13th International Conference on thalassaemia & haemoglobinopathies - Abstracts by Thalassaemia International Federation (TIF)

THALASSAEMIA INTERNATIONAL FEDERATION

13th International Conference on Thalassaemia & Haemoglobinopathies

Abstract Book by Thalassaemia International Federation (TIF)

Abu Dhabi Conference, 20-23 October 2013

Thalassaemia International Federation

CONTENTS:

Long term efficacy of interferon-a2b/peg-interferon-a2b monotherapy in patients with β-thalassemia and chronic hepatitis c infection. the significance of il-28b polymorphisms Alexandra Kourakli Phosphor 32 particles Radioembolization of the Spleen in thalassaemic patients: A case report Afshan Shirkavand Treatment of hepatitis C during major sickle cell syndromes Amel Dejnouni Malignancies in patients with β - Thalassemia Michael Hadjigavriel, Maria Sitarou, Annita Kolnagou, Soteroulla Christou Evaluation of thyroid ultrasound as a screening tool in patients with thalassemia Giangos Lavranos Malignancies in patients with β - Thalassemia Michael Hadjigavriel, Maria Sitarou, Annita Kolnagou, Soteroulla Christou The use of silymarin in treatment of thalassaemia Mahmoud Hadipour Dehshal Therapeutic Patient Education (TPE) for thalassemia major patients Marie Christine Medard Thromobotic events in Thalassemia population Michael Hadjigavriel Atrial Fibrillation in Thalassemia Michael Hadjigavriel Thalassaemia Modular Stratification System for personalized therapy of betathalassemia (THALAMOSS): from OMICS to personalized treatment of thalassemia Monica Fortini Vitamin D levels correlate with iron load and glycemic intolerance in thalassemia Soteroulla Christou

Abu Dhabi Conference, 20-23 October 2013

5 6 7

8 9 10 11 12 13

Thalassaemia International Federation

Alexandra Kourakli University of Patras Hospital, Patras Greece Long term efficacy of interferon-a2b/peg-interferon-a2b monotherapy in patients with β-thalassemia and chronic hepatitis c infection. the significance of il-28b polymorphisms BACKGROUND AND PURPOSE: HCV infection and iron overload are the main causes of liver disease in ¦Â-TM. Since there is concern about ribavirin treatment, interferon-α2b (IFN-α2b) remains the standard first-line treatment. Recent data suggest that some polymorphisms in the interleukin-28B (IL-28B) gene are associated with sustained virological response (SVR). To assess the long-term efficacy of IFN-α2b monotherapy in HCV-infected thalassemic patients and the predictive factors for SVR. Patients & Methods: 48 ¦Â-TM HCV-infected patients [M/F: 19/29, median age 22 years (range 1245), 23/48 splenectomised] were treated with IFN-α2b (n=34) or PegIFN-α2b (n=14). Median ALT was 107 IU/ml (33-331) and median ferritin 1926.5 ng/ml (373-10820)]. Liver histology was: Ishak stage ¡Ý4: 13/39 (27.1%), and grade: 6 (3-10), siderosis grade 3-4: 23/43 (47.9%). Median follow-up was 165.5 months (8-237). HCV genotype was -1 (47.2%), -2 (5.6%), 3 (25%) and -4 (22%). IL-28B genotype was determined with a RT-PCR, using genomic DNA, extracted from frozen serum samples, in conjunction with minor groove binder probes: CC: 27%, CT: 62.2%, TT: 10.8%. RESULTS: Totally, 15/48 (31.3%) patients achieved SVR following the first treatment course; 13 (27.1%) received multiple courses (2-5), and 3 of them achieved SVR. Therefore, SVR at the end of follow-up was achieved by 18 patients (38.3%). Splenectomy (p=0.008) and fibrosis grade>4 (p=0.037) were negative predictive factors for SVR (first course), whereas splenectomy (p=0.024) and age >18 (p=0.02) were negative factors overall. In HCV-genotype 1, 100% of the patients with CC IL-28B genotype achieved SVR versus 18.2% of those with CT or TT (p=0.07). CONCLUSION: Interferon treatment for HCV-infected β-TM patients is as efficient as for non-thalassemics. Predictive factors for SVR are splenectomy, age and fibrosis. Although the number of patients is relatively low we found that all HCV-genotype1 patients, carrying CC IL-28B achieved SVR, and this finding deserves further investigation.

