An update on thalassemia intermedia

Journal Medical Libanais

Volumn 61, Issue 3, 2013, Pages 175-182

  Maakaron, Joseph E ^a   Cappellini, Maria Domenica ^b   Taher, Ali T ^a  

^a AMERICAN UNIVERSITY OF BEIRUT   (Lebanon)

^b UNIVERSITY OF MILAN   (Italy)

Author keywords

Gene therapy; Hematopoietic stem cell transplant; Hemoglobinopathy; Ineffective erythropoiesis; Iron chelation; Iron overload; Jak2 inhibitor; Thalassemia; Thalassemia intermedia

Indexed keywords

DEFERASIROX; JANUS KINASE 2 INHIBITOR; VIRUS VECTOR; IRON CHELATING AGENT; JAK2 PROTEIN, HUMAN; JANUS KINASE 2; HEMOGLOBIN ALPHA CHAIN; HEMOGLOBIN BETA CHAIN;

BLOOD TRANSFUSION; CHOLECYSTECTOMY; ENDOCRINE DISEASE; EXTRAMEDULLARY HEMATOPOIESIS; GENE THERAPY; HEPATITIS; HUMAN; IRON CHELATION; IRON OVERLOAD; LEG ULCER; PATHOPHYSIOLOGY; PULMONARY HYPERTENSION; REVIEW; SPLENECTOMY; STEM CELL TRANSPLANTATION; THALASSEMIA INTERMEDIA; THROMBOPHILIA; ANIMAL; BETA THALASSEMIA; DEVELOPING COUNTRY; DRUG ANTAGONISM; GENETICS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; MOUSE; ARTICLE; BONE DISEASE; DRUG EFFICACY; DRUG SAFETY; ERYTHROPOIESIS; HEMOLYSIS; HYPERCOAGULABILITY; TREATMENT INDICATION; TREATMENT OUTCOME;

ANIMALS; BETA-THALASSEMIA; DEVELOPING COUNTRIES; GENETIC THERAPY; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; IRON CHELATING AGENTS; JANUS KINASE 2; MICE;

EID: 84893346077     PISSN: 00239852     EISSN: None     Source Type: Journal    
DOI: 10.12816/0001447     Document Type: Review

References (90)

