TIF International Conference 2003 - Programme

THALASSEMIA AND HEMOGLOBINOPATHIES October 15th 05:00 pm OPENING CEREMONY -TIF Organizing Committee Award to Bernadette Modell - Delivering of Panos Englezos and George Englezos Awards -Presentation of Award in honour of Professor Fessas -Presentation of the Russo-De Gregorio So.S.T.E. Award -Audio-conference with I. Bianco for the presentation of the prize for the best poster presented at the 2003 TIF congress, in memory of Prof.

Ezio Silvestroni, sponsored by Biorad The Era of Oral Chelation , Chaim Hershko COCKTAIL October 16th - Room A -Plenary Sessions SESSION 1 Molecular Genetics of Globin Genes : Any clues to therapies ?

Chairman : G. Stamatoyannopoulos Sub-session A Globin Gene Regulation Co-chairman : P. Ioannou 8:20 am 8:55 am 9:25 am 9: 45 am

10:15 am

Developmental Control of human Globin Genes G. Stamatoyannopoulos Control of hemoglobin switching. What is our current understanding ?

J. D. Engel Modelling Hemoglobin Switching N. P. Anagnou Highlights on the alfa globin genes regulation D. Higgs Break Sub-session B What is the current status of research on fetal hemoglobin inducers ?

Co-chairmen: S. Ottolenghi

10:30 am

Butyrate and other short chain fatty acids as therapeutics for

thalassemia and sickle cell disease S. S. Perrine 10:50 am Treatment of sickle cell anemia with decitabine: changes in clinical correlates, J. De Simone 11:10 am Treatment of beta thalassemia patients with fetal hemoglobin inducers, E. Vichinsky 11:30-12:00am Panel Discussion Chairman: M. Steinberg Panel Members: G. Stamatoyannopoulos, S. Ottolenghi, P. Ioannou ,S. S. Perrine, J. De Simone, E. Vichinsky , G. Evans, M. Steinberg, J. Restivo from Cooley’s Anemia Foundation and A. Ceci from Fondazione Italiana “L. Giambrone” per la Guarigione dalla Talassemia on : a) the current status in the field of hemoglobin inducers ; b) steps required to bring an inducer from the lab to the clinic; c) the role of biotechnology and pharmaceutical industry; d) the need of involvement of lay organizations; e) the need to organize international experimental treatment protocols.

Sub-session C Gene therapy for thalassemia: Will it become a reality?

Co-chairmen: L. Naldini and T. Papayannopoulou 12:00 pm

Development of molecular therapies for the beta chain hemoglobinopathies M. Sadelain 12:20 pm Lentivirus vectors and gene therapy of hemoglobinopathies P. Leboulch 12:40 pm Use of Chromatin Insulators to Prevent Silencing of Globin Gene Vectors D. W. Emery 1:00 pm Role of a sea urchin insulator sequence in erythroid cells S. Acuto 1:10 pm The need for bone marrow ablation: the example of ADA A. Aiuti 1:30-2:15pm Panel Discussion Chairman: S. Rivella

Panel Members: M. Sadelain, P. Leboulch, R. Storb, L. Naldini, T. Papayannopoulou, S. Rivella, D.W. Emery, S. Acuto, A. Aiuti, P. D. Noguchi, G. Evans, J. Restivo from Cooley’s Anemia Foundation and A. Ceci from Fondazione Italiana “L. Giambrone” per la Guarigione dalla Talassemia on : a) will there be problems with regulatory approval of lentiviral vectors ? b) will the retroviral vectors be effective in vivo ? c) what are the expectations of applications of globin gene therapy without ablation ? d) will ablation be accepted by patients and physicians ? e) who will produce the vectors in practice ? f) how will gene therapy be delivered in practice ? g) what will be the cost ? h) Is it possible to think about an international project on gene therapy of hemoglobinopathies ? i) what are the predictions of the panel about time table ?

2:15 pm

LUNCH

SESSION 2 Bone Marrow Transplantation Session: what is old and what is new ?

