Skip to main content
SpringerLink
Log in
Book cover

Gene and Cell Therapies for Beta-Globinopathies pp 59–87Cite as

Current Standards of Care and Long Term Outcomes for Thalassemia and Sickle Cell Disease

  • Chapter
  • First Online:

Part of the book series: Advances in Experimental Medicine and Biology ((ASGCT,volume 1013))

Abstract

Thalassemia and sickle cell disease (SCD) are disorders of hemoglobin that affect millions of people worldwide. The carrier states for these diseases arose as common, balanced polymorphisms during human history because they afforded protection against severe forms of malaria. These complex, multisystem diseases are reviewed here with a focus on current standards of clinical management and recent research findings. The importance of a comprehensive, multidisciplinary and lifelong system of care is also emphasized.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Chui DH, Hardison R, Riemer C, et al. An electronic database of human hemoglobin variants on the World Wide Web. Blood. 1998;91(8):2643–2644.

    CAS  PubMed  Google Scholar 

  2. Giardine B, Borg J, Viennas E, et al. Updates of the HbVar database of human hemoglobin variants and thalassemia mutations. Nucleic Acids Res. 2014;42(Database issue):D1063–9.

    Article  CAS  PubMed  Google Scholar 

  3. Laig M, Pape M, Hundrieser J, et al. The distribution of the Hb constant spring gene in Southeast Asian populations. Hum. Genet. 1990;84(2):188–190.

    Article  CAS  PubMed  Google Scholar 

  4. Voon HPJ, Vadolas J. Controlling alpha-globin: a review of alpha-globin expression and its impact on beta-thalassemia. Haematologica. 2008;93(12):1868–1876.

    Article  CAS  PubMed  Google Scholar 

  5. Pootrakul P, Sirankapracha P, Hemsorach S, et al. A correlation of erythrokinetics, ineffective erythropoiesis, and erythroid precursor apoptosis in thai patients with thalassemia. Blood. 2000;96(7):2606–2612.

    CAS  PubMed  Google Scholar 

  6. Old JM. Screening and genetic diagnosis of haemoglobin disorders. Blood Reviews. 2003;17(1):43–53.

    Article  CAS  PubMed  Google Scholar 

  7. De Sanctis V, Soliman AT, Elsedfy H, et al. Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET) position statement and guidelines. Indian J Endocrinol Metab. 2013;17(1):8–18.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cappellini MD, Cohen A. Guidelines for the management of transfusion dependent thalassemia (TDT). Thalassaemia International Federation. 2014;1–253.

    Google Scholar 

  9. Pakbaz Z, Fischer R, Fung E, et al. Serum ferritin underestimates liver iron concentration in transfusion independent thalassemia patients as compared to regularly transfused thalassemia and sickle cell patients. Pediatr. Blood Cancer. 2007;49(3):329–332.

    Article  PubMed  Google Scholar 

  10. Musallam KM, Taher AT, Cappellini, Sankaran VG. Clinical experience with fetal hemoglobin induction therapy in patients with -thalassemia. Blood. 2013;121(12):2199–2212.

    Article  CAS  PubMed  Google Scholar 

  11. Olivieri NF, Brittenham GM. Iron-chelating therapy and the treatment of thalassemia. Blood. 1997;89(3):739–761.

    CAS  PubMed  Google Scholar 

  12. Aydinok Y, Kattamis A, Viprakasit V. Current approach to iron chelation in children. British Journal of Haematology. 2014;165(6):745–755.

    Article  CAS  PubMed  Google Scholar 

  13. Carpenter JP, He T, Kirk P, Roughton M, Anderson LJ. On T2* Magnetic Resonance and Cardiac Iron. Circulation. 2011;123(14):1519–1528.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Karimi M, Musallam KM, Cappellini MD, et al. Risk factors for pulmonary hypertension in patients with β thalassemia intermedia. European Journal of Internal Medicine. 2011;22(6):607–610.

    Article  PubMed  Google Scholar 

  15. Vento S, Cainelli F, Cesario F. Infections and thalassaemia. Lancet Infect Dis. 2006;6(4):226–233.

    Article  PubMed  Google Scholar 

  16. Cunningham MJ. Complications of -thalassemia major in North America. Blood. 2004;104(1):34–39.

    Article  CAS  PubMed  Google Scholar 

  17. Vogiatzi MG, Macklin EA, Fung EB, et al. Bone disease in thalassemia: a frequent and still unresolved problem. J. Bone Miner. Res. 2009;24(3):543–557.