1. Marengo-Rowe AJ. The thalassemias and related disorders. Proc (Bayl Univ Med Cent) 2007; 20 (1): 27-31.
2. Cooley TB, Witwer ER, Lee P. A series of cases of splenomegaly in children and peculiar changes in bones; report of cases. Am J Dis Child 1927; 34: 347-63.
3. Orkin SH, Nathan DG, Ginsburg D, Look AT: Nathan and Oski's Hematology of Infancy and Childhood, Vol. 1, E.H. Sciences, 2009.
4. Whipple GH, Bradford WL. Mediterranean disease - "thalassemia" (erythroblastic anemia of Cooley); associated pigment abnormalities simulating hemochromatosis. J Pediatr 1936; 9: 279-311.
5. Weatherall DJ. Thalassaemia: the long road from the bedside through the laboratory to the community. Transfus Med 2011; 21 (4): 218-23.
6. Weatherall DJ. The thalassemia syndromes. Tex Rep Biol Med 1980; 40: 323-33. (Pubitemid 12214025)
7. Cappellini MD, Musallam KM, Taher AT, Insight onto the pathophysiology and clinical complications of thalassemia intermedia. Hemoglobin 2009; 33 (Suppl 1): S145-S159.
8. Cappellini MD, Musallam KM, Cesaretti C, Taher A: Disorders of Erythropoiesis, Erythrocytes and Iron Metabolism, Genoa, Italy: Carole Beaumont et al., editors, Forum Service Editore, 2009.
9. Galanello R, Cao A. Relationship between genotype and phenotype. Thalassemia intermedia. Ann N Y Acad Sci 1998; 850: 325-33.
10. Weatherall DJ. Thalassaemia: the long road from bedside to genome. Nat Rev Genet 2004; 5 (8): 625-31. (Pubitemid 39005757)
11. Ho PJ, Hall GW, Luo LY, Weatherall DJ, Thein SL. Beta-thalassemia intermedia: is it possible consistently to predict phenotype from genotype? Br J Haematol 1998; 100: 70-8. (Pubitemid 28051843)
12. Rund D, Oron-Karni V, Filon D, Goldfarb A, Rachmilewitz E, Oppenheim A. Genetic analysis of beta-thalassemia intermedia in Israel: diversity of mechanisms and unpredictability of phenotype. Am J Hematol 1997; 54 (1): 16-22. (Pubitemid 27013898)
13. Phadke SR, Agarwal S. Phenotype score to grade the severity of thalassemia intermedia. Indian J Pediatr 2003; 70 (6): 477-81. (Pubitemid 36834616)
14. Olivieri NF. The beta-thalassemias. N Engl J Med 1999; 341 (2): 99-109.
15. Camaschella C, Cappellini MD. Thalassemia intermedia. Haematologica 1995; 80 (1): 58-68.
16. Taher A, Isma'eel H, Cappellini MD. Thalassemia intermedia: revisited. Blood Cells Mol Dis 2006; 37 (1): 12-20. (Pubitemid 44062361)
17. Ataga KI., Cappellini MD, Rachmilewitz EA. Beta-thalassaemia and sickle cell anaemia as paradigms of hypercoagulability. Br J Haematol 2007; 139 (1): 3-13. (Pubitemid 47389919)
18. Musallam KM, Nasreddine W, Beydoun A et al. Brain positron emission tomography in splenectomized adults with beta-thalassemia intermedia: uncovering yet another covert abnormality. Ann Hematol 2011; 35 (5-6): 530-46.
19. 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): 1886-92.
20. Taher A, Isma'eel G, Mehio G et al. Prevalence of thromboembolic events among 8,860 patients with thalassaemia major and intermedia in the Mediterranean area and Iran. Thromb Haemost 2006; 96 (4): 488-91. (Pubitemid 44560684)
21. Eldor A.Rachmilewitz EA.The hypercoagulable state in thalassemia. Blood 2002; 99 (1): 36-43.
22. Cappellini MD, Robbiolo L, Bottasso BM, Coppola R, Fiorelli G, Mannucci AP. Venous thromboembolism and hypercoagulability in splenectomized patients with thalassaemia intermedia. Br J Haematol 2000; 111 (2); 467-73. (Pubitemid 32009338)
23. Taher AT, Otrock ZK, Uthman I, Cappellini MD. Thalassemia and hypercoagulability. Blood Rev 2008; 22 (5): 283-92.
24. Taher AT, Musallam KM, El-Beshlawy A et al. Age-related complications in treatment-naive patients with thalassaemia intermedia. Br J Haematol 2010; 150 (4): 486-9.
25. El-Beshlawy A, Youssry I, El-Saidi S et al. Pulmonary hypertension in beta-thalassemia major and the role of L-camitine therapy. Pediatr Hematol Oncol 2008; 25 (8): 734-43.
