Clinical hemoglobinopathies: Iron, lungs and new blood

Current Opinion in Hematology

Volumn 13, Issue 6, 2006, Pages 407-418

  Morris, Claudia R ^a   Singer, Sylvia T ^a   Walters, Mark C ^a  

^a CHILDREN S HOSPITAL OAKLAND   (United States)

Author keywords

Bone marrow transplantation; Iron chelation therapy; Pulmonary hypertension; Sickle cell anemia; Thalassemia major

Indexed keywords

AMINOTRANSFERASE; ARGININE; AZATHIOPRINE; BUSULFAN; CHELATING AGENT; CREATININE; CYCLOPHOSPHAMIDE; DEFERASIROX; DEFEROXAMINE MESYLATE; FLUDARABINE; HYDROXYUREA; IMMUNOSUPPRESSIVE AGENT; IRON; NITRIC OXIDE; SILDENAFIL; THIOTEPA; THYMOCYTE ANTIBODY;

ABNORMALLY HIGH SUBSTRATE CONCENTRATION IN BLOOD; AGRANULOCYTOSIS; ARTHROPATHY; BLOOD; BONE DEFECT; CHONDROPATHY; CLINICAL TRIAL; ERYTHROCYTE TRANSFUSION; GASTROINTESTINAL SYMPTOM; GRAFT VERSUS HOST REACTION; HEART DEATH; HEMATOPOIESIS; HEMOGLOBINOPATHY; HEMOLYSIS; HUMAN; HYPOACUSIS; IRON OVERLOAD; LUNG; LUNG DISEASE; NEUTROPENIA; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RASH; RETINA DISEASE; REVIEW; SICKLE CELL ANEMIA; THALASSEMIA; THALASSEMIA MAJOR; ZINC DEFICIENCY;

ANEMIA, SICKLE CELL; ARGININE; BETA-THALASSEMIA; CHILD; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; HYPERTENSION, PULMONARY; IRON CHELATING AGENTS; IRON OVERLOAD; PROGNOSIS;

EID: 33750223115     PISSN: 10656251     EISSN: 15317048     Source Type: Journal    
DOI: 10.1097/01.moh.0000245685.24462.4e     Document Type: Review

References (121)

1. Esposito BP, Breuer W, Sirankapracha P, et al. Labile plasma iron in iron overload: redox activity and susceptibility to chelation. Blood 2003; 102:2670-2677.
2. Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR. Complications of beta-thalassemia major in North America. Blood 2004; 104:34-39.
3. Borgna-Pignatti C, Cappellini MD, De Stefano P, et al. Survival and complications in thalassemia. Ann N Y Acad Sci 2005; 1054:40-47.
4. Pennell DJ. T2* magnetic resonance and myocardial iron in thalassemia. Ann N Y Acad Sci 2005; 1054:373-378.
5. Fischer R, Piga A, Harmatz P, Nielsen P. Monitoring long-term efficacy of iron chelation treatment with biomagnetic liver susceptometry. Ann N Y Acad Sci 2005; 1054:350-357.
6. St Pierre TG, Clark PR, Chua-anusorn W, et al. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood 2005; 105:855-861. An important development in noninvasive measurement of LIC. Results of liver iron by biopsy are compared to the results obtained by R2 MRI technology in over 100 patients.
7. Wood JC, Enriquez C, Ghugre N, et al. MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients. Blood 2005; 106:1460-1465. This study analyzes R2 and R2* MRI methods for measurement of LICs, and correlates them to results by liver biopsy in 22 of 102 patients' analyzed. Both techniques show very close correlation. This article provides important data for noninvasive analysis of LIC in the future.
8. Cohen AR, Galanello R, Piga A, et al. Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone. Blood 2003; 102:1583-1587.
9. Peng CT, Wu KH, Wu SF, et al. Deferiprone or deferoxamine vs. combination therapy in patients with beta-thalassemia major: a case study in Taiwan. Hemoglobin 2006; 30:125-130.
