Thalassemia 2016: Modern medicine battles an ancient disease

American Journal of Hematology

Volumn 91, Issue 1, 2016, Pages 15-21

  Rund, Deborah ^a  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

DEFEROXAMINE; HEAT SHOCK PROTEIN 70; HEMOGLOBIN; HEMOGLOBIN ALPHA CHAIN; HEMOGLOBIN BETA CHAIN; HEMOGLOBIN F; HEPCIDIN; JANUS KINASE 2 INHIBITOR; LUSPATERCEPT; MESSENGER RNA; SOTATERCEPT; ACTIVIN RECEPTOR; DNA; GLOBIN; JAK2 PROTEIN, HUMAN; JANUS KINASE 2;

ALLOIMMUNIZATION; AMNIOCENTESIS; ARTICLE; BETA THALASSEMIA; BLOOD TRANSFUSION; BONE MARROW TRANSPLANTATION; CHELATION THERAPY; CHORION VILLUS SAMPLING; DNA MODIFICATION; GENETIC COUNSELING; HEMOGLOBIN E-BETA THALASSEMIA; HEMOGLOBIN H DISEASE; HUMAN; HYPERCOAGULABILITY; IRON CHELATION; IRON OVERLOAD; MACROPHAGE; NEXT GENERATION SEQUENCING; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); POINT MUTATION; PRENATAL DIAGNOSIS; PRIORITY JOURNAL; QUALITY OF LIFE; REDUCED INTENSITY CONDITIONING; SINGLE NUCLEOTIDE POLYMORPHISM; TARGET CELL; THALASSEMIA; VIRAL GENE THERAPY; ANIMAL; ANTAGONISTS AND INHIBITORS; BLOOD; GENE THERAPY; GENETIC SCREENING; GENETICS; METABOLISM; MORTALITY;

ACTIVIN RECEPTORS; ANIMALS; BLOOD TRANSFUSION; BONE MARROW TRANSPLANTATION; DNA; GENETIC TESTING; GENETIC THERAPY; GLOBINS; HUMANS; JANUS KINASE 2; QUALITY OF LIFE; THALASSEMIA;

EID: 84954304677     PISSN: 03618609     EISSN: 10968652     Source Type: Journal    
DOI: 10.1002/ajh.24231     Document Type: Article

References (88)

