Abstract
Allogeneic hemopoietic stem cell transplantation (HSCT) is the only method currently available to cure transfusion-dependent thalassemia major that has been widely used worldwide. To verify transplantation distribution, demography, activity, policies and outcomes inside the European Group for Blood and Marrow Transplantation (EBMT), we performed a retrospective non-interventional study, extracting data from the EBMT hemoglobinopathy prospective registry database. We included 1493 consecutive patients with thalassemia major transplanted between 1 January 2000 and 31 December 2010. In total, 1359 (91%) transplants were performed on patients <18 years old, 1061 were from a human leukocyte Ag-identical sibling donor. After a median observation time of 2 years, the 2-year overall survival (OS) and event-free survival (EFS; that is, thalassemia-free survival) were 88±1% and 81±1%, respectively. Transplantation from a human leukocyte Ag-identical sibling offered the best results, with OS and EFS of 91±1% and 83±1%, respectively. No significant differences in survival were reported between countries. The threshold age for optimal transplant outcomes was around 14 years, with an OS of 90–96% and an EFS of 83–93% when transplants were performed before this age. Allogeneic HSCT for thalassemia is a curative approach that is employed internationally and produces excellent results.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Thomas ED, Buckner CD, Sanders JE, Papayannopoulou T, Borgna-Pignatti C, De Stefano P et al. Marrow transplantation for thalassaemia. Lancet 1982; 2: 227–229.
Lucarelli G, Polchi P, Izzi T, Manna M, Agostinelli F, Delfini C et al. Allogeneic marrow transplantation for thalassemia. Exp Hematol 1984; 12: 676–681.
Angelucci E, Matthes-Martin S, Baronciani D, Bernadine F, Bonanomi S, Cappellini MD et al. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: Indications and management recommendations from an international expert panel. Haematologica 2014; 99: 811–820.
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J et al. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15: 825–828.
Marubini E, Valsecchi MG (eds). Analysing Survival Data from Clinical Trials and Observational Studies. Wiley: New York, 2004.
Lucarelli G, Galimberti M, Polchi P, Angelucci E, Baronciani D, Giardini C et al. Bone marrow transplantation in patients with thalassemia. N Engl J Med 1990; 322: 417–421.
Lucarelli G, Galimberti M, Polchi P, Angelucci E, Baronciani D, Giardini C et al. Marrow transplantation in patients with thalassemia responsive to iron chelation therapy. N Engl J Med 1993; 329: 840–844.
Lucarelli G, Galimberti M, Polchi P, Giardini C, Politi P, Baronciani D et al. Marrow transplantation in patients with advanced thalassemia. N Engl J Med 1987; 316: 1050–1055.
Modell B, Darlison M . Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008; 86: 480–487.
Sabloff M, Chandy M, Wang Z, Logan BR, Ghavamzadeh A, Li CK et al. HLA-matched sibling bone marrow transplantation for beta-thalassemia major. Blood 2011; 117: 1745–1750.
Mathews V, George B, Deotare U, Lakshmi KM, Viswabandya A, Daniel D et al. A new stratification strategy that identifies a subset of class III patients with an adverse prognosis among children with beta thalassemia major undergoing a matched related allogeneic stem cell transplantation. Biol Blood Marrow Transplant 2007; 13: 889–894.
Angelucci E . Hematopoietic stem cell transplantation in thalassemia. Hematology Am Soc Hematol Educ Program 2010; 2010: 456–462.
Lucarelli G, Clift RA, Galimberti M, Angelucci E, Giardini C, Baronciani D et al. Bone marrow transplantation in adult thalassemic patients. Blood 1999; 93: 1164–1167.
Michlitsch JG, Walters MC . Recent advances in bone marrow transplantation in hemoglobinopathies. Curr Mol Med 2008; 8: 675–689.
Li C, Wu X, Feng X, He Y, Liu H, Pei F et al. A novel conditioning regimen improves outcomes in β-thalassemia major patients using unrelated donor peripheral blood stem cell transplantation. Blood 2012; 120: 3875–3881.
Choudhary D, Sharma S, Gupta N, Kharya G, Pavecha P, Handoo A et al. Treosulfan-thiotepa-fludarabine-based conditioning regimen for allogeneic transplantation in patients with thalassemia major: a single-center experience from North India. Biol Blood Marrow Transplant 2013; 19: 492–495.
Agarwal MB . Advances in management of Thalassemia. Indian J Pediatr 2009; 76: 177–184.
Anurathapan U, Pakakasama S, Rujkijyanont P, Sirachainan N, Songdej D, Chuansumrit A et al. Pretransplant immunosuppression followed by reduced-toxicity conditioning and stem cell transplantation in high-risk thalassemia: a safe approach to disease control. Biol Blood Marrow Transplant 2013; 19: 1259–1262.