10. Pootrakul P, Sirankapracha P, Sankote J, et al. Clinical trial of deferiprone iron chelation therapy in beta-thalassaemia/haemoglobin E patients in Thailand. Br J Haematol 2003; 122:305-310.
11. Taher A, Aoun E, Sharara AI, et al. Five-year trial of deferiprone chelation therapy in thalassaemia major patients. Acta Haematol 2004; 112:179-183.
12. Piga A, Gaglioti C, Fogliacco E, Tricta F. Comparative effects of deferiprone and deferoxamine on survival and cardiac disease in patients with thalassemia major: a retrospective analysis. Haematologica 2003; 88:489-496.
13. Borgna-Pignatti C, Cappellini MD, De Stefano P, et al. Cardiac morbidity and mortality in deferoxamine- or deferiprone-treated patients with thalassemia major. Blood 2006; 107:3733-3737. Cardiac events in over 500 patients who received only Desferal or switched from Desferal to deferiprone are compared. Although unmatched groups are analyzed in a retrospective manner, the results are carefully analyzed and provide strong clinical data.
14. Pennell DJ, Berdoukas V, Karagiorga M, et al. Randomized controlled trial of deferiprone or deferoxamine in beta-thalassemia major patients with asymptomatic myocardial siderosis. Blood 2006; 107:3738-3744. A prospective trial comparing the treatment effects of L1 and Desferal on change in T2* MRI in patients without cardiac symptoms. The study provides important evidence to beneficial effect of L1 in improving myocardial iron. The T2* findings are not correlated to change in cardiac function.
15. Giardina PJ, Grady RW. Chelation therapy in beta-thalassemia: an optimistic update. Semin Hematol 2001; 38:360-366.
16. Daar S, Pathare AV. Combined therapy with desferrioxamine and deferiprone in beta thalassemia major patients with transfusional iron overload. Ann Hematol 2006; 85:315-319. A prospective study assessing effect of combined treatment with L1 and Desferal on cardiac function and ferritin levels. Results of 55 complaint patients are shown.
17. Kattamis A, Ladis V, Berdousi H, et al. Iron chelation treatment with combined therapy with deferiprone and desferrioxamine: a 12-month trial. Blood Cells Mol Dis 2006; 36:21-25. The beneficial effect of combined treatment with L1 and Desferal on cardiac function (by echocardiogram and MRI) was studied in 42 patients over a 1-year period.
18. Mourad FH, Hoffbrand AV, Sheikh-Taha M, et al. Comparison between desferrioxamine and combined therapy with desferrioxamine and deferiprone in iron overloaded thalassaemia patients. Br J Haematol 2003; 121:187-189.
19. Origa R, Bina P, Agus A, et al. Combined therapy with deferiprone and desferrioxamine in thalassemia major. Haematologica 2005; 90:1309-1314.
20. Galanello R, Piga A, Alberti D, et al. Safety, tolerability, and pharmacokinetics of ICL670, a new orally active iron-chelating agent in patients with transfusion-dependent iron overload due to beta-thalassemia. J Clin Pharmacol 2003; 43:565-572.
21. Hershko C, Konijn AM, Nick HP, et al. ICL670A: a new synthetic oral chelator: evaluation in hypertransfused rats with selective radioiron probes of hepatocellular and reticuloendothelial iron stores and in iron-loaded rat heart cells in culture. Blood 2001; 97:1115-1122.
22. Cappellini MD, Cohen A, Piga A, et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood 2006; 107:3455-3462. A large, carefully analyzed study that reports the results of a treatment with deferasirox, in three different doses. The choice of treatment dose and the primary endpoint were based on LIC. The study provides detailed data on achieving iron balance with each treatment dose and reports the side-effects seen.