1. Cooley T, Lee P. A series of cases of splenomegaly in children with anemia and peculiar bone changes. Trans Am Pediatr 1925;37:29.
2. Angel JL. Porotic hyperostosis, anemias, malarias, and marshes in the prehistoric Eastern Mediterranean. Science 1966;153:760-763.
3. Filon D, Faerman M, Smith P, Oppenheim A. Sequence analysis reveals a beta-thalassaemia mutation in the DNA of skeletal remains from the archaeological site of Akhziv, Israel. Nat Genet 1995;9:365-368.
4. Nienhuis AW, Anderson WF. Isolation and translation of hemoglobin messenger RNA from thalassemia, sickle cell anemia, and normal human reticulocytes. J Clin Invest 1971;50:2458-2460.
5. Kacian DL, Gambino R, Dow LW, et al. Decreased globin messenger RNA in thalassemia detected by molecular hybridization. Proc Natl Acad Sci USA 1973;70:1886-1890.
6. Saiki RK, Bugawan TL, Horn GT, et al. Analysis of enzymatically amplified beta-globin and HLA-DQ alpha DNA with allele-specific oligonucleotide probes. Nature 1986;324:163-166.
7. Hardison RC, Chui DH, Giardine B, et al. HbVar: A relational database of human hemoglobin variants and thalassemia mutations at the globin gene server. Hum Mutat 2002;19:225-233.
8. 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:D1063-D1069. doi:10.1093/nar/gkt911
9. Wainscoat JS, Thein SL, Weatherall DJ. Thalassaemia intermedia. Blood Rev 1987;1:273-279.
10. Rund D, Rachmilewitz EA. Beta thalassemia. N Engl J Med 2005;353:1135-1146.
11. Weatherall DJ. The definition and epidemiology of non-transfusion-dependent thalassemia. Blood Rev 2012;26:S3-S6.
12. Cao A. Results of programmes for antenatal detection of thalassemia in reducing the incidence of the disorder. Blood Rev 1987;1:169-176.
13. Chiu RW, Lau TK, Leung TN, et al. Prenatal exclusion of beta thalassaemia major by examination of maternal plasma. Lancet 2002;360:998-1000.
14. Papasavva T, van Ijcken WF, Kockx CE, et al. Next generation sequencing of SNPs for non-invasive prenatal diagnosis: Challenges and feasibility as illustrated by an application to β-thalassaemia. Eur J Hum Genet 2013;21:1403-1410.
15. Berger VK, Baker VL. Preimplantation diagnosis for single gene disorders. Semin Reprod Med 2014;32:107-113.
16. Cao A, Kan YW. Prevention of thalassemia. Cold Spring Harb Perspect Med. 2013;3:a011775.
17. Ray PF, Kaeda JS, Bingham J, et al. Preimplantation genetic diagnosis of beta-thalassaemia major. Lancet 1996;347:1696.
18. Traeger-Synodinos J. Preimplantation genetic diagnosis, an alternative to conventional prenatal diagnosis of the hemoglobinopathies. Int J Lab Hematol 2013;35:571-579.
19. Dickens BM. Preimplantation genetic diagnosis and 'savior siblings.' Int J Gynaecol Obstet 2005;88:91-96.
20. Thein SL, Sampietro M, Rohde K, et al. Detection of a major gene for heterocellular hereditary persistence of fetal hemoglobin after accounting for genetic modifiers. Am J Hum Genet 1994;54:214-228.
21. Rund D, Oron-Karni V, Filon D, et al. Genetic analysis of beta-thalassemia intermedia in Israel: Diversity of mechanisms and unpredictability of phenotype. Am J Hematol 1997;54:16-22.
22. Thein SL. Genetic association studies in β-hemoglobinopathies. Hematology Am Soc Hematol Educ Program 2013;2013:354-361.
23. Menzel S, Garner C, Gut I, et al. A QTL influencing F cell production maps to a gene encoding a zinc-finger protein on chromosome 2p15. Nat Genet 2007;39:1197-1199.
24. Uda M, Galanello R, Sanna S, et al. Genome-wide association study shows BCL11A associated with persistent fetal hemoglobin and amelioration of the phenotype of beta-thalassemia. Proc Natl Acad Sci USA 2008;105:1620-1625.
25. Smith CH, Schulman I, Ando RE, Stern G. Studies in Mediterranean (Cooley's) anemia. II. The suppression of hematopoiesis by transfusions. Blood 1955;10:707-717.
26. Vichinsky E, Neumayr L, Trimble S, et al. Transfusion complications in thalassemia patients: A report from the Centers for Disease Control and Prevention (CME). Transfusion 2014;54:972-981.
27. Goss C, Giardina P, Degtyaryova D, et al. Red blood cell transfusions for thalassemia: Results of a survey assessing current practice and proposal of evidence-based guidelines. Transfusion 2014;54:1773-1781.
28. Borgna-Pignatti C, Garani MC, Forni GL, et al. Hepatocellular carcinoma in thalassaemia: An update of the Italian Registry. Br J Haematol 2014;167:121-126.
29. Romano C, Massimo L, Tortorolo G. Preliminary note on the therapeutic use of desferrioxamine in Cooley's Disase. Minerva Pediatr 1964;16:711-713.