    Article  PubMed  Google Scholar 

  18. Voskaridou E, Terpos E. New insights into the pathophysiology and management of osteoporosis in patients with beta thalassaemia. British Journal of Haematology. 2004;127(2):127–139.

    Article  CAS  PubMed  Google Scholar 

  19. Ford JM, Rojkjaer L. Comment to: Development of lens opacities with peculiar characteristics in patients affected by thalassemia major on chelating treatment with deferasirox. Haematologica 2008;93:e9-10. Haematologica. 2008;93(6):e49–discussion e50.

    Google Scholar 

  20. Rund D, Rachmilewitz E. β-Thalassemia. N Engl J Med. 2005;353(11):1135–1146.

    Article  CAS  PubMed  Google Scholar 

  21. Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood. 2011;118(13):3479–3488.

    Article  CAS  PubMed  Google Scholar 

  22. Weatherall DJ. Phenotype|[mdash]|genotype relationships in monogenic disease: lessons from the thalassaemias. Nature Reviews Genetics. 2001;2(4):245–255.

    Article  CAS  PubMed  Google Scholar 

  23. Taher AT, Musallam KM, Karimi M, Cappellini MD. Contemporary approaches to treatment of beta-thalassemia intermedia. YBLRE. 2012;26:S24–S27.

    CAS  Google Scholar 

  24. Piomelli S, Graziano J, Karpatkin M, et al. Chelation Therapy, Transfusion Requirement, And Iron Balance In Young Thalassemic Patients*. Ann. N. Y. Acad. Sci. 1980;344(1):409–417.

    Google Scholar 

  25. Perrine SP, Ginder GD, Faller DV, et al. A Short-Term Trial of Butyrate to Stimulate Fetal-Globin-Gene Expression in the β-Globin Disorders. N Engl J Med. 1993;328(2):81–86.

    Article  CAS  PubMed  Google Scholar 

  26. Musallam KM, Sankaran VG, Cappellini MD, et al. Fetal hemoglobin levels and morbidity in untransfused patients with β-thalassemia intermedia. Blood. 2012;119(2):364–367.

    Article  CAS  PubMed  Google Scholar 

  27. Ley TJ, DeSimone J, Anagnou NP, et al. 5-azacytidine selectively increases gamma-globin synthesis in a patient with beta+ thalassemia. N Engl J Med. 1982;307(24):1469–1475.

    Article  CAS  PubMed  Google Scholar 

  28. Olivieri NF, Saunthararajah Y, Thayalasuthan V, et al. A pilot study of subcutaneous decitabine in β-thalassemia intermedia. Blood. 2011;118(10):2708–2711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Fathallah H, Taher A, Bazarbachi A, Atweh GF. Differences in response to fetal hemoglobin induction therapy in β-thalassemia and sickle cell disease. Blood Cells, Molecules, and Diseases. 2009;43(1):58–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Inati A, Kahale M, Perrine SP, et al. A phase 2 study of HQK-1001, an oral fetal haemoglobin inducer, in β-thalassaemia intermedia. British Journal of Haematology. 2014;164(3):456–458.

    Article  CAS  PubMed  Google Scholar 

  31. Singer ST, Vichinsky EP, Sweeters N, Rachmilewitz E. Darbepoetin alfa for the treatment of anaemia in alpha- or beta- thalassaemia intermedia syndromes. British Journal of Haematology. 2011;154(2):281–284.

    Article  PubMed  Google Scholar 

  32. Perrine SP, Pace BS, Faller DV. Targeted fetal hemoglobin induction for treatment of beta hemoglobinopathies. Hematology/Oncology Clinics of North America. 2014;28(2):233–248.

    Article  PubMed  Google Scholar 

  33. Platt OS, Orkin SH, Dover G, Beardsley GP. Hydroxyurea enhances fetal hemoglobin production in sickle cell anemia. Journal of Clinical …. 1984;74(2):652–656.