Chairmen : A. Bacigalupo and E. Angelucci 3:15 pm

Allogenic hematopoietic cell transplantation after nonmyeloablative conditioning R. Storb 3:40 pm State of the art and new protocols for thalassemia BMT G. Lucarelli 4:00 pm Alternative hematopoietic stem cells donors for bone marrow transplantation in thalassemia F. Locatelli 4:20 pm Long-term follow-up after bone marrow transplantation in thalassemia, E. Angelucci 4:40 –5:15pm Panel Discussion Chairman : B. Wonke Panel Members: A.Bacigalupo, E.Angelucci, R.Storb, G.Lucarelli, F.Locatelli, S.Slavin, M.D. Cappellini, B. Wonke on : a) which is the role of BMT today considering that patients in low-risk class have been already transplanted and remaining subjects are in the majority of cases in high risk class ? b) which is the role of the alternative bone marrow transplantation

5:15 pm

procedures ?

Break

SESSION 3 In Utero Transplantation Session. Which is the state of art ?

Chairmen: A. Salerno and S. Slavin 5:30 pm

Ontogenesis of the human immunological system , F. Dieli 5:50 pm In utero hematopoietic stem cell transplantation : an overview E. Zanjani 6:15 pm Experience with in utero transplantation in hemoglobinopathies MC Renda 6:25 pm-7:15 Panel Discussion Chairman : S. Slavin Panel Members: A. Salerno, S. Slavin, F. Dieli, E. Zanjani , A. Maggio, M.C. Renda, G. Damiani, R. Storb on : a ) will IUT become a reality ? b) failures of IUT : bone marrow space or immunological problems? c) will it be possible to induce tolerance by IUT ?

October 17th - Room A (Plenary) SESSION 4 Epidemiology and Prevention Session: what is changing ?

Chairmen: M. Angastiniotis and A. Loutradi 8:20 am 8:50 am 9:10 am 9:35 am

Worldwide epidemiology and heterogeneity of haemoglobinopathies in the Third Millenium D. Weatherall The UK National Haemoglobinopathy Screening Programme: one of the models for delivering genetic services to the community M. Petrou Prenatal diagnosis of hemoglobinopathies: an overview A. Cao Pre-implantation Genetic Diagnosis of thalassemia A. Kuliev

SESSION 5 Genotype –phenotype correlation Chairmen: R. Galanello and P. Giordano

10:00 am 10:20 am 10:40 am 11:00 am

Genetic counselling, diagnosis and clinical management of thalassemia intermedia: a guidelines proposal D. Loukopoulos Hemoglobin E disorders: pathophysiology and clinical findings, S. Fucharoen Strategy to detect hemoglobin variants with beta-thalassemia phenotype, H. Wajcman Cellular mechanisms of inefficacious erythropoiesis, S.L. Schrier

11:20-11:50am Panel Discussion Chairman : D. Weatherall Panel Members: M. Angastiniotis, A. Loutradi, D. Loukopoulos, S. Fucharoen, H. Wajcman, D. Weatherall, S. Schrier, A. Cao, R. Galanello, P. Giordano, M. Petrou, E. Vichinsky, A. Kuliev on : a) may prenatal diagnosis of hemoglobinopathies today depend on the genotype ? b) is it possible today to predict phenotype by the genotype and in which cases ? c) is it possible to organize an international consortium to collect a significative number of data on genotype-phenotype correlation ? d) who could be the sponsors of this consortium ?

11:50 am

Break

SESSION 6 Liver Disease in Thalassemia Chairman: G. Fiorelli and L. Pagliaro 12:05 pm 12:20 pm

Natural History of Chronic Liver Disease, A. CraxĂŹ Iron and Liver,

A. Pietrangelo 12:35 pm Treatment of C Hepatitis in Thalassemia, V. Di Marco 12:50 pm Perspectives of Liver Transplantation in Thalassemia, J. Fung 1:05 – 1:35pm Panel Discussion Chairman : A.R. Cohen Panel Members: G. Fiorelli, L. Pagliaro, A. Craxi, A. Pietrangelo, V. Di Marco, J. Fung , B. Wonke , A. Cohen , E. Angelucci , J. Lerut on : a) how to improve the prevention of liver disease in thalassemia ; b) role today of liver transplantation in hemoglobinopathies.