Abu Dhabi Conference, 20-23 October 2013

Thalassaemia International Federation

Afshan Shirkavand Pardis Noor Medical Imaging Centre, Iran Phosphor 32 particles Radioembolization of the Spleen in thalassaemic patients: A case report INTRODUCTION: phosphor-32 particles (32PRE) are used for transarterial Radioembolization of spleen. To the best of our knowledge, it has never been reported as a therapeutic approach instead of splenectomy in thalassaemic patients. PATIENTS AND METHODS: A 30-year-old man suffering from beta thalassaemia major with splenomegaly (SM) was referred for applying a less-invasive approach instead of sple e to y due to patie tâ&#x20AC;&#x2122;s e uest fo o su gi al t eat e t. He p og essed i to a aggressive clinical disease with a major enlargement of his spleen responsible for severe anemia with Hgb level of 6.6 gm/dl and platelet levels of 269000 (x 10-6/Liter) requiring frequent transfusions every 10-14 days. Before Radioembolization, his spleen size was determined by means of Sonography about 19.5 cm. In order to reduce the spleen size, 10 milicurie of 32P particles was selectively administered via the splenic artery, which corresponds to a roughly dose of?? Gy. This procedure was safe and led to shrinkage of spleen size into 15 cm while Hgb increased to 8 gm/dl and platelet to 369000 (x 106/Liter). DISCUSSION: Radioembolization is a well-known safe procedure for hepatic tumor treatment. Embolization procedure has been previously reported years ago with a successful outcome for congestive hypersplenism. Irradiation could injure adjacent organs. In our patient, 32PRE was well tolerated with reduction of spleen size. The complete normalization of the CBC suggests a major role of the irradiation in size reduction of spleen. The response duration was 3 months. CONCLUSION: This case report suggests that 32PRE is a safe and effective procedure that deserves further investigation in thalassaemic splenomegaly. Indeed, this procedure was better tolerated than invasive operation, with preserving part of spleen and impressive results of transfusion reduction in this patient.

Abu Dhabi Conference, 20-23 October 2013

Thalassaemia International Federation

Amel Dejnouni Annaba Hospital, Hematology Centre, Annaba, Algeria Treatment of hepatitis C during major sickle cell syndromes BACKGROUND: The prevalence of hepatitis C in major sickle cell syndromes is important. The frequency varies between studies and populations from 2 to 30%, but with an average of 14% compared to the general population (03%). The treatment of hepatitis C in the hemoglobinopathies is a challenge for practitioners, given the risk of hemolytic Ribavérine. The aim of our study is to evaluate the safety, antiviral efficacy of anti-HCV in patients followed for a major sickle cell syndrome. MATERIAL AND METHOD: This is a prospective study concerned 17 patients with sickle cell disease with hepatitis C and candidates for HCV treatment. Regular monitoring is carried out weekly in collaboration: hematologist or gastroenterologist infectious disease specialist. RESULTS: The average age of our cohort was 27 years with extremes [20-56 years], the study concerned 03 men and 14 women. 13 patients were homozygous and 04 had S / B thalassemia, the average viral load of 3.49 log [2.5 - 7.83], HCV genotype 1b was in 58.82% cases. A PBF performed in 14 patients, without incidents and with the histological study highlights a METAVIR score of A1F1 (35.71%) and A1F2 (28.57%). A comprehensive review pre-treatment, in search of a comorbidity is made. Treatment was associated with: - Pegylated interferon + ¨ Ribavérine: n: 16 - Interferon alone: n: 01 Some complications were collected on treatment: - 03 cases of vaso-occlusive crises with bone pain requiring hospitalization. - Fall in hemoglobin base in both cases and requiring a blood transfusion - No cases of leukopenia or thrombocytopenia. CONCLUSION: From this study it is noted that the hematological tolerance of anti-HCV treatment is excellent with acceptable transfusion requirements, which may consider the use of ribavérine immediately in optimal doses in this population, since the combination therapy provides better viral response.