Mathews V, George B, Viswabandya A, Abraham A, Ahmed R, Ganapule A et al. Improved clinical outcomes of high risk beta thalassemia major patients undergoing a HLA matched related allogeneic stem cell transplant with a treosulfan based conditioning regimen and peripheral blood stem cell grafts. PLoS One 2013; 8: e61637.
Cavazzana-Calvo M, Payen E, Negre O, Wang G, Heir K, Fusil F et al. Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia. Nature 2010; 467: 318–322.
Acknowledgements
We thank Arnaud Dalissier (study coordinator for the EBMT Paediatrics Working Party, Paris) for coordination of the study, data collection and data managements, and Evgenia Glocova (Children Cancer Research Institute, Vienna) for additional statistical support in the analysis. We thank Enago (www.enago.com) for the English language review.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
This study was conducted on behalf of the EBMT Pediatric Disease Working Party. This study was presented as oral communication at the 2011 American Society of Hematology meeting in San Diego, CA, USA and at the plenary session of annual meeting of the Italian Association of Hematology Naples 2011.
Appendix
Appendix
Appendix Contributing centers
The number of patients registered in the study period (2000–2010) is shown in parentheses.
Frankfurt, J. W. Goethe Universität, Kinderheilkunde lll (3); Ankara, Gazi University, Besevle (1); Shiraz, Nemazee Hospital (16); Marseille, Hôpital Timone Enfants (4); Würzburg, Universitätsklinikum (1); Paris, Hôpital Neckar des enfants malades (3); Basel, Universitätsspital Basel (1); Leiden, University Hospital (40); Ulm, Kinderklinik Universitätsklinikum, Abt. Peds. II (4); London, Hammersmith Hospitals NHS Trust (1); Copenhagen, Rigshospitalet (10); Paris, Hôpital St. Louis (8); Leuven, University Hospital Gasthuisberg (1); Stockholm, Karolinska University Hospital, Huddinge (7); Brussels, Institut Jules Bordet, Childrens Hospital (3); London, The Royal Free Hospital (11); London, Royal Marsden Hospital (3); Rome, Università "La Sapienza", Hem Faculty 1 (1); Besancon, Hôpital Jean Minjoz and St Jacques (1); Brussels, Clinique Universitaire St Luc (4); Oslo, Rikshospitalet, Department of Medicine, The National Hospital (2); Nijmegen, University Hospital (4); Cordoba, Hospital Reina Sofia (2); Utrecht, University Hospital UMCU (1); Santander, Hospital Universitario M. de Valdecilla (1); London, Great Ormond Street Hospital (4); Pescara, Ospedale Civile (18); Nantes, Hotel Dieu, CHU Nantes (1); Leeds, St. James’s University Hospital and The General Infirmary (11); Jerusalem, Hadassah University Hospital (40); Essen, Universitätsklinikum (5); Barcelona, Santa Creu i Sant Pau (3); Geneva, Hôpital Cantonal Universitaire (1); London, The London Clinic (2); Uppsala, University Hospital, Medical Clinic (3); Grenoble, CHV Grenoble (1); Clermont Ferrand, CRCTCP, CHU Estaing (3); Genova, Istituto Giannina Gaslini (4); Newcastle upon Tyne, Royal Victoria Infirmary (1); Lille, Hôpital Claude Huriez (2); Monza, Ospedale San Gerardo (1); Lund, University Hospital (4); Rome, Ospedale S. Camillo (2); Goteborg, CHECT Sahlgrenska University Hospital (2); Hannover, Medizinische Hochschule (7); Lisbon, Instituto Portugues de Oncologia (4); Torino, University Hospital (14); Zurich, Universitäts Kinderklinik (10); Berlin, Charité, Campus Virchow Klinikum (1); Napels, National Cancer Institute (3); Haifa, Rambam Medical Center (24); Sofia, Pediatric Hospital for Oncohematology and BMT (7); Belgrade, Mother+Child Health Institute (1); Ankara, GATA BMT Center, Etlik (10); Rome, Policlinico Tor Vergata, Fond. IME (146); Bristol, Royal Hospital for Sick Children (1); Riyadh, King Faisal Specialist Hospital (64); Ankara, Ihsan Dogramaci Childrens Hospital (Hacettepe) (21); Istanbul, University of Istanbul (10); Madrid, Hospital Universitario Materno Infantil Gregorio Maranon (1); Barcelona, Hospital M. Infantil, Vall d'Hebron (5); Münster, Universitätklinikum Münster (1); München, Universitätsklinikum Grosshadern, Med Klin lll (1); Manchester, Royal Children's Hospital (17); Nice, Hôpital de l'Archet 