1:35 pm

LUNCH

SESSION 7 Alterations in coagulation state Chairmen: G. Mariani and R. Musso 3:15 pm

New highlights on prevention and treatment of congenital and acquired thrombophilia disorders P.M. Mannucci 3:40 pm Activation of the coagulation system by pathological RBC from different etiologies E. Rachmilewitz 3:55 pm Causes of hypercoagulable state in thalassemia M.D. Cappellini 4:10 pm Causes of hypercoagulable state in sickle cell syndromes S.H. Embury 4:25-4:55pm Panel Discussion Chairman : P.M. Mannucci Panel Members:G. Mariani, R. Musso, P.M. Mannucci, E. Rachmilewitz, M.D.Cappellini, S.H. Embury and the participation of S. Fucharoen , E. Vichinsky , D. Loukopoulos on :

4:55 pm

SESSION 8

a) when, which and how long anti-coagulation treatment ? b) post-splenectomy thrombocytosis : an absolute indication for treatment ? c) which risk of long-term anti-coaugulation treatment ?

Break

Endocrine complications Chairmen: G. Tolis and B. Wonke 5:10 pm

The role of TIF in medical education of growth disorders and endocrine complications in thalassemia, A. Eleftheriou 5:25pm International multicentre study on short stature and endocrine complications in thalassemia, V. De Sanctis 5:45 pm Transdermal estradiol replacement therapy in hypogonadic thalassemic females : 14 years of experience A. Allegra 6:05 pm Evolution of glucose homeostasis disturbances in thalassemia patients: a prospective study of 20 years C. Kattamis 6:25 pm Update on fertility in thalassemia major N. Skordis 6:45 pm Psychosocial aspects of endocrine complications in thalassemia,O. Platis 7:05-7:35 pm Panel Discussion Chairman: V. De Sanctis Panel Members: G. Tolis, B. Wonke , A. Eleftheriou, V. De Sanctis, A. Allegra, C. Kattamis, N. Skordis, O. Platis D. Loukopoulos and M. Angastiniotis on : a) proposal guidelines for pregnancy in thalassemia and sickle cell anemia; b) osteoporosis , which treatment ? c) fertility in males : a guidelines proposal for diagnosis and treatment.

October 18th - ROOM A (Plenary) SESSION 9 Heart Problems Chairmen: M. Walker and D. Kremastinos 8:25 am

New insights in the heart failure : an overview, G. Derchi 8:45 am Pathogenesis of the heart involvement in thalassemia, L. Mancuso 9:05 am Cardiac involvement in thalassemia intermedia, A. Aessopos 9:25 am Proposal of guidelines for Heart Transplantation in Thalassemia, R. Ruggiero 9:45-10:15 am Panel Discussion

Chairman: D. Th. Kremastinos Panel Members: M. Walker , D. Kremastinos,G. Derchi, L. Mancuso, A. Aessopos, R. Ruggiero and with the contribution of E. Vichinsky and J. Porter on : a) which are the most sensitive and specific parameters to prevent heart involvement in thalassemia ? b) there is significant medical evidence about hyperchelation advantage during heart failure in thalassemia patients ? c) the changing in the prognosis can justify an increased use of heart and lung transplantation in these patients ?

10:15 am

Break

SESSION 10 Non invasive determination of iron in thalassemia Chairman: A. Cohen and E. Vichinsky 10:30 am

General principles of the measurement of iron in the body F. T. Jensen 10:50 am SQUID biomagnetometry : past experience and new applications for the future, R. Fischer 11:10 am Nuclear Magnetic Resonance to evaluate liver and heart iron in thalassemia P.D. Jensen 11:30 am T2* (star) in the evaluation of liver and myocardial iron overload M. Westwood 11:50-12:30pm Panel Discussion Chairman: E. Vichinsky Panel Members: A. Cohen, F. T. Jensen, R. Fisher, P.D. Jensen, M. Westwood B. Wonke, E. Vichinsky, A. Maggio, A. Piga on : a) T2* with respect to the other T2 methods; b) guidelines proposal to standardize NMR for liver and heart iron detection; c) will it be possible to have in the future a SQUID procedure for the heart ? d) what is changing on the management of thalassemia with the use of non invasive determination procedures; e) status of validation of MRI methods.