Abu Dhabi Conference, 20-23 October 2013

Thalassaemia International Federation

Michael Hadjigavriel, Maria Sitarou, Annita Kolnagou, Soteroulla Christou Cyprus Thalassaemia Centres Malignancies in patients with Î˛ - Thalassemia BACKGROUND AND PURPOSE: Different survival studies identified cancer as a cause of death in patients with Ă˘-thalassaemia. The aim of this study was to assess the frequency of cancer, the pattern of malignancies and possible predisposing factors in patients with thalassaemia major( TM) and intermedia (TI). METHODS AND MATERIALS: A total of 633 patients (542 TM / 91 TI) were enrolled. They represent thalassaemia population attending four centers in Cyprus. The follow up period was 1993 - 2013. Diagnosis of malignancy was based on clinical, laboratory and histological data. We recorded demographic data, serum ferritin, chelation treatment, hepatitis status, type and incidence of malignancy. RESULTS: A total of 18 patients (2.84%) were diagnosed with cancer of which 7(38.88%) presented hepatocellular carcinoma (HCC), 2 patients breast cancer and 2 patients leukemia. Seven others were found to have kidney adenocarcinoma, melanoma, osteosarcoma, Hodgkins, Non Hodgkins, adenocarcinoma of the colon and papillary thyroid. 11 patients had TM and 7 TI. Mean age at presentation was 40 years (24-65). Most cases 10/18 (55.55%) observed during the 2nd and 3rd decade. Chronic HBV and cirrhosis were diagnosed in 1/7 (14.27%) patients with HCC. Antibodies against HCV were detected in 1/7 (14.27%) patients. Four out of seven patients (57.14%) with HCC had TI (mean age, 62 years) and developed HCC without a history of hepatitis. Mean s. ferritin at the time of diagnosis was 1725 ng/ml (259-9500). Most patients were treated with DFO or combination of DFO and DFP. 3/18 patients were received hydroxyurea at the time of the event. CONCLUSION: A broad spectrum of malignancies has been determined in our population. HCC was the most frequently identified especially in older TI patients. Predisposing factors other than infections should be considered. Iron overload and oxidative stress might be suggested to explain the occurrence of malignancy in those patients.

Abu Dhabi Conference, 20-23 October 2013

Thalassaemia International Federation

Giangos Lavranos Scientific Associate, Thalassaemia International Federation, Nicosia, Cyprus Evaluation of thyroid ultrasound as a screening tool in patients with thalassemia BACKGROUND AND PURPOSE: Among the many complications of thalassemia, the most prominent ones include cardiomyopathy, cirrhosis and multiple endocrine dysfunction. The use of thyroid ultrasound has not so far been proposed as a screening tool for the early detection of thyroid disease. The aim of this study was to evaluate the thyroid ultrasound as a screening test in this population. METHODS AND MATERIALS: All patients with beta thalassemia major or intermediate presenting in the Nicosia Thalassemia Centre during the first 6 months of 2012 were submitted to thyroid ultrasound by a certified radiologist. In addition, ferritin and TSH levels were measured. In total, 209 patients were included, of which 90 males and 119 females. 27 patients suffered from thalassemia intermedia and 182 from thalassemia major. Mean age was 42.69 years (SD: 9.57). RESULTS: 16 patients presented with abnormal ultrasound findings (7.65%). Most of these included thyroid nodules of less than 1 cm. These were more common among women (12/119, 10.08%) than men (4/90, 4.44%) and among thalassemia intermedia patients (3/27, 11.1%) than major (13/182, 7.1%). However, using the X-square test (Xsquare=2.3 and 0.52 respectively), these differences were not statistically significant. In terms of yield, 4 patients required treatment due to abnormal ultrasound and TSH values (1.91%), all of which were female (3.36% of females, indicative but not significant Xsquare for sex, 3.08) and 3/4 were thalassemia major cases. In one case the patient was diagnosed with thyroid follicular carcinoma. CONCLUSION: Thyroid ultrasound is a non-invasive, simple and low cost diagnostic assay for the early diagnosis of thyroid disease. In patients with beta thalassemia, abnormal findings appear to be more frequent than the general population. The study supports the use of thyroid ultrasound as a screening assay, although larger, multicentre trials are needed.