30. Smith RS. Chelating agents in the diagnosis and treatment of iron overload in thalassemia. Ann NY Acad Sci 1964;119:776-788.
31. Brittenham GM, Griffith PM, Nienhuis AW, et al. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 1994;331:567-573.
32. Grady RW. The development of new drugs for use in iron chelation therapy. Birth Defects Orig Artic Ser 1976;12:161-175.
33. Aydinok Y, Kattamis A, Viprakasit V. Current approach to iron chelation in children. Br J Haematol 2014;745-755.
34. Sheth S. Iron chelation: An update. Curr Opin Hematol 2014;21:179-185.
35. Link G, Konijn AM, Breuer W, et al. Exploring the "iron shuttle" hypothesis in chelation therapy: Effects of combined deferoxamine and deferiprone treatment in hypertransfused rats with labeled iron stores and in iron-loaded rat heart cells in culture. J Lab Clin Med 2001;138:130-138.
36. Vlachodimitropoulou Koumoutsea E, Garbowski M, Porter J. Synergistic intracellular iron chelation combinations: mechanisms and conditions for optimizing iron mobilization. Br J Haematol 2015;170:874-883.
37. Piga A, Longo F, Musallam KM, et al. Assessment and management of iron overload in β-thalassaemia major patients during the 21st century: A real-life experience from the Italian WEBTHAL project. Br J Haematol 2013;161:872-883.
38. Olivieri NF, Nathan DG, MacMillan JH, et al. Survival in medically treated patients with homozygous beta-thalassemia. N Engl J Med 1994;331:574-578.
39. Puliyel M, Sposto R, Berdoukas VA, et al. Ferritin trends do not predict changes in total body iron in patients with transfusional iron overload. Am J Hematol 2014;89:391-394.
40. Wood JC. Estimating tissue iron burden: current status and future prospects. Br J Haematol 2015;170:15-28.
41. Sarigianni M, Liakos A, Vlachaki E, et al. Accuracy of magnetic resonance imaging in diagnosis of liver iron overload: A systematic review and meta-analysis. Clin Gastroenterol Hepatol 2015;13:55-63.e5.
42. 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.
43. Eldor Lellouche F, Goldfarb A, et al. In vivo platelet activation in beta-thalassemia major reflected by increased platelet-thromboxane urinary metabolites. Blood 1991;77:1749-1753.
44. Cappellini MD, Robbiolo L, Bottasso BM, et al. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia. Br J Haematol 2000;111:467-473.
45. Cappellini MD, Poggiali E, Taher AT, Musallam KM. Hypercoagulability in β-thalassemia: A status quo. Expert Rev Hematol 2012;5:505-511.
46. Musallam KM, Taher AT, Karimi M, Rachmilewitz EA. Cerebral infarction in β-thalassemia intermedia: Breaking the silence. Thromb Res 2012;130:695-702.
47. Haines D, Martin M, Carson S, et al. Pain in thalassaemia: The effects of age on pain frequency and severity. Br J Haematol 2013;160:680-687.
48. Wong P, Fuller PJ, Gillespie MT, et al. Thalassemia bone disease: A 19-year longitudinal analysis. J Bone Miner Res 2014;29:2468-2473.
49. Tsay J, Yang Z, Ross FP, et al. Bone loss caused by iron overload in a murine model: Importance of oxidative stress. Blood 2010;116:2582-2589.
50. De Sanctis V, Soliman AT, Elsedfy H, et al. Osteoporosis in thalassemia major: An update and the I-CET 2013 recommendations for surveillance and treatment. Pediatr Endocrinol Rev 2013;11:167-180.
51. Giusti A. Bisphosphonates in the management of thalassemia-associated osteoporosis: A systematic review of randomised controlled trials. J Bone Miner Metab 2014;32:606-615.
52. Nemtsas P, Arnaoutoglou M, Perifanis V, et al. Neurological complications of beta-thalassemia. Ann Hematol 2015;94:1261-1265.
53. Gaziev J, Sodani P, Lucarelli G. Hematopoietic stem cell transplantation in thalassemia. Bone Marrow Transplant 2008;42:S41
54. Gaziev J, Isgrò A, Sodani P, et al. Optimal outcomes in young class 3 patients with thalassemia undergoing HLA-identical sibling bone marrow transplantation. Transplantation, in press.
55. Mathews V, Savani BN. Conditioning regimens in allo-SCT for thalassemia major. Bone Marrow Transplant 2014;49:607-610.
56. Kharbanda S, Smith AR, Hutchinson SK, et al. Unrelated donor allogeneic hematopoietic stem cell transplantation for patients with hemoglobinopathies using a reduced-intensity conditioning regimen and third-party mesenchymal stromal cells. Biol Blood Marrow Transplant 2014;20:581-586.
57. King AA, Kamani N, Bunin N, et al. Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies. Am J Hematol, in press. doi: 10.1002/ajh.24183.