SESSION 11 Blood Transfusions Chairman: P. Bonomo 12:30 pm

New insights about laboratory investigations of transfusions treatment C. Politis 12:45 pm An estimate of the current risk of transmitting blood-borne infections through blood transfusions, D. Prati 1:00-1:30 pm Panel Discussion Chairman: C. Politis Panel Members: P. Bonomo, C. Politis , D. Prati ,G. Fiorelli, A. Craxi, V. Di Marco and A. Elefteriou on : a) how is it possible to improve blood donations ? b) how is it possible to reduce the residual risk of transfusion-transmitted infection ?

1:30 pm LUNCH

SESSION 12 Sickle Cell and ß-thalassemia/Sickle Cell Disease Chairmen: S. Charache and G. Schiliro’ 3:00 pm

The treatment of pain in Sickle Cell Anemia, S.K. Ballas 3:20 pm The role of blood transfusion and iron chelation in Sickle Cell Disease, J. Porter 3:40 pm Long-term treatment with hydroxyurea in sickle cell anemia M. Steinberg 4:00 pm Modulation of Gardos channel activity and of other membrane systems in sickle erythrocytes C. Brugnara 4:20pm Sickle-Cell Anaemia in Saudi Arabia, M. A.F. El-Hazmi 4:35pm Hydroxyurea in Sicilian beta-thalassemia/Sickle Cell Disease patients: results of long-term treatment study P. Rigano 4:45-5:15pm Panel Discussion Chairman: S. Charache Panel Members: S. Charache , G. Schilirò, S.K. Ballas, M. Steinberg, C. Brugnara, M. A.F. El-Hazmi, P. Rigano, J. Porter,J. De Simone , E. Vichinsky, D. Loukopoulos , S.H. Embury on :

a) safety of hydroxyurea in paediatrics and in pregnancy ; b) long-term treatment risks of HU like carcinogenesis and fertility; c) may the other drugs like modulators of Gardos channel activity and of other membrane systems become a reality in the prevention of sickle cell crises ? d) complications and transfusions; e) role of NO treatment; f) endothelial mechanism of sickling and treatment.

5:15 pm

Break

SESSION 13 Iron chelation treatment Chairmen: C. Gluud and P. Giardina 5:30 pm

Iron chelation treatment : an overview A. Piga 5:50pm Multicenter clinical trials as the main tool to evaluate effectiveness and safety of chelators A. Maggio 6:10 pm Effects of combination treatment with L1 and DF to clear iron from the heart, B. Wonke 6:30 pm Future perspectives from new iron chelators R. Galanello 6:50-7:35 pm Panel Discussion Chairman: C. Gluud Panel Members: C. Gluud, P. Giardina, A. Piga, A. Maggio, S. Charache, B. Wonke, R. Galanello and the participation of A. Cohen , C. Kattamis, on: a) prognosis and evaluation of treatments : guidelines for the RCT’s ( by C. Gluud ); b) which is the best hyperchelation treatment and when it is indicated? c) which is the most right strategy to study effectiveness and safety of new oral chelators ?

October 19th - ROOM A (Plenary) SESSION 14 PSYCHOSOCIAL Problems

Chairmen: G. Masera and O. Platis 9:00 am 9:20 am 9:40 am 10:00 am

Planning the future across fears and hopes P. Massaglia Iron chelation and quality of the life J.B. Porter Thalassemia - problem and perspectives G. Costantinou Sickle cell disease, psycoemotional implications and art therapy intervention C. Favara Scacco

10:15-11:00am Panel Discussion Chairman: P. Englezos Panel Members: P. Englezos, G. Masera, O. Platis, P. Massaglia, J. B. Porter, G. Costantinou, C. Favara Scacco on: a) become parents for thalassemia patients b) what support for thalassemic adolescent? c) which new goals for thalassemia associations?

11:00 am

Break

SESSION 15 DEVELOPING COUNTRIES : HOW TO IMPROVE THEIR PREVENTION AND TREATMENT FACILITIES ?