23. Glickstein H, El RB, Shvartsman M, Cabantchik ZI. Intracellular labile iron pools as direct targets of iron chelators: a fluorescence study of chelator action in living cells. Blood 2005; 106:3242-3250. An important analysis of the three iron chleators in current clinical use. The ability of Desferal, L1 and deferasirox to access intracellular iron pools is measured in cell line models. The modes and efficacy of accessing iron pools are shown in models of different iron-loaded cell types. An important groundwork for future preclinical and clinical and studies.
24. Porter JTM, Pennell DJ, Eleftheriou P. Improved myocardial T2* in transfusion dependent anemias receiving ICL670 (Deferasirox). Blood 2005; 106:1003a.
25. Kontoghiorghes GJ. New chelation therapies and emerging chelating drugs for the treatment of iron overload. Expert Opin Emerg Drugs 2006; 11:1-5.
26. Klings ES, Wyszynski DF, Nolan VG, et al. Abnormal pulmonary function in adults with sickle cell anemia. Am J Respir Crit Care Med 2006; in press. The first comprehensive report of pulmonary function tests in 310 adults with SCD, demonstrating abnormal pulmonary function in 90%. Common abnormal findings included restrictive physiology (74%) and decreased diffusion capacity for carbon monoxide.
27. Gladwin M, Sachdev V, Jison M, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med 2004; 350:22-31.
28. Castro O, Hoque M, Brown M. Pulmonary hypertension in sickle cell disease: cardiac catheterization results and survival. Blood 2003; 101:1257-1261.
29. Morris C, Kuypers F, Kato G, et al. Hemolysis-associated pulmonary hypertension in thalassemia. An NY Acad Sci 2005; 1054:481-485. First report of arginine dysregulation and elevated arginase activity in patients with thalassemia as a novel mechanism for the development of pulmonary hypertension.
30. Vichinsky EP. Pulmonary hypertension in sickle cell disease: a time for intervention. N Engl J Med 2004; 350:857-859.
31. Suell MN, Bezold LI, Okcu MF, et al. Increased pulmonary artery pressures among adolescents with sickle cell disease. J Pediatr Hematol Oncol 2005; 27:654-658. Retrospective analysis of 80 adolescents with SCD, identifying abnormal Doppler echocardiography in 26% of patients, although clinical symptoms were rare.
32. Ambrusko SJ, Gunawardena S, Sakara A, et al. Elevation of tricuspid regurgitant jet velocity, a marker for pulmonary hypertension in children with sickle cell disease. Pediatr Blood Cancer 2006; in press. Retrospective analysis of pediatric patients with SCD identifies pulmonary hypertension in 26% of children screened by Doppler echocardiography.
33. Hampl V, Herget J. Role of nitric oxide in the pathogenesis of chronic pulmonary hypertension. Physiol Rev 2000; 80:1337-1372.
34. Morris CR, Kato GJ, Poljakovic M, et al. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension and mortality in sickle cell disease. JAMA 2005; 294:81-90. The authors describe a new disease paradigm involving erythrocyte arginase release during hemolysis, and its subsequent impact on arginine and NO metabolism. This shift toward ornithine-dependent pathways is associated with PHT and increased mortality risk in adults with SCD.
35. Nolan VG, Wyszynski DF, Farrer LA, Steinberg MH. Hemolysis-associated priapism in sickle cell disease. Blood 2005; 106:3264-3267.
36. Kato GJ, Hsieh M, Machado RD, et al. Cerbrovascular disease associated with sickle cell pulmonary hypertension. Am J Hematol 2006; 81:503-510. An interesting case series of sickle cell patients with stroke that demonstrates an association of cerebrovascular disease with increased hemolytic rate and PHT.
37. Azarov I, Huang KT, Basu S, et al. Nitric oxide scavenging by red blood cells as a function of hematocrit and oxygenation. J Biol Chem 2005; 280:39024-39032. An important study that provides further evidence of the critical biological phenomenon that hemoglobin compartmentalization within the erythrocyte reduces reaction rates with NO.
38. Locatelli FCG, Giebel S, Argiolu F, et al. Unrelated donor bone marrow transplantation for class I-II thalassemia pediatric patients. Blood 2005; 106:562a.
