Hemoglobinopathies (Sickle Cell Disease and Thalassemia)

  • Barbara Cappelli
  • Eliane GluckmanEmail author
  • Khaled Ghanem
  • Miguel R. Abboud


Sickle cell disease (SCD) is the most common inherited hemoglobinopathy worldwide.


  1. 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;25:401–4.CrossRefGoogle Scholar
  2. Angelucci E, Matthes-Martin S, Baronciani D, et al. EBMT Inborn Error and EBMT Paediatric Working Parties. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel. Haematologica. 2014;99:811–20.CrossRefGoogle Scholar
  3. Angelucci E, Pilo F, Coates TD. Transplantation in thalassemia: Revisiting the Pesaro risk factors 25 years later. Am J Hematol. 2017;92:411–3.CrossRefGoogle Scholar
  4. Arnold SD, Bhatia M, Horan J, Krishnamurti L. Haematopoietic stem cell transplantation for sickle cell disease - current practice and new approaches. Br J Haematol. 2016;174:515–25.CrossRefGoogle Scholar
  5. 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. 2016;51:536–41.CrossRefGoogle Scholar
  6. 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;120:473–6.CrossRefGoogle Scholar
  7. Bernaudin F, Socie G, Kuentz M, et al. SFGM-TC. Long-term results of related myeloablative stemcell transplantation to cure sickle cell disease. Blood. 2007;110:2749–56.CrossRefGoogle Scholar
  8. Bernaudin F, Verlhac S, Arnaud C, et al. Long-term treatment follow-up of children with sickle cell disease monitored with abnormal transcranial Doppler velocities. Blood. 2016;127:1814–22.CrossRefGoogle Scholar
  9. Bertaina A, Pitisci A, Sinibaldi M, Algeri M. T Cell-Depleted and T Cell-Replete HLA-Haploidentical Stem Cell Transplantation for Non-malignant Disorders. Curr Hematol Malig Rep. 2017;12:68–78.CrossRefGoogle Scholar
  10. Bhatia M, Jin Z, Baker C, et al. Reduced toxicity, myeloablative conditioning with BU, fludarabine, alemtuzumab and SCT from sibling donors in children with sickle cell disease. Bone Marrow Transplant. 2014;49:913–20.CrossRefGoogle Scholar
  11. Canver MC, Orkin SH. Customizing the genome as therapy for the beta-hemoglobinopathies. Blood. 2016;127:2536–45.CrossRefGoogle Scholar
  12. Cappelli B, Chiesa R, Evangelio C, et al. Absence of VOD in paediatric thalassaemic HSCT recipients using defibrotide prophylaxis and intravenous Busulphan. Br J Haematol. 2009;147:554–60.CrossRefGoogle Scholar
  13. Dallas MH, Triplett B, Shook DR, et al. Long-term outcome and evaluation of organ function in pediatric patients undergoing haploidentical and matched related hematopoietic cell transplantation for sickle cell disease. Biol Blood Marrow Transplant. 2013;19:820–30.CrossRefGoogle Scholar
  14. Dhedin N, de la Fuente J, Bernaudin F, et al. Haploidentical Bone Marrow Transplant with Post-Transplant Cytoxan Plus Thiotepa Improves Donor Engraftment in Patients with Sickle Cell Anemia: Results of an International Multicenter Learning Collaborative Trial. Blood. 2016;128:1233. (ASH Abstract).Google Scholar
  15. Foell J, Pfirstinger B, Rehe K, et al. Haploidentical stem cell transplantation with CD3(+)-/CD19(+)- depleted peripheral stem cells for patients with advanced stage sickle cell disease and no alternative donor: results of a pilot study. Bone Marrow Transplant. 2017;52:938–40.CrossRefGoogle Scholar
  16. 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;25:815–21.CrossRefGoogle Scholar
  17. Gaziev J, Nguyen L, Puozzo C, et al. Novel pharmacokinetic behavior of intravenous busulfan in children with thalassemia undergoing hematopoietic stem cell transplantation: a prospective evaluation of pharmacokinetic and pharmacodynamic profile with therapeutic drug monitoring. Blood. 2010;115:4597–604.CrossRefGoogle Scholar
  18. Gluckman E, Cappelli B, Bernaudin F, et al. Sickle cell disease: an international survey of results of HLA-identical sibling hematopoietic stem cell transplantation. Blood. 2017;129:1548–56.CrossRefGoogle Scholar
  19. Hamidieh AA, Moeininia F, Tayebi S, et al. Efficacy of hepatic T2* MRI values and serum ferritin concentration in predicting thalassemia major classification for hematopoietic stem cell transplantation. Pediatr Transplant. 2015;19:301–6.CrossRefGoogle Scholar
  20. Hamidieh AA, Shazad B, Ostovaneh MR, et al. Noninvasive measurement of liver fibrosis using transient elastography in pediatric patients with major thalassemia who are candidates for hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20:1912–7.CrossRefGoogle Scholar
  21. Johnson FL, Look AT, Gockerman J, et al. Bone-marrow transplantation in a patient with sickle-cell anemia. N Engl J Med. 1984;311:780–3.CrossRefGoogle Scholar
  22. Justus D, Perez-Albuerne E, Dioguardi J, et al. Allogeneic donor availability for hematopoietic stem cell transplantation in children with sickle cell disease. Pediatr Blood Cancer. 2015;62:1285–7.CrossRefGoogle Scholar
  23. Kim DW, Chung YJ, Kim TG, et al. Cotransplantation of third-party mesenchymal stromal cells can alleviate single-donor predominance and increase engraftment from double cord transplantation. Blood. 2004;103:1941–8.CrossRefGoogle Scholar
