Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Efficacy of hematopoietic cell transplantation in beta thalassemia major

Emanuele Angelucci, MD
Section Editor
Robert S Negrin, MD
Deputy Editor
Jennifer S Tirnauer, MD


The first successful hematopoietic cell transplantations (HCT) in beta thalassemia major (BTM) were reported in 1982 [1,2]. Since that time, more than 3000 such transplants have been performed worldwide [3]. HCT has since become an accepted worldwide-applied curative option for those with BTM.

The efficacy of HCT in BTM will be reviewed here [4]. Other issues related to transplantation in this disorder, including the pre-transplant evaluation, conditioning regimens, recurrence of thalassemia, degree of replacement of the thalassemic stem cell with a normal stem cell, and long term follow-up are discussed separately. (See "Specific issues related to hematopoietic cell transplantation in beta thalassemia" and "Long-term management of the thalassemic patient after hematopoietic cell transplantation".)


This review deals with the treatment of subjects with homozygous beta thalassemia (beta thalassemia major, BTM). When the general term "thalassemia" is used, it will refer only to those with BTM.

The term "hematopoietic cell transplantation (HCT)" will be used throughout this review as a general term to cover transplantation of hematopoietic progenitor (stem) cells from any source (eg, bone marrow, peripheral blood, cord blood). Otherwise, the source of such cells will be specified. (See "Sources of hematopoietic stem cells".)


Rationale — The rationale for performing hematopoietic cell transplantation (HCT) in beta thalassemia major (BTM) is that it substitutes the high degree of ineffective erythropoiesis associated with BTM with an allogeneic stem cell capable of effective erythropoiesis, while avoiding transfusion requirements and their attendant complications. HCT in thalassemia is therefore a form of cellular replacement therapy and serves as a model of HCT for nonmalignant diseases.