39. Reiter C, Wang X, Tanus-Santos J, et al. Cell-free hemoglobin limits nitric oxide bioavailability in sickle cell disease. Nat Med 2002; 8:1383-1389.
40. Morris CR. New strategies for the treatment of pulmonary hypertension in sickle cell disease: the rationale for arginine therapy. Treat Respir Med 2006; 5:31-45.
41. Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993; 329:2002-2012.
42. Gladwin M, Schechter A, Ognibene F, et al. Divergent nitric oxide bioavailability in men and women with sickle cell disease. Circulation 2003; 107:271-278.
43. Morris CR, Kuypers FA, Larkin S, et al. Patterns of arginine and nitric oxide in sickle cell disease patients with vaso-occlusive crisis and acute chest syndrome. J Pediatr Hematol Oncol 2000; 22:515-520.
44. Enwonwu CO. Increased metabolic demand for arginine in sickle cell anaemia. Med Sci Res 1989; 17:997-998.
45. Aslan M, Ryan TM, Adler B, et al. Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease. Proc Natl Acad Sci USA 2001; 98:15215-15220.
46. Kaul DK, Liu XD, Fabry ME, Nagel RL. Impaired nitric oxide-mediated vasodilation in transgenic sickle mouse. Am J Physiol Heart Circ Physiol 2000; 278:H1799-H1806.
47. Eberhardt RT, McMahon L, Duffy SJ, et al. Sickle cell anemia is associated with reduced nitric oxide bioactivity in peripheral conduit and resistance vessels. Am J Hematol 2003; 74:104-111.
48. Belhassen L, Pelle G, Sediame S, et al. Endothelial dysfunction in patients with sickle cell disease is related to selective impairment of shear stress-mediated vasodilation. Blood 2001; 97:1584-1589.
49. Mack AK, Kato GJ. Sickle cell disease and nitric oxide: a paradigm shift? Int J Biochem Cell Biol 2006; 38:1237-1243. Excellent recent review on the role of hemolysis-associated endothelial dysfunction in SCD.
50. Bank N, Aynedjian H, Qiu J, et al. Renal nitric oxide synthases in transgenic sickle cell mice. Kidney Int 1996; 50:184-189.
51. Schnog JB, Teerlink T, Van der Dijs FP, et al. Plasma levels of asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, are elevated in sickle cell disease. Ann Hematol 2005; 84:282-286. First report to describe the potential contribution of elevated asymmetric dimethylarginine (an arginine analogue and inhibitor of all NOSs) in limiting NO oxide availability in SCD.
52. Closs EI, Mann GE. Membrane transport of L-arginine and cationic amino acid analogs. San Diego: Academic Press; 2000.
53. Vallance P. The asymmetrical dimethylarginine/dimethylarginine dimethylaminohydrolase pathway in the regulation of nitric oxide generation. Clin Sci 2001; 100:159-160.
54. Pullamsetti S, Kiss L, Ghofrani HA, et al. Increased levels and reduced catabolism of asymmetric and symmetric dimethylarginines in pulmonary hypertension. FASEB J 2005; 19:1175-1177. An intriguing study demonstrating a role for elevated methylated arginines (asymmetric and symmetric dimethylarginines) in the development of chronic pulmonary artery hypertension in the rat model and in patients suffering from idiopathic pulmonary artery hypertension.
55. Kielstein JT, Bode-Boger SM, Hesse G, et al. Asymmetrical dimethylarginine in idiopathic pulmonary arterial hypertension. Arterioscler Thromb Vasc Biol 2005; 25:1414-1418. An excellent study correlating plasma asymmetrical dimethylarginine levels with cardiovascular indices from right heart catheterization in 57 patients with idiopathic PHT. Elevated asymmetrical dimethylarginine levels are associated with poor pulmonary hemodynamics and are an independent predictor of mortality in this cohort.