26. Taher AT, Musallam KM, Nasreddine W, Beydoun A. Covert brain ischaemia in splenectomised adults with thalassemia intermedia: An emerging entity. Thromb Haemost 2010; 104 (3): 652-3.
27. Nemeth E, Tuttle MS, Powelson J et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004; 306 (5704): 2090-3. (Pubitemid 40007660)
28. Taher A, Hershko C, Cappellini MD. Iron overload in thalassaemia intermedia: reassessment of iron chelation strategies. Br J Haematol 2009; 147 (5): 634-40.
29. Pakbaz Z, Fischer R, Fung E, Nielsen P, Harmatz P, Vichinsky E. 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): 329-32. (Pubitemid 47236225)
30. Taher AT, Musallam KM, Cappellini MD, Weatherall DJ. Optimal management of beta thalassaemia intermedia. Br J Haematol 2011; 152 (5): 512-23.
31. Cappellini MD, Motta I, Musallam KM, Taher AT. Redefining thalassemia as a hypercoagulable state. Ann N Y Acad Sci 2010; 1202: 231-6.
32. Chehal A, Aoun E, Koussa S, Skoury H, Taher A. Hypertransfusion: a successful method of treatment in thalassemia intermedia patients with spinal cord compression secondary to extra-medullary hematopoiesis. Spine (Phila Pa 1976) 2003; 28 (13): E245-E249.
33. Castelli R, Graziadei G, Karimi M, Cappellini MD. Intrathoracic masses due to extramedullary hematopoiesis. Am J Med Sci 2004; 328 (5): 299-303. (Pubitemid 39518536)
34. Saxon BR, Rees D, Olivieri NF. Regression of extramedullary haemopoiesis and augmentation of fetal haemoglobin concentration during hydroxyurea therapy in beta thalassaemia. Br J Haematol 1998; 101 (3): 416-19. (Pubitemid 28266931)
35. Cario H, Wegener M, Debatin KM, Kohne E. Treatment with hydroxyurea in thalassemia intermedia with paravertebral pseudotumors of extramedullary hematopoiesis. Ann Hematol 2002; 81 (8): 478-82. (Pubitemid 36067664)
36. Gladwin MT, Sachdev V, Jison ML et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 2004; 350 (9): 886-95. (Pubitemid 38252536)
37. Isma'eel H, Chafic AH, Rassi FE et al. Relation between iron-overload indices, cardiac echo-Doppler, and biochemical markers in thalassemia intermedia. Am J Cardiol 2008; 102 (3): 363-7.
38. Morris CR, Vichinsky EP. Pulmonary hypertension in thalassemia. Ann N Y Acad Sci 2010; 1202: 205-13.
39. Sonakul D, Pacharee P, Thakerngpol K. Pathologic findings in 76 autopsy cases of thalassemia. Birth Defects Orig Artic Ser 1988; 23 (5B): 157-76.
40. Morris CR, Gladwin MT, Kato GJ. Nitric oxide and arginine dysregulation: a novel pathway to pulmonary hypertension in hemolytic disorders. Curr Mol Med 2008; 8 (7): 620-32.
41. Aessopos A, Farmakis D, Deftereos S et al. Thalassemia heart disease: a comparative evaluation of thalassemia major and thalassemia intermedia. Chest 2005; 127 (5): 1523-30. (Pubitemid 46218775)
42. Hahalis G, Alexopoulos D, Kremastinos DT, Zoumbos NC. Heart failure in beta-thalassemia syndromes: a decade of progress. Am J Med 2005; 118 (9): 957-67. (Pubitemid 41297756)
43. Morris CR. Mechanisms of vasculopathy in sickle cell disease and thalassemia. Hematology Am Soc Hematol Educ Program 2008; 177-85.
44. Singer ST, Kuypers FA, Styles L, Vichinsky EP, Foote D, Rosenfeld H. Pulmonary hypertension in thalassemia: association with platelet activation and hypercoagulable state. Am J Hematol 2006; 81 (9): 670-5. (Pubitemid 44306825)
45. Morris CR. Pulmonary hypertension in thalassemia assessed by echocardiography: a report from base-line data of the thalassemia clinical research network Longitudinal Cohort Study. Blood 2009; 114: 796 [abst 2016].
46. Hagar RW, Morris CR, Vichinsky EP. Pulmonary hypertension in thalassaemia major patients with normal left ventricular systolic function. Br J Haematol 2006; 133 (4): 433-5.
47. Mokhtar GM, Adly AA, El Alfy MS, Tawfik LM, Khairy AT. N-terminal natriuretic peptide and ventilation-perfusion lung scan in sickle cell disease and thalassemia patients with pulmonary hypertension. Hemoglobin 2010; 34 (1): 78-94.