    Google Scholar 

  34. Karimi M, Darzi H, Yavarian M. Hematologic and Clinical Responses of Thalassemia Intermedia Patients to Hydroxyurea During 6 Years of Therapy in Iran. J. Pediatr. Hematol. Oncol. 2005;27(7):380–385.

    Article  PubMed  Google Scholar 

  35. Taher AT, Musallam KM, Karimi M, et al. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood. 2010;115(10):1886–1892.

    Article  CAS  PubMed  Google Scholar 

  36. Karimi M, Cohan N, De Sanctis V, Mallat NS, Taher A. Guidelines for Diagnosis and Management of Beta-Thalassemia Intermedia. Pediatr Hematol Oncol. 2014;31(7):583–596.

    Article  CAS  PubMed  Google Scholar 

  37. Taher A, Rassi El F, Isma’eel H, et al. Correlation of liver iron concentration determined by R2 magnetic resonance imaging with serum ferritin in patients with thalassemia intermedia. Haematologica. 2008;93(10):1584–1586.

    Article  CAS  PubMed  Google Scholar 

  38. Taher AT, Porter JB, Viprakasit V, et al. Deferasirox effectively reduces iron overload in non-transfusion-dependent thalassemia (NTDT) patients: 1-year extension results from the THALASSA study. Ann Hematol. 2013;92(11):1485–1493.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Cappellini, Robbiolo L, Bottasso BM. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia. British Journal of …. 2000;111(2):467–473.

    Google Scholar 

  40. Borgna-Pignatti C, Cappellini MD, Stefano P, et al. Survival and Complications in Thalassemia. Ann. N. Y. Acad. Sci. 2005;1054(1):40–47.

    Google Scholar 

  41. Caocci G. Health related quality of life in Middle Eastern children with beta-thalassemia. 2012;1–7.

    Google Scholar 

  42. Modell B, Khan M, Darlison M. Survival in beta-thalassaemia major in the UK: data from the UK Thalassaemia Register. The Lancet. 2000;355(9220):2051–2052.

    Article  CAS  Google Scholar 

  43. Herrick JB. Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Arch Intern Med. 1910;6:517-521.

    Article  Google Scholar 

  44. Epstein FH, Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997;337(11):762–769.

    Article  Google Scholar 

  45. Wood A, Steinberg MH. Management of sickle cell disease. N Engl J Med. 1999;340(13):1021–1030.

    Article  Google Scholar 

  46. Hoppe CC. Prenatal and newborn screening for hemoglobinopathies. Int. Jnl. Lab. Hem. 2013;35(3):297–305.

    Article  CAS  Google Scholar 

  47. Adamkiewicz TV, Sarnaik S, Buchanan GR, et al. Invasive pneumococcal infections in children with sickle cell disease in the era of penicillin prophylaxis, antibiotic resistance, and 23-valent pneumococcal polysaccharide vaccination. The Journal of Pediatrics. 2003;143(4):438–444.

    Article  PubMed  Google Scholar 

  48. Quinn CT. Sickle cell disease in childhood: from newborn screening through transition to adult medical care. Pediatric Clinics of North America. 2013;60(6):1363–1381.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Booth C, Inusa B, Obaro SK. Infection in sickle cell disease: A review. International Journal of Infectious Diseases. 2010;14(1):e2–e12.

    Article  PubMed  Google Scholar 

  50. Falletta JM, Woods GM, Verter JI, et al. Discontinuing penicillin prophylaxis in children with sickle cell anemia. Prophylactic Penicillin Study II. The Journal of Pediatrics. 1995;127(5):685–690.

    Article  CAS  PubMed  Google Scholar 

  51. McCavit TL, Quinn CT, Techasaensiri C, Rogers ZR. Increase in invasive Streptococcus pneumoniae infections in children with sickle cell disease since pneumococcal conjugate vaccine licensure. The Journal of Pediatrics. 2011;158(3):505–507.

    Article  PubMed  Google Scholar 

  52. McCavit TL, Xuan L, Zhang S, Flores G, Quinn CT. Hospitalization for invasive pneumococcal disease in a national sample of children with sickle cell disease before and after PCV7 licensure. Pediatr. Blood Cancer. 2012;58(6):945–949.