Abu Dhabi Conference, 20-23 October 2013

Thalassaemia International Federation

Abu Dhabi Conference, 20-23 October 2013

Thalassaemia International Federation

Mahmoud Hadipour Dehshal Iranian Blood Transfusion Organisation, Teheran, Iran The use of silymarin in treatment of thalassaemia BACKGROUND AND PURPOSE: B-Thalassaemia is the name given to a group of inherited blood disorders that affect the body's ability to create red blood cells. One of its complications is Iron overload which can stir a set of oxidative stress and accordingly damage to the heart, liver and endocrine system, which includes glands that produce hormones that regulate processes throughout the body. In the current study, we aim to evaluate Silybum marianum L to find out that its usefulness in B-thalassemia major patie tsâ&#x20AC;&#x2122; t eat e t. METHODS AND MATERIALS: considering potential benefits of flavonoids in the therapy of oxidative stress, the effects of silymarin on the intracellular glutathione (GSH) levels and proliferation of PHA-activated peripheral blood mononuclear cells (PBMC), it can normalize immune dysfunction in B-thalassemia major. Some studies on silymarin indicated that the extract from milk thistle had antiviral effects against hepatitis C virus cell culture; hence, it can be used for those thalassaemics exposed to HCV. Recently, silymarin combined with deferoxamine have been used in reducing iron overload. Therefore, fresh studies about silymarin suggest its potential effectiveness in reducing body iron burden. RESULTS: According to our evaluation, silymarin has therapeutic effects on thalassaemia treatment and can be taken together with other thalassaemia medicines. In the end of this e ie , e suggest that o e studies should e o du ted o sily a i â&#x20AC;&#x2122;s effectiveness on the process of thalassaemia treatment.

Abu Dhabi Conference, 20-23 October 2013

Thalassaemia International Federation

Marie Christine Medard Centre de reference Thalassemie, France Therapeutic Patient Education (TPE) for thalassemia major patients BACKGROUND AND PURPOSE: The aim of TPE programs is to allow patients suffering from chronic diseases to acquire abilities (in psycho-social domains or self-care management) to better manage their life with their disease. METHODS: an TPE program concerning 40 beta-thalassemia major patients aged 15 years or more and treated in our center (Marseille, France) was implemented in October 2012. RESULTS: After informed consent, an educational diagnosis was conducted using semistructured interview in order to identify with the patient what are the main incentives and obstacles (psychological, social, behavioral and environmental) modulating his involvement in his own health care and treatment observance. Next the patient built his personal program by choosing several individual or group sessions among the 8 following: 1) succeeding the transition from children to adults 2) filling my medical folder in 3) where am I from my iron overload? 4) I am splenectomized, what else ? 5) hard to live with a chronic disease ! 6) take my treatment every day, yes I can ! 7) I take care of my body 8) my personal way of life. Sessions were organized in small groups with a multidisciplinary team (nurse, dietetician, physiotherapist, psychologist and social worker, expert-patient, physician). After clarification of the objective of the session, all participants discuss their needs and problems concerning the topic (observance, sports,..) and how they are able to cope with. Most often information leaflets are also provided. Annual evaluation of the program including quantitative and qualitative data (evolution in ferritin levels, in observance questionnaires, patient satisfaction regarding the global program...) is required by health authorities. CONCLUSION: in June 2013, 20 patients were included. TPE program has already modified the relationships between patients who now constitute a real group able to help the more vulnarable of them.