Chairman: S. Fucharoen 11:15 am

TIF’s efforts in promoting prevention and treatment in the developing world A. Eleftheriou

11:30 am

World Summit for Children revisited: did we keep the promises ?

A. Paganini The Iran experience on thalassemia services A. Samavat

11:45am 12:00 pm

The Maldives experience on thalassemia prevention programme, N. Firdous 12:15 pm An experience from Congo on Sickle Cell Disease management, L. Tshilolo 12:30 pm Prevention programme in Palestine, Thalassemia Patients Friends Society (TPFS)

12:45pm Il ruolo dell’associazionismo nei processi di riscatto dei territori fortemente segnati dal crimine organizzato G. Cipriani 1:00 pm

Panel Discussion Chairman: A. Paganini Predetermined communication: Developing awareness of Thalassemia in Brazil, Fernando Devia, Regional Manager Bio-Rad Latin America 1:10pm Panel Members: V. Boulyjenkov for WHO, A. Paganini for UNICEF, A. Elefteriou, A. Samavat, N. Firdous, L. Tshilolo, S. Tuli, F Hashemi, Neelam Dhingra, S. Fucharoen, Mohamed El-Nageh and Lt General Ahmed Fahim Khan on : a ) is it possible to allocate specific resources to improve prevention and treatment facilities in developing countries and who can do this? b) which are the priorities ?

1:40 pm

LUNCH

15:30 pm

DO LAY ORGANIZATIONS HAVE A ROLE IN THE DEVELOPMENT OF NEW THERAPIES FOR THALASSEMIA ?

Chairman: ?

Panel Members: P. Englezos for TIF, J. Restivo for Cooley’s Anemia Foundation, A. Iacono for Fondazione “Leonardo Giambrone”, R. Borsellino for Associazione per la Ricerca “Piera Cutino” Onlus on: a) discussing the possibility of a common policy of “fund raising” by the organization of an international event; b) organizing a political pressure on governments; c) establishing a common theme, development of an international strategic plan to cure thalassemia by 2010; d) establishing an international coordinator committee to pursue the plan; e) devising a mechanism to influence policy makers in EU and US governments

17:30 pm

-Delivering of Award in honour of Professor Fessas -Delivering of Russo-De Gregorio So.S.T.E. Award -Audio-conference with I. Bianco for the delivering of the Prof. Ezio Silvestroni prize, sponsored by Biorad

CONCLUSIONS

October 17th – Room Rinaldo – Parallel session Chaiman : ?

11:45 am

12:45 am

Patent protection as an Incentive tool for Research and Development in the Field of Genetic and Metabolic Diseases ?

Conclusion

October 18th – Room Angelica – Parallel session Nursing in Thalassemia Chaimen : R. Malizia and C. Magnano 9:00 am 9:20 am 9:40 am 10:00 am

Communication between nurses and patients in thalassemia P. Massaglia Therapeutic steps: global nursing in thalassemia A. Piga Prevention of Hemoglobinopathies: nursing function?

M. Capra Conclusion

TIF CONFERENCE October 14th Arrivals October 15th Paladini Room 10:00 am 2:30 pm

Board Meeting Associations Workshop Co-ordinators: M.Michael, Panos Englezos, M. Haraoui Collaboration of TIF with and promotion of National Thalassaemia Associations, covering: - patients services - publications: preparation, translation & distribution

- government collaboration / pressure - organisation of events - fund raising October 16th GENERAL MEETING & ASSOCIATIONS SEMINAR 8:30 am

General Meeting Agenda according to Constitution Patients meet patients Discussion Co-ordinated by available patient or physician Parallel session

9:30 am 10:00 am 1:00 pm

2:00 pm 2:15 pm 2:30 pm 2:50 pm 3:00 pm 3:20 pm 3:30 pm 3:50 pm 4:10 pm

Coffee break Constitutional General Meeting LUNCH Blood Safety Chairpersons: A.Eleftheriou, R. Ficarra Donation Policies, C. Politis BT Services, C. Politis An estimate of the current risk of transmitting blood-borne infections through transfusion, Daniele Prati Discussion Treatment of thalassaemias Transfusion therapy / TA reactions, A. Cohen Discussion Iron Chelation, A. Piga Progress of New Iron Chelators, P. Giardina Coffee break BMT and Management of complications Chairpersons: M.D. Cappellini, R. Elbard