    Article  PubMed  Google Scholar 

  53. Lane PA, O'Connell JL, Lear JL, et al. Functional asplenia in hemoglobin SC disease. Blood. 1995;85(8):2238–2244.

    CAS  PubMed  Google Scholar 

  54. Zemel BS, Kawchak DA, Ohene-Frempong K, Schall JI, Stallings VA. Effects of delayed pubertal development, nutritional status, and disease severity on longitudinal patterns of growth failure in children with sickle cell disease. Pediatr. Res. 2007;61(5 Pt 1):607–613.

    Article  PubMed  Google Scholar 

  55. Platt OS, Rosenstock W, Espeland MA. Influence of sickle hemoglobinopathies on growth and development. N Engl J Med. 1984;311(1):7–12.

    Article  CAS  PubMed  Google Scholar 

  56. Rana S, Houston PE, Wang WC, et al. Hydroxyurea and growth in young children with sickle cell disease. PEDIATRICS. 2014;134(3):465–472.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Dekker LH, Fijnvandraat K, Brabin BJ, van Hensbroek MB. Micronutrients and sickle cell disease, effects on growth, infection and vaso-occlusive crisis: a systematic review. Pediatr. Blood Cancer. 2012;59(2):211–215.

    Article  PubMed  Google Scholar 

  58. Klings ES, Machado RF, Barst RJ, et al. An Official American Thoracic Society Clinical Practice Guideline: Diagnosis, Risk Stratification, and Management of Pulmonary Hypertension of Sickle Cell Disease. Am J Respir Crit Care Med. 2014;189(6):727–740.

    Article  PubMed  PubMed Central  Google Scholar 

  59. NHLBI. Evidence-based management of sickle cell disease: expert panel report, 2014. PEDIATRICS. 2014;134(6):e1775–e1775.

    Article  Google Scholar 

  60. Quinn CT, McKinstry RC, Dowling MM, et al. Acute silent cerebral ischemic events in children with sickle cell anemia. JAMA Neurol. 2013;70(1):58–65.

    Article  PubMed  PubMed Central  Google Scholar 

  61. DeBaun MR, Gordon M, McKinstry RC, et al. Controlled Trial of Transfusions for Silent Cerebral Infarcts in Sickle Cell Anemia. N Engl J Med. 2014;371(8):699–710.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Smith KE, Patterson CA, Szabo MM, Tarazi RA, Barakat LP. Predictors of academic achievement for school-age children with sickle cell disease. Advances in School Mental Health Promotion. 2013;6(1):5–20.

    Article  PubMed  PubMed Central  Google Scholar 

  63. King AA, Rodeghier MJ, Panepinto JA, et al. Silent cerebral infarction, income, and grade retention among students with sickle cell anemia. Am. J. Hematol. 2014;89(10):E188–92.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Bellet PS, Kalinyak KA, Shukla R, Gelfand MJ, Rucknagel DL. Incentive spirometry to prevent acute pulmonary complications in sickle cell diseases. N Engl J Med. 1995;333(11):699–703.

    Article  CAS  PubMed  Google Scholar 

  65. DeBaun MR, Rodeghier M, Cohen R, et al. Factors predicting future ACS episodes in children with sickle cell anemia. Am. J. Hematol. 2014;n/a–n/a.

    Google Scholar 

  66. Hulbert ML, Scothorn DJ, Panepinto JA, et al. Exchange blood transfusion compared with simple transfusion for first overt stroke is associated with a lower risk of subsequent stroke: a retrospective cohort study of 137 children with sickle cell anemia. The Journal of Pediatrics. 2006;149(5):710–712.

    Article  PubMed  Google Scholar 

  67. Scothorn DJ, Price C, Schwartz D, et al. Risk of recurrent stroke in children with sickle cell disease receiving blood transfusion therapy for at least five years after initial stroke. The Journal of Pediatrics. 2002;140(3):348–354.

    Article  PubMed  Google Scholar 

  68. Dowling MM, Quinn CT, Plumb P, et al. Acute silent cerebral ischemia and infarction during acute anemia in children with and without sickle cell disease. Blood. 2012;120(19):3891–3897.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Dowling MM, Quinn CT, Rogers ZR, Buchanan GR. Acute silent cerebral infarction in children with sickle cell anemia. Pediatr. Blood Cancer. 2010;54(3):461–464.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Bernaudin F, Verlhac S, Arnaud C, et al. Chronic, acute anemia and eICA stenosis are independent risk factors for silent cerebral infarcts in sickle cell anemia. Blood. 2014.

