Supportive care in myelodysplastic syndromes: Hemopoietic cytokine and iron chelation therapy

Myelodysplastic Syndromes: Clinical and Biological Advances

Volumn , Issue , 2005, Pages 209-242

  Jason, Gotlib ^a   Peter, L Greenberg ^a  

^a STANFORD CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84928644596     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1017/CBO9780511545269.009     Document Type: Chapter

References (135)

1. Greenberg, P. L. (1996). Biologic and clinical implications of marrowculture studies in the myelodysplastic syndromes. Semin. Hematol., 33, 163–75
2. Greenberg, P. L. andMara, B. (1979). The preleukemic syndrome: correlation of in vitro parameters of granulopoiesis with clinical features. Am. J. Med., 66, 951–8
3. Chui, D. H. and Clarke, B. J. (1982). Abnormal erythroid progenitor cells in human preleukemia. Blood, 60, 362–7
4. Juvonen, E., Partanen, S., Knuutila, S., and Ruute, T. (1986).Megakaryocyte colony formationbybonemarrowprogenitors inmyelodysplastic syndromes. Br. J.Haematol., 63, 331–4
5. Nagler, A., Ginzton, N., Negrin, R. S. et al.(1990). In vitro differentiative and proliferative effects of human recombinant colony-stimulating factors on marrow hemopoiesis in myelodysplastic syndromes. Leukemia, 4, 193–202
6. Schipperus, M. R., Sonneveld, P., Lindemans, J. et al.(1990). The combined effects of IL-3, GM-CSF, and G-CSF on the in vitro growth of myelodysplastic myeloid progenitor cells. Leuk. Res., 14, 1019–25
7. Greenberg, P. L., Mackichan, M. L., and Negrin, R. (1990). Production of granulocyte colony-stimulating factor by normal andmyelodysplastic syndrome peripheral blood cells. Blood, 76(suppl. 1), 146a (abstract)
8. Nagler, A., Binet, C., Mackichan, M. L. et al.(1990). Impact of marrow cytogenetics and morphology on in vitro hemopoiesis in the myelodysplastic syndromes: comparison between recombinant human granulocyte colony-stimulating factor and granulocyte-monocyte colony-stimulating factor. Blood, 76, 1299–307
9. Merchav, S., Nielsen, O. J., Rosenbaum, H. et al.(1990). In vitro studies of erythropoietin-dependent regulation of erythropoiesis in myelodysplastic syndromes. Leukemia, 4, 771–4
10. Greenberg, P. L., Negrin, R. S., and Ginzton, N. (1991). G-CSF synergizes with erythropoietin for enhancing erythroid colony-formation in myelodysplastic syndromes. Blood, 78(suppl. 1), 38a (abstract)
11. Sawada, K., Sato, N., Tarumi, T. et al.(1993). Proliferation and differentiation of myelodysplasticCD34+cells in serum-free medium: response to individual colonystimulating factors. Br. J. Haematol., 83, 349–58
12. Budel, L. M., Dong, F., Lowenberg, B., andTouw, I. P. (1995).Hematopoietic growth factor receptors: structure variations and alternatives of receptor complex formation in normal hematopoiesis and in hematopoietic disorders. Leukemia, 9, 553–61
13. Hoefsloot, L. H., vanAmelsvoort, M.P., Broeders, L. C. et al.(1997). Erythropoietininduced activation of STAT5 is impaired in the myelodysplastic syndrome. Blood, 89, 1690–700
14. NCCN Myelodysplastic Syndromes Panel (2003). Myelodysplastic syndromes – clinical practice guidelines in oncology. J.N.C.C.N., 1, 456–71
15. Fontenay-Roupie, M., Bouscary, D., Guesnu, M. et al.(1999). Ineffective erythr opoiesis inmyelodysplastic syndromes: correlation with Fas expression but not with lack of erythropoietin receptor signal transduction. Br. J. Haematol., 106, 464–73