56. Sydow K, Munzel T. ADMA and oxidative stress. Atheroscler Suppl 2003; 4:41-51.
57. Berka V, Wu G, Yeh HC, et al. Three different oxygen-induced radical species in endothelial nitric-oxide synthase oxygenase domain under regulation by L-arginine and tetrahydrobiopterin. J Biol Chem 2004; 279:32243-32251.
58. Xia Y, Dawson V, Dawson T, et al. Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury. Proc Natl Acad Sci U S A 1996; 93:6770-6774.
59. Wood KC, Hebbel RP, Lefer DJ, Granger DN. Critical role of endothelial cell-derived nitric oxide synthase in sickle cell disease-induced microvascular dysfunction. Free Radic Biol Med 2006; 40:1443-1453. A significant study that demonstrates a potential role for NOS uncoupling in SCD. In the sickle cell transgenic mouse model, endothelial NOS-dependent superoxide production is reversible by pretreatment with sepiapterin, which generates the endothelial NOS cofactor tetrahydrobiopterin. Endothelial NOS uncoupling and dysfunction may contribute to low nitric oxide bioavailability in SCD.
60. Osei S, Ahima J, Fabry M, et al. Immunohistochemical localization of hempatic nitric oxide synthase in normal and transgenic sickle cell mice: the effect of hypoxia. Blood 1996; 88:3583-3588.
61. Castro O, Gladwin MT. Pulmonary hypertension in sickle cell disease: mechanisms, diagnosis, and management. Hematol Oncol Clin North Am 2005; 19:881-896. A concise and comprehensive overview of hemolysis-associated PHT in SCD.
62. Ataga KI, Sood N, De Gent G, et al. Pulmonary hypertension in sickle cell disease. Am J Med 2004; 117:665-669.
63. Morris CR, Morris SM Jr, Hagar W, et al. Arginine therapy: a new treatment for pulmonary hypertension in sickle cell disease? Am J Respir Crit Care Med 2003; 168:63-69.
64. 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; 90:452-458.
65. Machado RF, Martyr S, Kato GJ, et al. Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension. Br J Haematol 2005; 130:445-453. First study to investigate the safety and efficacy of sildenafil in SCD. Improvement in PHT and exercise tolerance was demonstrated in 12 patients evaluated. The 6-min walk test was shown to be a valid endpoint in this population.
66. Kato GJ, McGowan V, Machado RF, et al. Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood 2006; 107:2279-2285. This provocative analysis demonstrates that lactate dehydrogenase is an excellent biomarker of hemolytic rate, and that lactate dehydrogenase strongly correlates to complications associated with endothelial dysfunction and mortality in adults with SCD.
67. Xu W, Kaneko TF, Zheng S, et al. Increased arginase II and decreased NO synthesis in endothelial cells of patients with pulmonary arterial hypertension. FASEB J 2004; 18:1746-1748.
68. Schnog JB, Jager EH, Van der Dijs FP, et al. Evidence for a metabolic shift of arginine metabolism in sickle cell disease. Ann Hematol 2004; 83:371-375.
69. Bryant R. Asthma in the pediatric sickle cell patient with acute chest syndrome. J Pediatr Health Care 2005; 19:157-162. An interesting retrospective study indicating that children with SCD and asthma have a higher frequency of acute chest syndrome.
70. Knight-Madden JM, Forrester TS, Lewis NA, Greenough A. Asthma in children with sickle cell disease and its association with acute chest syndrome. Thorax 2005; 60:206-210. An important prospective investigation that identified a high prevalence of asthma and bronchial hyper-reactivity in children with SCD compared to ethnically matched controls, and demonstrated that atopic asthma in this cohort was associated with recurrent acute chest syndrome.
71. Boyd JH, Moinuddin A, Strunk RC, DeBaun MR. Asthma and acute chest in sickle-cell disease. Pediatr Pulmonol 2004; 38:229-232.
72. Koumbourlis AC, Zar HJ, Hurlet-Jensen A, Goldberg MR. Prevalence and reversibility of lower airway obstruction in children with sickle cell disease. J Pediatr 2001; 138:188-192.