  24. Kwon M, Bautista G, Balsalobre P, et al. Haplo-cord transplantation using CD34+ cells from a third-party donor to speed engraftment in high-risk patients with hematologic disorders. Biol Blood Marrow Transplant. 2014;20:2015–22.CrossRefGoogle Scholar
  25. Law J, Cowan MJ, Dvorak CC, et al. Busulfan, fludarabine, and alemtuzumab as a reduced toxicity regimen for children with malignant and nonmalignant diseases improves engraftment and graft-versus-host disease without delaying immune reconstitution. Biol Blood Marrow Transplant. 2012;18:1656–63.CrossRefGoogle Scholar
  26. Li C, Wu X, Feng X, et al. A novel conditioning regimen improves outcomes in beta-thalassemia major patients using unrelated donor peripheral blood stem cell transplantation. Blood. 2012;120:3875–81.CrossRefGoogle Scholar
  27. Lucarelli G, Galimberti M, Giardini C, et al. Bone marrow transplantation in thalassemia. The experience of Pesaro. Ann N Y Acad Sci. 1998;850:270–5.CrossRefGoogle Scholar
  28. Lucarelli G, Galimberti M, Polchi P, et al. Bone marrow transplantation in patients with thalassemia. N Engl J Med. 1990;322:417–21.CrossRefGoogle Scholar
  29. Mathews V, George B, Deotare U, 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;13:889–94.CrossRefGoogle Scholar
  30. Mohty M. A bit of antithymocyte globulin can take you a long way! Bone Marrow Transplant. 2012;47:617–8.CrossRefGoogle Scholar
  31. National Heart, Lung, and Blood Institute. Evidence-based management of sickle cell disease. Expert Panel Report. Bethesda: National Heart, Lung, and Blood Institute; 2014.
  32. Piel FB, Hay SI, Gupta S, et al. Global burden of sickle cell anaemia in children under five, 2010-2050: modelling based on demographics, excess mortality, and interventions. PLoS Med. 2013;10:e1001484.CrossRefGoogle Scholar
  33. Ribeil JA, Hacein-Bey-Abina S, Payen E, et al. Gene Therapy in a Patient with Sickle Cell Disease. N Engl J Med. 2017;376:848–55.CrossRefGoogle Scholar
  34. Rocha V, Locatelli F. Searching for alternative hematopoietic stem cell donors for pediatric patients. Bone Marrow Transplant. 2008;41:207–14.CrossRefGoogle Scholar
  35. Ruggeri A, Eapen M, Scaravadou A, et al. Umbilical cord blood transplantation for children with thalassemia and sickle cell disease. Biol Blood Marrow Transplant. 2011;17:1375–82.CrossRefGoogle Scholar
  36. Saraf SL, Oh AL, Patel PR, et al. Nonmyeloablative Stem Cell Transplantation with Alemtuzumab/Low-Dose Irradiation to Cure and Improve the Quality of Life of Adults with Sickle Cell Disease. Biol Blood Marrow Transplant. 2016;22:441–8.CrossRefGoogle Scholar
  37. Taher AT, Weatherall DJ, Cappellini MD. Thalassaemia. Lancet. 2018;391:155–67.CrossRefGoogle Scholar
  38. Talano JA, Cairo MS. Hematopoietic stem cell transplantation for sickle cell disease: state of the science. Eur J Haematol. 2015;94:391–9.CrossRefGoogle Scholar
  39. Vitrano A, Calvaruso G, Lai E, et al. The era of comparable life expectancy between thalassaemia major and intermedia: Is it time to revisit the major-intermedia dichotomy? Br J Haematol. 2017;176:124–30.CrossRefGoogle Scholar
  40. Walters MC, De Castro LM, Sullivan KM, et al. Indications and results of HLA-identical sibling hematopoietic cell transplantation for sickle cell disease. Biol Blood Marrow Transplant. 2016;22:207–11.CrossRefGoogle Scholar
  41. Ware RE, Davis BR, Schultz WH, et al. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia-TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet. 2016;387:661–70.CrossRefGoogle Scholar
  42. Yawn BP, Buchanan GR, Afenyi-Annan AN, et al. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014;312:1033–48.CrossRefGoogle Scholar
  43. Yesilipek MA, Karasu G, Kaya Z, et al. A Phase II, Multicenter, Single-Arm Study to Evaluate the Safety and Efficacy of Deferasirox after Hematopoietic Stem Cell Transplantation in Children with beta-Thalassemia Major. Biol Blood Marrow Transplant. 2018;24:613–8.CrossRefGoogle Scholar

Copyright information

© EBMT and the Author(s) 2019

Open Access  This chapter is licensed under the terms of the Creative Commons Attribution 4.0 International License (, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.

The images or other third party material in this chapter are included in the chapter’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the chapter’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

Authors and Affiliations

  • Barbara Cappelli
    • 1
  • Eliane Gluckman
    • 2
    Email author
  • Khaled Ghanem
    • 3
  • Miguel R. Abboud
    • 4
  1. 1.Eurocord-Monacord, Centre Scientifique de MonacoMonacoMonaco
  2. 2.Eurocord, Department of Hematology, Hospital Saint LouisUniversity Paris-DiderotParisFrance
  3. 3.BASMA Pediatric Oncology Unit, Al Bairouni HospitalDamascusSyria
  4. 4.Department of Pediatrics and Adolescent MedicineAmerican University of Beirut Medical CenterBeirutLebanon

Personalised recommendations