48. Morris CR. Role of arginase in sickle cell lung disease and hemolytic anemias. Open Nitric Oxide J 2010; 2: 41-54.
49. Setty BN, Betal SG, Zhang J, Stuart MJ. Heme induces endothelial tissue factor expression: potential role in hemostatic activation in patients with hemolytic anemia. J Thromb Haemost 2008; 6 (12): 2202-9.
50. Zakynthinos E, Vassilakopoulos T, Kaltsas P et al. Pulmonary hypertension, interstitial lung fibrosis, and lung iron deposition in thalassaemia major. Thorax 2001; 56 (9): 737-9. (Pubitemid 32831703)
51. Karimi M, Borzouee M, Mehrabani A, Cohan N. Echocardiographic finding in beta-thalassemia intermedia and major: absence of pulmonary hypertension following hydroxyurea treatment in beta-thalassemia intermedia. Eur J Haematol 2009; 82 (3): 213-18.
52. Derchi G, Forni GL, Formisano F et al. Efficacy and safety of sildenafil in the treatment of severe pulmonary hypertension in patients with hemoglobinopathies. Haematologica 2005; 90 (4): 452-8. (Pubitemid 40592887)
53. Littera R, La Nasa G, Derchi G, Cappellini MD, Chang CY, Contu L. Long-term treatment with sildenafil in a thalassemic patient with pulmonary hypertension. Blood 2002; 100(4): 1516-17. (Pubitemid 34864323)
54. Gupta VL, Choubey BS. RBC survival, zinc deficiency, and efficacy of zinc therapy in sickle cell disease. Birth Defects Orig Artic Ser 1987; 23 (5A): 477-83.
55. al-Momen AK. Recombinant human erythropoietin induced rapid healing of a chronic leg ulcer in a patient with sickle cell disease. Acta Haematol 1991; 86 (1): 46-8.
56. Mancuso A. Hepatocellular carcinoma in thalassemia: A critical review. World J Hepato 2010; 2 (5): 171-4.
57. Spanos T, Karageorga M, Ladis V, Peristeri J, Hatziliami A, Kattamis C. Red cell alloantibodies in patients with thalassemia. Vox Sang 1990; 58 (1): 50-5. (Pubitemid 20042996)
58. Hmida S, Mojaat N, Maamar M, Bejaoui M, Mediouni M, Boukef K. Red cell alloantibodies in patients with haemoglobinopathies. Nouv Rev Fr Hematol 1994; 36 (5): 363-6. (Pubitemid 24352497)
59. Pippard MJ, Callender ST, Finch CA. Ferrioxamine excretion in iron-loaded man. Blood 1982; 60 (2): 288-94. (Pubitemid 12048669)
60. Federation TI. Guidelines for the clinical management of thalassemia. 2004. Available from: http://www.thalassaemia.org/cy/Publications/htm
61. Musallam KM, Cappellini MD, Wood JC et al. Elevated liver iron concentration is a marker of increased morbidity in patients with {beta} thalassemia intermedia. Haematologica 2011; 96 (11): 1605-12.
62. Treadwell MJ, Weissman L. Improving adherence with deferoxamine regimens for patients receiving chronic transfusion therapy. Semin Hematol 2001; 38 (1 Suppl 1): 77-84. (Pubitemid 32110276)
63. Cappellini MD. Overcoming the challenge of patient compliance with iron chelation therapy. Semin Hematol 2005; 42 (2 Suppl 1):S19-S21. (Pubitemid 40410480)
64. Cossu P, Toccafondi C, Vardeu F et al. Iron overload and desferrioxamine chelation therapy in beta-thalassemia intermedia. Eur J Pediatr 1981; 137 (3): 267-71. (Pubitemid 12235800)
65. Taher AT, Porter J, Viprakasit V et al. Deferasirox reduces iron overload significantly in nontransfusion-dependent thalassemia: 1-year results from a prospective, randomized, double-blind, placebo-controlled study. Blood 2012; 120 (5): 970-7.
66. Rienhoff H Y Jr, Viprakasit V, Tay L et al. A phase 1 dose-escalation study: safety, tolerability, and pharmacokinetics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload. Haematologica 2011; 96 (4): 521-5.
67. Krishnamurti L, Bunn HF, Williams AM, Tolar J. Hematopoietic cell transplantation for hemoglobinopathies. Curr Probl Pediatr Adolesc Health Care 2008; 38 (1): 6-18. (Pubitemid 350194044)