73. Meurs H, Maarsingh H, Zaagsma J. Arginase and asthma: novel insights into nitric oxide homeostasis and airway hyperresponsiveness. Trends Pharmacol Sci 2003; 24:450-455.
74. Zimmermann N, King NE, Laporte J, et al. Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. J Clin Invest 2003; 111:1863-1874.
75. VanderJagt DJ, Kanellis GJ, Isichei C, et al. Serum and urinary amino acid levels in sickle cell disease. J Trop Pediatr 1997; 43:220-225.
76. Morris CR, Poljakovic M, Lavisha L, et al. Decreased arginine bioavailability and increased arginase activity in asthma. Am J Respir Crit Care Med 2004; 170:148-153.
77. Ricciardolo FL, Zaagsma J, Meurs H. The therapeutic potential of drugs targeting the arginase pathway in asthma. Expert Opin Investig Drugs 2005; 14:1221-1231. An excellent review of the arginase pathway and its role in asthma by experts in the field.
78. DeBoer J, Duyvendak M, Schuurman FE, et al. Roleof L-arginine in the deficiency of nitric oxide and airway hyperreactivity after the allergen-induced early asthmatic reaction in guinea-pigs. Br J Pharmacol 1999; 128:1114-11120.
79. Nordness ME, Lynn J, Zacharisen MC, et al. Asthma is a risk factor for acute chest syndrome and cerebral vascular accidents in children with sickle cell disease. Clin Mol Allergy 2005; 3:2. A well performed retrospective chart review demonstrated that asthma was associated with increased episodes of acute chest syndrome and stroke in children with SCD.
80. Jison ML, Gladwin MT. Hemolytic anemia-associated pulmonary hypertension of sickle cell disease and the nitric oxide/arginine pathway. Am J Respir Crit Care Med 2003; 168:3-4.
81. Rother RP, Bell L, Hillmen P, Gladwin MT. The clinical sequelae of intravascular hemolysis and extracellular plasma hemoglobin: a novel mechanism of human disease. JAMA 2005; 293:1653-1662. Comprehensive review of the implications of hemolysis in disease. The ability of cell-free hemoglobin released from the erythrocyte during hemolysis to rapidly consume NO is discussed, with a focus on its role in the development of PHT and other clinical sequelae.
82. Kato GJ, Martyr S, Blackwelder WC, et al. Levels of soluble endothelium-derived adhesion molecules in patients with sickle cell disease are associated with pulmonary hypertension, organ dysfunction, and mortality. Br J Haematol 2005; 130:943-953. A pivotal investigation that demonstrates a strong association between soluble adhesion molecules, particularly soluble vascular cellular adhesion molecule, and severity of PHT, endothelial dysfunction and mortality in adults with SCD.
83. Nolan VG, Adewoye A, Baldwin C, et al. Sickle cell leg ulcers: associations with haemolysis and SNPs in Klotho, TEK and genes of the TGF-beta/BMP pathway. Br J Haematol 2006; 133:570-578. An important study demonstrating an association of leg ulcers in SCD with increased hemolytic rate. Associations with single nucleotide polymorphisms in candidate genes were identified and the potential significance of these single nucleotide polymorphisms discussed.
84. Lezcano NE, Odo N, Kutlar A, et al. Regular transfusion lowers plasma free hemoglobin in children with sickle-cell disease at risk for stroke. Stroke 2006; 37:1424-1426. An intriguing study evaluating stored sera from the STOP study demonstrated that regular transfusion, known to lowers stroke risk, is associated with a significant reduction in plasma-free hemoglobin and other markers of hemolysis. A role for plasma-free hemoglobin in promoting stroke is hypothesized.