Abu Dhabi Conference, 20-23 October 2013

Thalassaemia International Federation

Michael Hadjigavriel Thalassaemia Unit, Limassol Hospital, Limassol, Cyprus Thromobotic events in Thalassemia population BACKGROUND AND PURPOSE: Thrombotic complications resulting from a hypercoagulable state has been described in thalassaemia particularly in splenectomized patients with thalassaemia intermedia. The aim of this study was to calculate the incidence of thromboembolic events (TEEs), and review the characteristics and risk factors in patients with thalassaemia major (TM) and thalassaemia intermedia (TI). METHODS AND MATERIALS: One hundred sixty two patients were assessed for a mean duration of follow up 27 years. Mean age: 38 years. Eighty seven patients (54%) were splenectomized. Eighty three patients considered having thalassaemia major and 79 patients considered having thalassaemia intermedia. Almost all patients were regularly or occasionally transfused and received iron chelation treatment. Demographic, clinical and laboratory data, transfusion state and history of events were recorded. RESULTS: A total of 18 patients (7 males, 11 females) who experienced 23 TEEs were identified. TEEs consisted of: DVT: 8 cases (34.78%), pulmonary embolism: 4 cases (17.39%), CVA: 4 cases (17.39%), portal vein thrombosis: 3 cases (13.04%), superficial thrombophlebitis: 3 cases (13.04%), priapism: 1 case (4.34%). The mean age of patients at the time of the thrombotic event was 33.8Âą11.7 years (range 22-72) and the mean time after splenectomy was 17.4Âą16.3 years. Three cases with PVT occurred within 2 weeks after splenectomy. The overall incidence was 11.11% (8.43% in TM and 13.92% in TI). However, there was no statistically significant difference between the two groups (p=0.4). All these events occurred in the splenectomized patients (p<0.0001). CONCLUSION: TEEs are complications of the relatively older patients and occurred several years after splenectomy. The exclusive occurrence of TEEs in splenectomized patients may suggest a strong association between these two conditions. In contrast to other studies we did not find any significant difference in the incidence of thrombosis between TM and TI.

Abu Dhabi Conference, 20-23 October 2013

Thalassaemia International Federation

Michael Hadjigavriel Thalassaemia Unit Limassol Hospital, Limassol Cyprus Atrial Fibrillation in Thalassemia BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is a significant predictor of morbidity in thalassaemia. Despite improved prognosis with better chelation therapy a high incidence of AF still exists particularly in the aging population even in the absence of significant iron overload. The aim of this study was to determine the incidence, risk profile and outcomes of patients with beta-thlassaemia diagnosed with AF. METHODS AND MATERIALS: We studied 162 patients (mean age: 38 years) with thalassaemia from a single center during a period of 13 years. Clinical, laboratory and echocardiography data were recorded. The incidence of AF events was calculated. All patients were transfused regularly and received iron chelation treatment. RESULTS: A total of 13 patients presented with AF. The overall incidence of AF was 8% and in patients above 40 years was 19%. Mean age at the first event was 50 years. 62% of patients in AF (8/13) had diabetes. Seven out of 13 patients (54%) had thalassaemia intermedia. Most of the patients 8/13 (62%) had mild left atrial dilatation (mean: 42 mm) at the time of the first event. None had symptoms of cardiac failure. Mean ejection fraction was 64% (range, 46-71%). Serum ferritin at the time of the first event was relatively low (median: 960 ng/ml) in the majority of patients. The median heart T2* was 34 msec, however 3 patients had cardiac T2* less than 20 msec. AF was associated with adverse outcomes like stroke (1 patient), transient ischemic attack (2 patients), major bleeding due to anticoagulation (1 patient) and repeat hospitalization (all patients). The majority 9/13 (69%) developed chronic AF. CONCLUSION: AF is an important complication with severe outcomes in thalassaemia. Older age, diabetes, and left atrial dilatation may be some risk factors for AF, however more data from prospective multicenter studies are needed to confirm these findings.