1 (2); Trieste, Istituto per I'Infanzia (4); San Giovanni Rotondo, Hospital Casa Sollievo Sofferenza (1); Barcelona, Hospital General Vall d'Hebron (7); Vienna, St. Anna Kinderspital (6); Pesaro, Ospedale San Salvatore (67); Tübingen, Universitätsklinikum, Pädiatrie (2); London, St George’s Hospital (2); Pavia, Policlinico IRCCS St Matteo (113); Tel Hashomer, Chaim Sheba Medical Cebter (10); Amman, King Hussein Cancer Centre (44); Klinik fuer Knochenmarktransplantation und Haematologie/Onkologie, Idar-Obestein, Germany (15); San Sebastian, Hospital Nostra Senora de Aranzazu (1); Miskolc, Postgraduate Medical School (1); Firenze, Azienda Ospedaliero Universitaria Meyer, Department of Paediatric Haematology Oncology (11); Bremen, Klinikum Bremen-Mitte, Inn. Med l (1); Hamburg, Universitätsklinikum Eppendorf (4); Antalya, Akdeniz University Medical School (123); Ankara, University of Ankara (26); Izmir, Ege University Medical Faculty, Bornova (22); Athens, Evanghelismos Hospital (1); Brussels, University Hospital (1); Paris, Hôpital Robert Debré, Hem-Immuno (3); Teheran, Shariati Hospital (52); Düsseldorf, Universitätsklinikum (4); Valencia, Hospital Universitario La Fe (1); Lyon, Hôpital Edouard Herriot (3); Strasbourg, Hôpital Hautpierre (2); Vandoeuvre-les-Nancy, Hôpital d'Enfants (1); Randwick, Sydney Children’s Hospital, Centre for Children’s Cancer (2); Alger, Centre Pierre et Marie Curie (26); Glasgow, Royal Hospital for Sick Children (3); Sidney, The Children’s Hospital at Westmead (2); Palma de Mallorca, Hospital Universitario Son Espases (1); Salamanca, Complejo Hospital (3); Madrid, Hospital Niño Jesus (1); Madrid, Hospital La Paz (5); Brescia, Universitá degli Studi di Brescia (2); Buenos Aires CEHT (1); Gent, University Hospital (1); Athens, Aghia Sophia Childrens Hospital (21); Petach-Tikva, Childrens Medical center (6); Rome, Rome Transplant Network¨Tor Vergata¨ University of Rome Stem Cell Transplant Unit (12); Istanbul Tip Fakultesi Iç (1); Sevilla, Hospital Universitario Virgen del Rocio (1); Sheffield, Teaching Hospitals NHS Trust, Royal Hallamshire Hospital (4); Birmingham, The Birmingham Children's Hospital (15); Bologna, Policlinico S. Orsola, Clin. Pediatrica lll (7); Pisa, University of Pisa (4); Gdansk, Medical University (1); Lyon, Institut d'Hématologie et d'Oncologie Pédiatrique (9); Dresden, Universitätsklinikum Carl Gustav Carus (3); Freiburg, Universitatsklinikum, Kinderklinik (5); Cagliari, Binaghi BMT Centre (42); Cagliari, Univer Studi (70); Milan, Istituto Scientifico H.S. Raffaele (58); Catania, Pediatric Unit-Policlinico (1); London, St Mary's Hospital (58); Antalya, Medical Park Hospitals (2); Rouen, Hôpital Charles Nicolle (2); Toulouse, Hôpital Purpan (1); Strasbourg H Hautepierre (3); Bordeaux, CHU Hopitalier Pellegrin-Enfants (1).
Rights and permissions
About this article
Cite this article
Baronciani, D., Angelucci, E., Potschger, U. et al. Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000–2010. Bone Marrow Transplant 51, 536–541 (2016). https://doi.org/10.1038/bmt.2015.293
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/bmt.2015.293
This article is cited by
-
Harmonizing definitions for hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism in allogeneic hematopoietic cell transplantation: a report on behalf of the EBMT, ASTCT, CIBMTR, and APBMT
Bone Marrow Transplantation (2024)
-
Magnetic resonance imaging assessment of the changes of cardiac and hepatic iron load in thalassemia patients before and after hematopoietic stem cell transplantation
Scientific Reports (2023)
-
Measles, mumps, and rubella revaccination in children after completion of chemotherapy and hematopoietic stem cell transplantation: a single-center prospective efficacy and safety analysis
World Journal of Pediatrics (2023)
-
Cell-Based Gene Therapy for β-Thalassemia
Indian Pediatrics (2023)
-
Is Old (Fludrabine/Busulfan/Cyclophosphamide/rAntiThymocyteGlobulin) Conditioning Still Gold for Allogeneic Transplants in Transfusion Dependent Beta-Thalassemia of All Risk Categories in 21st Century?
Indian Journal of Hematology and Blood Transfusion (2023)