68. Lucarelli G, Galimberti M, Polchi P et al. Bone marrow transplantation in patients with thalassemia. N Engl J Med 1990; 322 (7): 417-21. (Pubitemid 20059509)
69. Pinto FO, Roberts I. Cord blood stem cell transplantation for haemoglobinopathies. Br J Haematol 2008; 141 (3): 309-24. (Pubitemid 351521145)
70. Smiers FJ, Krishnamurti L, Lucarelli G. Hematopoietic stem cell transplantation for hemoglobinopathies: current practice and emerging trends. Pediatr Clin North Am 2010; 57 (1): 181-205.
71. Dini G, Lanino E, Lamparelli T et al. Unrelated donor marrow transplantation: initial experience of the Italian bone marrow transplant group (GITMO). Bone Marrow Transplant 1996; 17 (1): 55-62. (Pubitemid 26031891)
72. La Nasa G, Giardini C, Argiolu F et al. Unrelated donor bone marrow transplantation for thalassemia: the effect of extended haplotypes. Blood 2002; 99 (12): 4350-6. (Pubitemid 34627200)
73. Yannaki E, Emery DW, Stamatoyannopoulos G. Gene therapy for beta-thalassaemia: the continuing challenge. Expert Rev Mol Med 2010; 12: e31.
74. Boncimino A, Bertaina A, Locatelli F. Cord blood transplantation in patients with hemoglobinopathies. Transfus Apher Sci 2010; 42 (3): 277-81.
75. Hall JG, Martin PL, Wood S, Kurtzberg J. Unrelated umbilical cord blood transplantation for an infant with beta-thalassemia major. J Pediatr Hematol Oncol 2004; 26 (6): 382-5. (Pubitemid 38747730)
76. Jaing TH, Hung IJ, Yang CP, Chen SH, Sun CF, Chow R. Rapid and complete donor chimerism after unrelated mismatched cord blood transplantation in 5 children with beta-thalassemia major. Biol Blood Marrow Transplant 2005; 11 (5): 349-53. (Pubitemid 40542927)
77. Gaszner M. Felsenfeld G. Insulators: exploiting transcriptional and epigenetic mechanisms. Nat Rev Genet 2006; 7 (9): 703-13. (Pubitemid 44260006)
78. May C, Rivella S, Chadburn A, Sadelain M. Successful treatment of murine beta-thalassemia intermedia by transfer of the human beta-globin gene. Blood 2002; 99 (6): 1902-8. (Pubitemid 34525467)
79. Hacein-Bey-Abina S, Von Kalle C, Schmidt M et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 2003; 302 (5644): 415-19. (Pubitemid 37296260)
80. Hacein-Bey-Abina S, Hauer J, Lim A et al. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med 2010; 363 (4): 355-64.
81. Imren S, Payen E, Westerman KA et al. Permanent and panerythroid correction of murine beta thalassemia by multiple lentiviral integration in hematopoietic stem cells. Proc Natl Acad Sci U S A 2002; 99 (22): 14380-5. (Pubitemid 35257680)
82. May C, Rivella S, Callegari J et al. Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin. Nature 2000; 406 (6791): 82-6. (Pubitemid 30460215)
83. Persons DA, Hargrove PW, Allay ER, Hanawa H, Nienhuis AW. The degree of phenotypic correction of murine beta-thalassemia intermedia following lentiviral-mediated transfer of a human gamma-globin gene is influenced by chromosomal position effects and vector copy number. Blood 2003; 101 (6): 2175-83. (Pubitemid 36302055)
84. Cavazzana-Calvo M, Payen E, Negre O et al. Transfusion independence and HMGA2 activation after gene therapy of human beta-thalassaemia. Nature 2010; 467 (7313): 318-22.
85. Kaiser J. Gene therapy. Beta-thalassemia treatment succeeds, with a caveat. Science 2009; 326 (5959): 1468-9.
86. Takahashi K, Tanabe K, Ohnuki M et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131 (5): 861-72. (Pubitemid 350138099)
87. Takahashi K, Okita K, Nakagawa M, Yamanaka S. Induction of pluripotent stem cells from fibroblast cultures. Nat Protoc 2007; 2 (12): 3081-9.
88. Taher A, Mehio G, Isma'eel H, Cappellini MD. Stroke in thalassemia: a dilemma. Am J Hematol 2008; 83 (4): 343. (Pubitemid 351458020)
89. Rivella S. Ineffective erythropoiesis and thalassemias. Curr Opin Hematol 2009; 16 (3): 187-94.
90. Libani IV, Guy EC, Melchiori L et al. Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia. Blood 2008; 112 (3): 875-85.