GUIDELINES FOR THE MANAGEMENT OF TRANSFUSION DEPENDENT THALASSAEMIA (TDT) 3RD EDITION Editors Cappellini MD Cohen A Porter J Taher A Viprakasit V PUBLISHERS THALASSAEMIA INTERNATIONAL FEDERATION TIF PUBLICATION NO. 20 ISBN 978-9963-717-06-4 All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any from or by any means, electronic, mechanical, photocopying, microfilming, recording or otherwise, without written permission from TIF. Printed in Nicosia, Cyprus. ©2014 Team up Creations Ltd 14 Othonos str., 1016 Nicosia PUBLISHERS Thalassaemia International Federation P.O. Box 28807, Nicosia 2083, Cyprus Tel. +357 22 319 129 Fax. +357 22 314 552 Email: [email protected] Website: www.thalassaemia.org.cy GUIDELINES FOR THE MANAGEMENT OF TRANSFUSION DEPENDENT THALASSAEMIA (TDT) EDITORS Cappellini MD Cohen A Porter J Taher A Viprakasit V Acknowledgement Thalassaemia International Federation greatly appreciates the assistance of Evida Medical Ltd for the final editing and proofreading of the text . Cure sometimes, treat often, comfort always. Hippocrates (460-357 B.C.) The good physician treats the disease; the great physician treats the patient who has the disease. Sir William Osler (1849-1919) TABLE OF CONTENTS FOREWORD 10 Panos Englezos and Androulla Eleftheriou INTRODUCTION 12 THE NEED FOR GUIDELINES AND THEIR IMPLEMENTATION Maria Domenica Cappellini CHAPTER 1: 14 GENETIC BASIS, PATHOPHYSIOLOGY AND DIAGNOSIS Vip Viprakasit and Raffaella Origa CHAPTER 2 28 BLOOD TRANSFUSION Sara Trompeter and Alan Cohen CHAPTER 3 42 IRON OVERLOAD AND CHELATION John Porter and Vip Viprakasit CHAPTER 4 98 CARDIAC COMPLICATIONS Malcolm Walker and John Wood CHAPTER 5 114 LIVER DISEASE Pierre Brissot CHAPTER 6 126 THE SPLEEN Ali Taher and Paul I Tyan CHAPTER 7 134 INFECTIONS Yesim Aydinok CHAPTER 8 146 ENDOCRINE DISEASE Vincenzo De Sanctis, Nicos Skordis and Ashraf Soliman 4 CHAPTER 9 158 FERTILITY AND PREGNANCY Nicos Skordis CHAPTER 10: 170 OSTEOPOROSIS Ersi Voskaridou and Evangelos Terpos CHAPTER 11 178 DENTAL CARE Navdeep Kumar and Faiez Hattab CHAPTER 12 186 HAEMOPOIETIC STEM CELL TRANSPLANTATION Emanuele Angelucci, Alok Srivastava and Sara Usai CHAPTER 13 192 ALTERNATE AND NOVEL APPROACHES Maria Domenica Cappellini and Vijay G Sankaran CHAPTER 14 198 GENE THERAPY Michel Sadelain, Farid Boulad, Isabelle Riviere and Aurelio Maggio CHAPTER 15 210 PSYCHOLOGICAL SUPPORT Robert Yamashita, Lauren Mednick and Dru Haines CHAPTER 16 224 LIFESTYLE AND QUALITY OF LIFE Michael Angastiniotis CHAPTER 17 236 ORGANISATION AND PROGRAMMING OF THALASSAEMIA CARE Michael Angastiniotis and Androulla Eleftheriou 5 EDITORS AND AFFILIATIONS Cappellini Maria Domenica, Professor of Haematology, Department of Medicine and Medical Specialties, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Foundation Maggiore Policlinico Hospital, Milan, Italy Cohen Alan, Professor of Paediatrics, University of Pennsylvania, School of Medicine, USA Porter John, Professor of Haematology, Head of the Thalassaemia and Sickle Cell Unit, Haematology, Department, University College London, UK Taher Ali, Professor of Medicine, Hematology & Oncology, Director of Department of Internal Medicine, American University of Beirut – Medical Centre, Lebanon Viprakasit Vip, Associate Professor of Haematology, Division of Paediatric Haematology/ Oncology at Siriraj Hospital, Mahidol University, Bangkok and Programme Coordinator for Thalassaemia Research at Siriraj-Thalassaemia Centre, Bangkok, Thailand AUTHORS, REVIEWERS AND AFFILIATIONS Angastiniotis Michael, Paediatrician, Medical Advisor at the Thalassaemia International Federation (TIF), Cyprus Angellucci Emanuele, Professor of Haematology, Unità operativa di Ematologia e Centro Trapianti di Cellule Staminali Emopoietiche. Ospedale oncologico di riferimento regionale “Armando Businco”, Cagliari, Italy Aydinok Yesim, Professor of Paediatric Haematology, Department of Pediatric Hematology, Ege University Hospital, Izmir, Turkey Brissot Pierre, Professor of Medicine, Liver Disease Specialist, Service des Maladies du Foie, Hôpital Pontchaillou, Rennes University Hospital, Rennes, France Cappellini Maria Domenica, Professor of Haematology, Department of Medicine and Medical Specialties, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Foundation Maggiore Policlinico Hospital, Milan, Italy Cohen Alan, Professor of Paediatrics, University of Pennsylvania, School of Medicine, USA De Sanctis Vincenzo, Paediatric Endocrinologist, Quisisana Hospital, Ferrara, Italy Eleftheriou Androulla, Executive Director, Thalassaemia International Federation (TIF), Cyprus 6 Fucharoen Suthat, Professor of Hematology, Thalassaemia Research