4:40 pm 5:00 pm

BMT and other approaches, J. Porter Heart problems in thalassaemia major, M. Walker

5:20 pm

Use of MRI in assessing iron overload, D. Pennel

5:40 pm

Endocrine complications in thalassaemia major, V. De Sanctis Liver Disease in thalassaemia, V. Di Marco Panel discussion, N. Skordis, E. Angelucci, R. Galanello, G. Constantinou, O. Platis, M. Fanari

6:00 pm 6:20 pm

October 17th Psychosocial aspects Chairperson: P. Massaglia - M. Angastiniotis 8:30 am 10:00 am 10:30 am

Round Table on Psychosocial aspects E.Georganda, O.Platis, P. Andreou, G. Constantinou Coffee break Global Collaboration I with WHO WHO Regional Offices ISBT & ICBS BS Unit WHO Chairpersons: A. Eleftheriou, Panos Englezos Parallel session

1:00 pm 2:30 pm 6:30 pm

Patients meet the experts Discussion Co-ordinated by available Patient and/or physician LUNCH Board Meeting II Summary of DAY 1 (16 October 2002) Molecular Aspects For all patients Summary of DAY 2 (17 October 2002) Molecular Aspects FOR ALL PATIENTS SATURDAY - 18 OCTOBER 2003 & SUNDAY - 19 OCTOBER 2003 Joint conference Sessions of the Scientific conference that are of common interest

Clinical aspects there will be translation into Greek , Italian and possibly Arabic (possibility under investigation). Parents and patients will have the opportunity to attend the scientific sessions if they wish to do so.

On Thursday afternoon, however, the same topics will be presented by the experts in a simpler language. As a consequence there is no need to have rapporteurs presenting the last day

WORKSHOPS Satellite SYMPOSIUM BIORAD

INCLUDERE IL PROGRAMMA DEFINITIVO

October 17th CittĂ del Mare Hotel 3:00 p.m.- 6:00 p.m. - Morgante Room ON THE SAME WAY FOR THE SAME GOAL Organization models and prevention strategies in different countries Scientific Committee Marcello Capra - Italy Aurelio Maggio - Italy Aphrodite Loutradi - Greece Piero Giordano - The Netherlands Suthat Fuchareon - Thailand Claudia Bonini - Brazil Panos Englezos - Cyprus Bio-Rad Laboratories has decided to award a prize for the best poster presented at the 2003 TIF congress, in memory of Prof. Ezio Silvestroni, a pioneer in the study of thalassaemias.

Satellite Symposium TOSOH BIOSCIENCE

INCLUDERE IL PROGRAMMA DEFINITIVO

October 18th Florio Park Hotel 2.30 pm - 7.30 pm - Conference Hall LABORATORY DIAGNOSIS OF HAEMOGLOBINOPATHY : RELIABILITY AND UNRELIABILITY Scientific Committee R. Galanello G. Ivaldi L. Leone A. Maggio A. Mosca F. Rigolin M.A. Romeo R. Testa Under the patronages of S.I.Me.L. , S.I.Bio.C. , A.I.Pa.C.

Note: a) Cambiare relazione John Old con Leonor Osorio; b) Cambiare orario per Galanello: dalle ore 18.00 alle ore 17.00 e spostare di conseguenza gli altri relatori.

AGGIUNGERE MINISATELLITE APOTEX-CHIESI-DEMO METTERE DATA, ORARIO, LUOGO E PROGRAMMA DEFINITIVO Satellite Symposium NOVARTIS Città del Mare Hotel October 18th 2.30 – 5.30 p.m. – Paladini room PHARMACOLOGICAL, CLINICAL AND REGULATORY ASPECTS IN THE DEVELOPMENT OF A NEW ORAL CHELATOR METTERE PROGRAMMA DEFINITIVO.

SE NON E’ PERVENUTO IL PROGRAMMA DEFINITIVO, LASCIARE COMUNICAZIONE DI DATA, LUOGO, ORARIO E TITOLO DEL MINISATELLITE.