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: May 2017. | This topic last updated: Nov 24, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Thomas ED, Buckner CD, Sanders JE, et al. Marrow transplantation for thalassaemia. Lancet 1982; 2:227.
  2. Lucarelli G, Polchi P, Izzi T, et al. Allogeneic marrow transplantation for thalassemia. Exp Hematol 1984; 12:676.
  3. Baronciani D, Elauroci N, Dini G, Peters C. Spreading and outcome of hemopietic stem cell transplantation in beta thalassemia major. Data from EBMT registry. Bone Marrow Transplant 2011; 46:S67.
  4. Angelucci E, Matthes-Martin S, Baronciani D, 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.
  5. Lucarelli G, Polchi P, Galimberti M, et al. Marrow transplantation for thalassaemia following busulphan and cyclophosphamide. Lancet 1985; 1:1355.
  6. Lucarelli G, Galimberti M, Polchi P, et al. Marrow transplantation in patients with advanced thalassemia. N Engl J Med 1987; 316:1050.
  7. Lucarelli G, Galimberti M, Polchi P, et al. Bone marrow transplantation in patients with thalassemia. N Engl J Med 1990; 322:417.
  8. Lucarelli G, Galimberti M, Polchi P, et al. Marrow transplantation in patients with thalassemia responsive to iron chelation therapy. N Engl J Med 1993; 329:840.
  9. Lucarelli G, Clift RA, Galimberti M, et al. Marrow transplantation for patients with thalassemia: results in class 3 patients. Blood 1996; 87:2082.
  10. Lucarelli G, Clift RA, Galimberti M, et al. Bone marrow transplantation in adult thalassemic patients. Blood 1999; 93:1164.
  11. Angelucci E, Baronciani D. Allogeneic stem cell transplantation for thalassemia major. Haematologica 2008; 93:1780.
  12. Di Bartolomeo P, Santarone S, Di Bartolomeo E, et al. Long-term results of survival in patients with thalassemia major treated with bone marrow transplantation. Am J Hematol 2008; 83:528.
  13. Gaziev D, Polchi P, Galimberti M, et al. Graft-versus-host disease after bone marrow transplantation for thalassemia: an analysis of incidence and risk factors. Transplantation 1997; 63:854.
  14. Angelucci E, Barosi G, Camaschella C, et al. Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders. Haematologica 2008; 93:741.
  15. Lucarelli G, Gaziev J. Advances in the allogeneic transplantation for thalassemia. Blood Rev 2008; 22:53.
  16. Chiesa R, Cappelli B, Crocchiolo R, et al. Unpredictability of intravenous busulfan pharmacokinetics in children undergoing hematopoietic stem cell transplantation for advanced beta thalassemia: limited toxicity with a dose-adjustment policy. Biol Blood Marrow Transplant 2010; 16:622.
  17. Bertaina A, Bernardo ME, Mastronuzzi A, et al. The role of reduced intensity preparative regimens in patients with thalassemia given hematopoietic transplantation. Ann N Y Acad Sci 2010; 1202:141.
  18. Mathews V, Savani BN. Conditioning regimens in allo-SCT for thalassemia major. Bone Marrow Transplant 2014; 49:607.
  19. Gaziev J, Sodani P, Polchi P, et al. Bone marrow transplantation in adults with thalassemia: Treatment and long-term follow-up. Ann N Y Acad Sci 2005; 1054:196.
  20. Gaziev J, Marziali M, Isgrò A, et al. Bone marrow transplantation for thalassemia from alternative related donors: improved outcomes with a new approach. Blood 2013; 122:2751.
  21. Li C, Wu X, Feng X, 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.
  22. Jawdat DM, Al Saleh S, Sutton P, et al. Chances of finding an HLA-matched sibling: The Saudi experience. Biol Blood Marrow Transplant 2009; 15:1342.
  23. Shamsi Ts, Hashmi K, Adil S, et al. The stem cell transplant program in Pakistan--the first decade. Bone Marrow Transplant 2008; 42 Suppl 1:S114.
  24. Elbjeirami WM, Abdel-Rahman F, Hussein AA. Probability of finding an HLA-matched donor in immediate and extended families: the Jordanian experience. Biol Blood Marrow Transplant 2013; 19:221.
  25. Klein T, Yaniv I, Stein J, et al. Extended family studies for the identification of allogeneic stem cell transplant donors in Jewish and Arabic patients in Israel. Pediatr Transplant 2005; 9:52.
  26. Ottinger H, Grosse-Wilde M, Schmitz A, Grosse-Wilde H. Immunogenetic marrow donor search for 1012 patients: a retrospective analysis of strategies, outcome and costs. Bone Marrow Transplant 1994; 14 Suppl 4:S34.
  27. Locatelli F, Rocha V, Reed W, et al. Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease. Blood 2003; 101:2137.
  28. Nabbara K, Locatelli F, Rocha V, et al. A multicentric comparative analysis of outcomes of HLA identical related cord blood and bone marrow transplantation in patients with beta-thalassemia or sickle cell disease. Biol Blood Marrow Transplant 2008; S1.