Center, Institute of Molecular Bioscience, Mahidol University, Nakornprathom, Thailand Haines Dru RN, Specialist Nurse, Children’s Hospital and Research Center, Oakland, CA USA Hattab Faiez N., Professor and Senior Consultant in Restorative Paediatric Dentistry, Amman, Jordan. Kumar Navdeep, Consultant/Honorary Lecturer in Special Care Dentistry, Eastman Dental Hospital, London, UK Maggio Aurelio, Professor of Haematology, Director of Regional Center for Thalassaemia, Haematology II with Thalassaemia, 'V. Cervello' Hospital, Palermo, Italy Mednick L. Lauren, Psychologist, Boston Children’s Hospital, Harvard Medical School, Boston MA USA Origa Rafealla, Paediatrician , Hospitale Regionale, Microcitemie ASL, Clinica Pediatrica 2, University of Cagliari, Italy Porter John, Professor of Haematology, Head of the Thalassaemia and Sickle Cell Unit, Haematology, Department, University College London, UK Sadelain Michel, Director, Center for Cell Engineering & Gener Transfer and Centre Expression Laboratory, Memorial Sloan Kettering Cancer Centre, New York, USA. Sankaran Vijay G., Haematologist Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA Skordis Nicos, Paediatric Endocrinologist, Division of Paediatric Endocrinology, Department of Paediatrics, Archbishop Makarios III Hospital, Nicosia, Cyprus Soliman Ashraf T., Professor of Paediatric Endocrinology, Department of Paediatrics, Division of Endocrine, Hammad General Hospital, Doha, Qatar Srivastava Alok, Professor of Haematology, Department of Hematology, Centre for Stem Cell Research, Christian Medical College, Vellore, India Taher Ali, Professor of Medicine, Hematology & Oncology, Director of Department of Internal Medicine, American University of Beirut – Medical Centre, Lebanon Terpos Evangelos, Hematologist Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece. Trompeter Sara, Consultant Haematologist & Paediatric Haematologist, Joint Red Cell Unit, University College Hospital, London, UK 7 Tyan Paul I., Department of Physiology, Faculty of Medicine, American University of Beirut, Lebanon. Usai Sara, Haematologist, Unità operativa di Ematologia e Centro Trapianti di Cellule Staminali Emopoietiche. Ospedale oncologico di riferimento regionale “Armando Businco”, Cagliari, Italy Voskaridou Ersi, Director, Thalassaemia Centre, Laikon General Hospital, Athens, Greece Walker Malcolm, Consultant Cardiologist, Hatter Institute, University College London Hospital, London, UK Wood John, Paediatric Radiologist, Department of Paediatrics, Children’s Hospital, Los Angeles, University of Southern California, USA Yamashita Robert C., Sociologist, California State University San Marcos, CA USA INDEPENDENT REVIEWERS AND AFFILIATIONS Kalakoutis Gabriel, Obstetrician, Aretaieio Private Hospital, Nicosia, Cyprus. Ex-director, Obstetrics and Gynaecology, Makarios III Hospital Nicosia Kattamis Antonis, Associate Professor of Paediatric Hematology-Oncology, Thalassemia Unit, Head First Department of Paediatrics, University of Athens, 'Agia Sofia' Children's Hospital, Athens, Greece Yardumian Anne, Consultant Haematologist, Associate Medical Director, Patient Safety, North Middlesex University Hospital, London, UK 8 9 FOREWORD It is now established that the hereditary haemoghlobin disorders, previously lethal from childhood, can now be treated as chronic conditions, in which the patient may aspire to a long and productive life. This requires optimum lifelong care, which in turn requires physician experience and patient cooperation. Both depend on adherence to internationally accepted and evidence based guidelines. It is an ethical requirement to provide accurate and unbiased information and the quality of information is an essential element in offering good quality patient care. Thalassaemia International Federation (TIF) through a panel of experts has published guidelines both for transfusion dependent thalassaemia as well as non-transfusion dependent thalassaemia. This is one of the main objectives of the creation of the Thalassaemia International Federation, which was established in 1987 with the objective to promote care which will result in improved survival and a good quality of life. Through these guidelines quality, evidence based information is offered for the clinicians to help them in their effort to provide the best possible care, in a chronic disease that becomes more complex as the patient grows in years. Well treated thalassaemia will lead the patient beyond childhood, to an age where there is multiple organ involvement. The consequences, mainly of iron overload, cannot be totally prevented even by present day iron chelation treatment.