 29 Fernando Kay, 30 P. Joy Ho, 31 Jane S. Hankins, 32 Maria Cappellini, 33 Shahina Daar, 34 Jameela Sathar, 35 Ali Taher, 36 George Kontoghiorges, 37 …”

“…20,21 Other countries have also reported improved management of cardiac iron using T2* CMR. [22][23][24][25] Whilst myocardial T2* has shown strong prognostic value in the UK cohort for prediction of cardiac complications, 26 the data are limited on the burden of cardiac iron loading or the application of CMR T2* in different parts of the world. We therefore performed an international survey of centers that use T2* to assess its wider clinical application and the degree of myocardial iron loading in a "real-life" setting.…”

Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases

“…The apparent increase in survival of TM patients is observed in Cyprus, and also many other countries using related chelation therapy and similar supportive therapy protocols [25][26][27][28][29] . The transition leading to the longer term survival outcome appears to be related to the improved compliance in the oral chelation therapy and more importantly to the ability of L1 to mobilise rapidly excess iron deposits from the heart, which has also been repeatedly confirmed in several thalassaemia centers using the T2* and T2 relaxation time MRI techniques [54,55,111,116] . The ability of L1 to reverse cardiac, liver, kidney and possibly other organ or tissue iron related damage in dif-ferent categories of patients and its antioxidant properties provide further evidence of its potent therapeutic effects [69,70] .…”

“…Within this context clinical studies have shown that the most effective treatment of transfusional iron overload is the use of L1/DF combination protocols and particularly the International Committee On Chelation (ICOC) protocol (L1 at 75-100 mg/kg per day and DF at 40-60 mg/kg at least 3 d per week). This protocol appear to reduce serum ferritin and to increase MRI T2* of the heart and liver progressively to physiological normal levels [110][111][112][113][114] . Furthermore L1 monotherapy (85-100 mg/kg per day) appears to be sufficiently effective for maintaining the body iron stores at normal physiological levels in most TM patients [112,114] .…”

Examination of echocardiographic parameters for the early diagnosis of cardiac dysfunction in beta thalassemia major patients

“…Several procedures have been used to detect the iron load in the heart. Echocardiography is a non-invasive, repeatable, and relatively inexpensive technique that is capable of the absolute diagnosis of heart diseases (5 (8). T2* magnetic resonance allows for the preclinical detection of myocardial iron load, the prospective categorization of the cardiac risks, and the observation of the response to changes in chelation therapy (9).…”