85. Machado RF, Anthi A, Steinberg MH, et al. High N-terminal pro brain natriuretic peptide levels are associated with pulmonary hypertension and risk of death in sickle cell disease. JAMA 2006; in press. A detailed analysis of the potential of brain natriuretic peptide to function as a biomarker of PHT in SCD. Plasma brain natriuretic peptide level was also found to be an independent predictor of mortality.
86. Bernaudin F, Souillet G, Vannier JP, et al. Bone marrow transplantation (BMT) in 14 children with severe sickle cell disease (SCD): the French experience. GEGMO. Bone Marrow Transplant 1993; 12 (Suppl 1):118-121.
87. Brachet C, Azzi N, Demulder A, et al. Hydroxyurea treatment for sickle cell disease: impact on haematopoietic stem cell transplantation's outcome. Bone Marrow Transplant 2004; 33:799-803.
88. Vermylen C, Cornu G, Ferster A, et al. Haematopoietic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium. Bone Marrow Transplant 1998; 22:1-6.
89. Walters MC, Patience M, Leisenring W, et al. Bone marrow transplantation for sickle cell disease. N Engl J Med 1996; 335:369-376.
90. Walters MC, Storb R, Patience M, et al. Impact of bone marrow transplantation for symptomatic sickle cell disease: an interim report. Multicenter investigation of bone marrow transplantation for sickle cell disease. Blood 2000; 95:1918-1924.
91. Hoppe CC, Walters MC. Bone marrow transplantation in sickle cell anemia. Curr Opin Oncol 2001; 13:85-90.
92. Horan JT, Liesveld JL, Fenton P, et al. Hematopoietic stem cell transplantation for multiply transfused patients with sickle cell disease and thalassemia after low-dose total body irradiation, fludarabine, and rabbit antithymocyte globulin. Bone Marrow Transplant 2005; 35:171-177. This article highlights the problem of maintaining stable engraftment of donor cells after nonmyeloablative transplantation for SCD and thalassemia.
93. Iannone R, Casella JF, Fuchs EJ, et al. Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and beta-thalassemia. Biol Blood Marrow Transplant 2003; 9:519-528.
94. Krishnamurti L, Blazar BR, Wagner JE. Bone marrow transplantation without myeloablation for sickle cell disease. N Engl J Med 2001; 344:68.
95. Schleuning M, Stoetzer O, Waterhouse C, et al. Hematopoietic stem cell transplantation after reduced-intensity conditioning as treatment of sickle cell disease. Exp Hematol 2002; 30:7-10.
96. Shenoy S, Grossman WJ, DiPersio J, et al. A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders. Bone Marrow Transplant 2005; 35:345-352. This article describes results after transplantation with a reduced-intensity regimen in children with nonmalignant conditions. It includes patients who received URD allografts with low rates of acute and chronic GVHD.
97. Van Besien K, Bartholomew A, Stock W, et al. Fludarabine-based conditioning for allogeneic transplantation in adults with sickle cell disease. Bone Marrow Transplant 2000; 26:445-449.
98. Van Besien KSW, Sonali S, Peace D, et al. Allogeneic stem cell transplantation with fludarabine melphalan and Campath conditioning for adults with advanced sickle cell disease. Blood 2002; 100:455b.
99. 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; 25:401-404.
100. Nesci S, Manna M, Lucarelli G, et al. Mixed chimerism after bone marrow transplantation in thalassemia. Ann N Y Acad Sci 1998; 850:495-497.
101. Walters MC, Patience M, Leisenring W, et al. Stable mixed hematopoietic chimerism after bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant 2001; 7:665-673.
102. Bernaudin F, Souillet G, Vannier JP, et al. Report of the French experience concerning 26 children transplanted for severe sickle cell disease. Bone Marrow Transplant 1997; 19 (suppl 2):112-115.
103. Ferster A, Bujan W, Corazza F, et al. Bone marrow transplantation corrects the splenic reticuloendothelial dysfunction in sickle cell anemia. Blood 1993; 81:1102-1105.
104. Hernigou P, Bernaudin F, Reinert P, et al. Bone-marrow transplantation in sickle-cell disease. Effect on osteonecrosis: a case report with a four-year follow-up. J Bone Joint Surg Am 1997; 79:1726-1730.