58. 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;122:2751-2756.
59. Parikh SH, Mendizabal A, Benjamin CL, et al. A novel reduced-intensity conditioning regimen for unrelated umbilical cord blood transplantation in children with nonmalignant diseases. Biol Blood Marrow Transplant 2014;20:326-336.
60. Faulkner LB, Uderzo C, Masera G. International cooperation for the cure and prevention of severe hemoglobinopathies. J Pediatr Hematol Oncol 2013;35:419-423.
61. Mehta PA, Faulkner LB. Hematopoietic cell transplantation for thalassemia: A global perspective BMT tandem meeting 2013. Biol Blood Marrow Transplant 2013;19:S70-S73.
62. Sankaran VG, Weiss MJ. Anemia: Progress in molecular mechanisms and therapies. Nat Med 2015;21:221-230.
63. Rivella S. βthalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies. Haematologica 2015;100:418-430.
64. Ngo DA, Steinberg MH. Genomic approaches to identifying targets for treating β-hemoglobinopathies. BMC Med Genomics 2015;8:44-57.
65. Musallam KM, Taher AT, Cappellini MD, Sankaran VG. Clinical experience with fetal hemoglobin induction therapy in patients with β-thalassemia. Blood 2013;121:2199-2212.
66. Bauer DE, Kamran SC, Lessard S, et al. An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science 2013;342:253-257.
67. McPherron AC. Metabolic functions of myostatin and GDF11. Immunol Endocr Metab Agents Med Chem 2010;10:217-231.
68. Ruckle J, Jacobs M, Kramer W, et al. Single-dose, randomized, double-blind, placebo-controlled study of ACE-011 (ActRIIA-IgG1) in postmenopausal women. J Bone Miner Res 2009;24:744-752.
69. Dussiot M, Maciel TT, Fricot A, et al. An activin receptor IIA ligand trap corrects ineffective erythropoiesis in β-thalassemia. Nat Med 2014;20:398-407.
70. Nemeth E. Hepcidin and β-thalassemia major. Blood 2013;122:3-4.
71. Attie KM, Allison MJ, McClure T, et al. A phase 1 study of ACE-536, a regulator of erythroid differentiation, in healthy volunteers. Am J Hematol 2014;89:766-770.
72. Piga AG, Perrotta S, Melpignano A, et al. ACE-536 Increases hemoglobin and decreases transfusion burden and serum ferritin in adults with beta-thalassemia: Preliminary results from a phase 2 study. Blood 2014;124:53a.
73. Rivella S. Ineffective erythropoiesis and thalassemias. Curr Opin Hematol 2009;16:187-94.
74. Libani IV, Guy EC, Melchiori L, et al. Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia. Blood 2008;112:875-885.
75. Manwani D, Bieker JJ. The erythroblastic island. Curr Top Dev Biol 2008;82:23-53.
76. Ginzburg Y, Rivella S. βthalassemia: A model for elucidating the dynamic regulation of ineffective erythropoiesis and iron metabolism. Blood 2011;118:4321-4330.
77. Ramos P, Casu C, Gardenghi S, et al. Macrophages support pathological erythropoiesis in polycythemia vera and β-thalassemia. Nat Med 2013;19:437-445.
78. Jacobsen RN, Perkins AC, Levesque JP. Macrophages and regulation of erythropoiesis. Curr Opin Hematol 2015;22:212-219.
79. Yuan J, Angelucci E, Lucarelli G, et al. Accelerated programmed cell death (apoptosis) in erythroid precursors of patients with severe beta-thalassemia (Cooley's anemia). Blood 1993;82:374-377.
80. Arlet JB, Ribeil JA, Guillem F, et al. HSP70 sequestration by free α-globin promotes ineffective erythropoiesis in β-thalassaemia. Nature 2014;514:242-246.
81. Ghosh S, Thrasher AJ, Gaspar HB. Gene therapy for monogenic disorders of the bone marrow. Br J Haematol, in press. doi: 10.1111/bjh.13520.
82. Cavazzana-Calvo M, Payen E, Negre O, et al. Transfusion independence and HMGA2 activation after gene therapy of human β-thalassaemia. Nature 2010;467:318-322.
83. Cavazzana M, Ribeil JA, Payen E, et al. Outcomes of gene therapy for β-thalassemia major and severe sickle cell disease via transplantation of autologous hematopoietic stem cells transduced ex vio with a lentiviral beta globin vector. Haematologica 2014;99:S466.
84. Finotti A, Breda L, Lederer CW, et al. Recent trends in the gene therapy of β-thalassemia. J Blood Med 2015;6:69-85.
85. Genovese P, Schiroli G, Escobar G, et al. Targeted genome editing in human repopulating haematopoietic stem cells. Nature 2014;510:235-240.
86. Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 2008;86:480-487.
87. Telfer P. Update on survival in thalassemia major. Hemoglobin 2009;33:S76-S80.
88. Weatherall DJ. The challenge of haemoglobinopathies in resource-poor countries. Br J Haematol 2011;154:736-744.