Abu Dhabi Conference, 20-23 October 2013

Thalassaemia International Federation

Monica Fortini Day Hospital for thalassaemia and haemoglobinopathies, S. Anna Hospital, Ferrara, Italy THALAssaemia MOdular Stratification System for personalized therapy of beta-thalassemia (THALAMOSS): from OMICS to personalized treatment of thalassemia AIMS. THALAMOSS (www.thalamoss.eu, started 11/2012) aims to develop a universal sets of markers and techniques for stratification of 창-thalassaemia patients into treatment subgroups for (a) onset and frequency of blood transfusions, (b) choice of iron chelation, (c) induction of fetal hemoglobin, (d) prospective efficacy of gene-therapy. WORKPACKAGES. WP1. Recruitment, patient characterization and development of culture technologies for erythroid precursor cells; WP2. Omics analyses; WP3. Novel therapeutic approaches; WP4. Data management and analysis; WP5. Dissemination and exploitation; WP6. Regulatory and ethical issues; WP7. Program management. IMPACT. Provision of novel biomarkers for distinct treatment subgroups in 창thalassaemia (500-1000 samples from participating medical centres), identified by combined genomics, proteomics, transcriptomics and tissue culture assays. Development of new or improved products for the cell isolation, characterisation and treatment of 창thalassaemia patients. Establishment of routine techniques for detection of these markers and stratification of patients into treatment groups. EXPECTED PRODUCTS. Translation of these activities into the product portfolio and R&D methodology of participating SMEs will be a major boost for them as well as for the field. THALAMOSS tools and technologies will (a) facilitate identification of novel diagnostic tests, drugs and treatments specific to patient subgroups and (b) guide conventional and novel therapeutic approaches for 창-thalassaemia, including personalised medical treatments.

Abu Dhabi Conference, 20-23 October 2013

Thalassaemia International Federation

Soteroulla Christou Cyprus Thalassaemia Centre, Nicosia Cyprus Vitamin D levels correlate with iron load and glycemic intolerance in thalassemia BACKGROUND AND PURPOSE: Vitamin D is a steroid hormone involved in a number of metabolic and developmental processes, including bone turnover and tissue regeneration. In thalassemia, low vitamin D values are common and they are associated with increased bone disease progression and fracture incidence. However, less is known about its role in further endocrine disruption in this population. This study aimed to examine the correlation between vitamin D levels, iron load and glucose intolerance in thalassemia METHODS AND MATERIALS: All patients with beta thalassemia major without overt diabetes presenting in the Nicosia Thalassemia Centre during May 2013 were submitted to consecutive testing for serum ferritin, fasting glucose and insulin, parathormone and vitamin D levels. In total, 75 patients were included, of which 33 (44%) male and 42 (56%) female. Mean age was 38.59 years (SD: 7.8). RESULTS: Mean vitamin D value was 31.11 (SD:10.73), with 32 individuals (42.67%) below the threshold of 30. Using the Pearson r correlation coefficient, vitamin D serum values were weakly negatively correlated at a statistically significant (p<0.05) degree to serum ferritin (r=-0.2187), parathormone (r=-0.270), fasting insulin (r=-0.239) and HOMA index (r=-0.216). Contrary to this finding, no significant correlation to fasting glucose or HBA1C% values could be detected. CONCLUSION: Vitamin D insufficiency is a common disorder in beta thalassemia major, affecting about half of young adult patients. Apart from bone health (where it partially counteracts parathyroid deficiency), vitamin D also serves as a marker of iron overload / chelation adherence and correlates to early indicators of insulin resistance, such as fasting insulin and the HOMA index. HBA1c% does not seem to be an accurate predictive test in the pre-diabetic setting in this special population.

Abu Dhabi Conference, 20-23 October 2013