  29. Locatelli F, Kabbara N, Ruggeri A, et al. Outcome of patients with hemoglobinopathies given either cord blood or bone marrow transplantation from an HLA-identical sibling. Blood 2013; 122:1072.
  30. Fiorentino F, Biricik A, Karadayi H, et al. Development and clinical application of a strategy for preimplantation genetic diagnosis of single gene disorders combined with HLA matching. Mol Hum Reprod 2004; 10:445.
  31. Verlinsky Y, Rechitsky S, Sharapova T, et al. Preimplantation HLA testing. JAMA 2004; 291:2079.
  32. La Nasa G, Argiolu F, Giardini C, et al. Unrelated bone marrow transplantation for beta-thalassemia patients: The experience of the Italian Bone Marrow Transplant Group. Ann N Y Acad Sci 2005; 1054:186.
  33. Fleischhauer K, Locatelli F, Zecca M, et al. Graft rejection after unrelated donor hematopoietic stem cell transplantation for thalassemia is associated with nonpermissive HLA-DPB1 disparity in host-versus-graft direction. Blood 2006; 107:2984.
  34. La Nasa G, Littera R, Locatelli F, et al. Status of donor-recipient HLA class I ligands and not the KIR genotype is predictive for the outcome of unrelated hematopoietic stem cell transplantation in beta-thalassemia patients. Biol Blood Marrow Transplant 2007; 13:1358.
  35. Gaziev D, Galimberti M, Lucarelli G, et al. Bone marrow transplantation from alternative donors for thalassemia: HLA-phenotypically identical relative and HLA-nonidentical sibling or parent transplants. Bone Marrow Transplant 2000; 25:815.
  36. Sodani P, Isgrò A, Gaziev J, et al. Purified T-depleted, CD34+ peripheral blood and bone marrow cell transplantation from haploidentical mother to child with thalassemia. Blood 2010; 115:1296.
  37. Jaing TH, Chen SH, Tsai MH, et al. Transplantation of unrelated donor umbilical cord blood for nonmalignant diseases: a single institution's experience with 45 patients. Biol Blood Marrow Transplant 2010; 16:102.
  38. Jaing TH, Hung IJ, Yang CP, et al. Unrelated cord blood transplantation for thalassaemia: a single-institution experience of 35 patients. Bone Marrow Transplant 2012; 47:33.
  39. Ruggeri A, Eapen M, Scaravadou A, et al. Survey of outcomes of unrelated cord blood transplant in patients with haemoglobinopathies: a retrospective study on behalf of CIBMTR, NYCB and EUROCORD. Bone Marrow Transplant 2010; 45:378.
  40. Bernardo ME, Piras E, Vacca A, et al. Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan. Blood 2012; 120:473.
  41. Hsieh MM, Kang EM, Fitzhugh CD, et al. Allogeneic hematopoietic stem-cell transplantation for sickle cell disease. N Engl J Med 2009; 361:2309.
  42. Centis F, Tabellini L, Lucarelli G, et al. The importance of erythroid expansion in determining the extent of apoptosis in erythroid precursors in patients with beta-thalassemia major. Blood 2000; 96:3624.
  43. Andreani M, Manna M, Lucarelli G, et al. Persistence of mixed chimerism in patients transplanted for the treatment of thalassemia. Blood 1996; 87:3494.
  44. Andreani M, Nesci S, Lucarelli G, et al. Long-term survival of ex-thalassemic patients with persistent mixed chimerism after bone marrow transplantation. Bone Marrow Transplant 2000; 25:401.
  45. Alfred A, Vora AJ. What is the minimum level of donor chimerism necessary to sustain transfusion independence in thalassaemia? Bone Marrow Transplant 2011; 46:769.
  46. Borgna-Pignatti C, Rugolotto S, De Stefano P, et al. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 2004; 89:1187.
  47. Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008; 86:480.
  48. Modell B, Khan M, Darlison M, et al. Improved survival of thalassaemia major in the UK and relation to T2* cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2008; 10:42.
  49. Scalone L, Mantovani LG, Krol M, et al. Costs, quality of life, treatment satisfaction and compliance in patients with beta-thalassemia major undergoing iron chelation therapy: the ITHACA study. Curr Med Res Opin 2008; 24:1905.
  50. Orsi C, Bartolozzi B, Messori A, Bosi A. Event-free survival and cost-effectiveness in adult acute lymphoblastic leukaemia in first remission treated with allogeneic transplantation. Bone Marrow Transplant 2007; 40:643.
  51. Lucarelli G, Weatherall DJ. For debate: bone marrow transplantation for severe thalassaemia (1). The view from Pesaro (2). To be or not to be. Br J Haematol 1991; 78:300.
  52. Jagannath VA, Fedorowicz Z, Al Hajeri A, Sharma A. Hematopoietic stem cell transplantation for people with ß-thalassaemia major. Cochrane Database Syst Rev 2014; :CD008708.
  53. King A, Shenoy S. Evidence-based focused review of the status of hematopoietic stem cell transplantation as treatment of sickle cell disease and thalassemia. Blood 2014; 123:3089.
  54. Bozkurt G. Results from the north cyprus thalassemia prevention program. Hemoglobin 2007; 31:257.