    Google Scholar 

  71. Adeyoju AB, Olujohungbe ABK, Morris J, et al. Priapism in sickle-cell disease; incidence, risk factors and complications - an international multicentre study. BJU Int. 2002;90(9):898–902.

    Article  CAS  PubMed  Google Scholar 

  72. Madu AJ, Ubesie A, Ocheni S, et al. Priapism in Homozygous Sickle Cell Patients: Important Clinical and Laboratory Associations. Med Princ Pract. 2014;23(3):259–263.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Siegel JF, Rich MA, Brock WA. Association of sickle cell disease, priapism, exchange transfusion and neurological events: ASPEN syndrome. J. Urol. 1993;150(5 Pt 1):1480–1482.

    Article  CAS  PubMed  Google Scholar 

  74. Smith-Whitley K. Reproductive issues in sickle cell disease. Blood. 2014;124(24):3538–3543.

    Article  CAS  PubMed  Google Scholar 

  75. Voskaridou E, Christoulas D, Bilalis A, et al. The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial (LaSHS). Blood. 2010;115(12):2354–2363.

    Article  CAS  PubMed  Google Scholar 

  76. Wang WC, Ware RE, Miller ST, et al. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011;377(9778):1663–1672.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lobo CL de C, Pinto JFC, Nascimento EM, et al. The effect of hydroxcarbamide therapy on survival of children with sickle cell disease. British Journal of Haematology. 2013;161(6):852–860.

    Google Scholar 

  78. Ware RE. How I use hydroxyurea to treat young patients with sickle cell anemia. Blood. 2010;115(26):5300–5311.

    Google Scholar 

  79. Yawn BP, Buchanan GR, Afenyi-Annan AN, et al. Management of Sickle Cell Disease. JAMA. 2014;312(10):1033.

    Article  PubMed  Google Scholar 

  80. Fu T, Corrigan NJ, Quinn CT, Rogers ZR, Buchanan GR. Minor elective surgical procedures using general anesthesia in children with sickle cell anemia without pre-operative blood transfusion. Pediatr. Blood Cancer. 2005;45(1):43–47.

    Article  PubMed  Google Scholar 

  81. Ware RE, Helms RW, SWiTCH Investigators. Stroke With Transfusions Changing to Hydroxyurea (SWiTCH). Blood. 2012;119(17):3925–3932.

    Google Scholar 

  82. Castro O, Sandler SG, Houston-Yu P, Rana S. Predicting the effect of transfusing only phenotype-matched RBCs to patients with sickle cell disease: theoretical and practical implications. Transfusion. 2002;42(6):684–690.

    Article  CAS  PubMed  Google Scholar 

  83. Quinn CT, Rogers ZR, McCavit TL, Buchanan GR. Improved survival of children and adolescents with sickle cell disease. Blood. 2010;115(17):3447–3452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Telfer P, Coen P, Chakravorty S, et al. Clinical outcomes in children with sickle cell disease living in England: a neonatal cohort in East London. Haematologica. 2007;92(7):905–912.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Emory University School of Medicine and Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, 2015 Uppergate Drive, Atlanta, GA, 30322, USA

    Satheesh Chonat

  2. Hematology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45220, USA

    Charles T. Quinn

Authors
  1. Satheesh Chonat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Charles T. Quinn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Charles T. Quinn .

Editor information

Editors and Affiliations

  1. Cincinnati Children’s Hospital, Comprehensive Sickle Cell Program, Cincinnati, Ohio, USA

    Punam Malik

  2. National Institutes of Health and Human Services, Bethesda, Maryland, USA

    John Tisdale

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media LLC

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chonat, S., Quinn, C.T. (2017). Current Standards of Care and Long Term Outcomes for Thalassemia and Sickle Cell Disease. In: Malik, P., Tisdale, J. (eds) Gene and Cell Therapies for Beta-Globinopathies. Advances in Experimental Medicine and Biology(), vol 1013. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-7299-9_3

Download citation

Publish with us

Policies and ethics

Search

Navigation