105. Steen RG, Helton KJ, Horwitz EM, et al. Improved cerebrovascular patency following therapy in patients with sickle cell disease: initial results in 4 patients who received HLA-identical hematopoietic stem cell allografts. Ann Neurol 2001; 49:222-229.
106. Kalinyak KA, Morris C, Ball WS, et al. Bone marrow transplantation in a young child with sickle cell anemia. Am J Hematol 1995; 48:256-261.
107. Walters MC, Sullivan KM, Bernaudin F, et al. Neurologic complications after allogeneic marrow transplantation for sickle cell anemia. Blood 1995; 85:879-884.
108. Woodard P, Helton KJ, Khan RB, et al. Brain parenchymal damage after haematopoietic stem cell transplantation for severe sickle cell disease. Br J Haematol 2005; 129:550-552. Single center study of a small group of SCD patients after BMT in whom some had evolution of old and new brain parenchymal lesions.
109. Gaziev J, Lucarelli G. Stem cell transplantation for thalassaemia. Reprod Biomed Online 2005; 10:111-115. Recent comprehensive review of the Italian experience after HCT for thalassemia major.
110. Storb RF, Lucarelli G, McSweeney PA, Childs RW. Hematopoietic cell transplantation for benign hematological disorders and solid tumors. Hematology (Am Soc Hematol Educ Program) 2003; 372-397.
111. Lucarelli G, Galimberti M, Polchi P, et al. Bone marrow transplantation in patients with thalassemia. N Engl J Med 1990; 322:417-421.
112. Sodani P, Gaziev D, Polchi P, et al. New approach for bone marrow transplantation in patients with class 3 thalassemia aged younger than 17 years. Blood 2004; 104:1201-1203.
113. 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; 1054:196-205.
114. Rocha V, Wagner JE Jr, Sobocinski KA, et al. Graft-versus-host disease in children who have received a cord-blood or bone marrow transplant from an HLA-identical sibling. Eurocord and International Bone Marrow Transplant Registry Working Committee on Alternative Donor and Stem Cell Sources. N Engl J Med 2000; 342:1846-1854.
115. Locatelli F, Rocha V, Reed W, et al. Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease. Blood 2003; 101:2137-2143.
116. Walters MC, Quirolo L, Trachtenberg ET, et al. Sibling donor cord blood transplantation for thalassemia major: experience of the sibling donor cord blood program. Ann N Y Acad Sci 2005; 1054:206-213.
117. Adamkiewicz TV, Mehta PS, Boyer MW, et al. Transplantation of unrelated placental blood cells in children with high-risk sickle cell disease. Bone Marrow Transplant 2004; 34:405-411.
118. La Nasa G, Caocci G, Argiolu F, et al. Unrelated donor stem cell transplantation in adult patients with thalassemia. Bone Marrow Transplant 2005; 36:971-975. Update of HLA-identical BMT for thalassemia major in patients older than 17 years of age in which a significant transplant-related mortality was observed even with improvement in supportive care.
119. La Nasa G, Giardini C, Argiolu F, et al. Unrelated donor bone marrow transplantation for thalassemia: the effect of extended haplotypes. Blood 2002; 99:4350-4356.
120. 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; 107:2984-2992. Further refinement of donor selection and HLA mismatching with regard to graft rejection, in this report involving a class II HLA locus, DPB1. In assessing risk factors for graft rejection after HCT for chronic myeloid leukemia, disparities in HLA class I loci were associated with graft rejection.
121. Jaing TH, Hung IJ, Yang CP, et al. Rapid and complete donor chimerism after unrelated mismatched cord blood transplantation in 5 children with beta-thalassemia major. Biol Blood Marrow Transplant 2005; 11:349-353. Single center trial that reported successful outcome after unrelated donor UCB transplantation and suggests UCB might be a suitable stem cell source in thalassemia major.