16. Claessens, Y. E., Bouscary, D., Dupont, J. M. et al.(2002). In vitro proliferation and differentiation of erythroid progenitors from patients with myelodysplastic syndromes: evidence for Fas-dependent apoptosis. Blood, 99, 1594–601
17. Rigolin, G. M., Della Porta, M., Bigoni, R. et al. (2002). rHuEPO administration in patients with low-risk myelodysplastic syndromes: evaluation of erythroid precursors’ response by fluorescence in situ hybridization onMay-Grunwald-Giemsastained bone marrow samples. Br. J. Haematol., 119, 652–9
18. Schmidt-Mende, J., Tehranchi, R., Forsblom, A. M. et al.(2001). Granulocyte colony-stimulating factor inhibits Fas-triggered apoptosis in bone marrow cells isolated from patients with refractory anemia with ringed sideroblasts. Leukemia,15, 742–51
19. Tehranchi, R., Fadeel, B., Forsblom, A. M. et al. (2003). Granulocyte colonystimulating factor inhibits spontaneous cytochrome c release and mitochondriadependent apoptosis of myelodysplastic syndrome hematopoietic progenitors
20. Adamson, J. W., Schuster, M., Allen, S., and Haley, N. R. (1992). Effectiveness of recombinant human erythropoietin therapy in myelodysplastic syndromes. Acta Haematol., 87(suppl. 1), 20–4
21. Aloe Spiriti, M. A., Petti, M. C., Latagliata, R. et al.(1993). Is recombinant human erythropoietin treatment in myelodysplastic syndromes worthwhile? Leuk. Lymphoma, 9, 79–83
22. Stenke, L., Wallvik, J., Celsing, F., and Hast, R. (1993). Prediction of response to treatment with human recombinant erythropoietin inmyelodysplastic syndromes. Leukemia, 7, 1324–7
23. Stone, R. M., Bernstein, S. H., Demetri, G. et al.(1994).Treatmentwith recombinant human erythropoietin in patients with myelodysplastic syndromes. Leuk. Res., 18, 769–76
24. Rose, E. H., Abels, R. I., Nelson, R. A., McCullough, O. M., and Lessin, L. (1995). The use of r-HuEPO in the treatment of anaemia related tomyelodysplasia (MDS). Br. J. Haematol., 89, 831–7
25. Stasi, R., Brunetti, M., Bussa, S. et al.(1997). Response to recombinant human erythropoietin in patients with myelodysplastic syndromes. Clin. Cancer Res., 3, 733–9
26. ItalianCooperative StudyGroup for rHuEpo inMyelodysplastic Syndromes (1998). A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes. Br. J. Haematol., 103, 1070–4
27. Terpos, E., Mougiou, A., Kouraklis, A. et al.(2002). Prolonged administration of erythropoietin increases erythroid response rate in myelodysplastic syndromes: a phase II trial in 281 patients. Br. J. Haematol., 118, 174–80
28. Wallvik, J., Stenke, L., Bernell, P. et al.(2002). Serum erythropoietin (EPO) levels correlate with survival and independently predict response to EPO treatment in patients with myelodysplastic syndromes. Eur. J. Haematol., 68
29. Rodriguez, J. N., Dieguez, J. C., Muniz, R. et al. (1994). [Human recombinant erythropoietin in the treatment of myelodysplastic syndromes anemia. Meta-analytic study.] Sangre (Barc.), 39, 435–9 (in Spanish)
30. Hellstrom-Lindberg, E. (1995). Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies. Br. J. Haematol., 89, 67–71
31. Hast, R., Wallvik, J., Folin Abernell, P., and Stenke, L. (2001). Long-termfollow-up of 18 patients withmyelodyplastic syndromes responding to recombinant erythropoietin treatment. Leuk. Res., 25, 13–18
32. Musto, P., Falcone, A., Sanpaolo, G. et al.(2003). Efficacy of a single, weekly dose of recombinant erythropoietin in myelodysplastic syndromes. Br. J. Haematol., 122, 267–71
33. Garypidou, V., Verrou, E., Vakalopoulou, S. et al.(2003). Efficacy of a single, weekly dose of recombinant erythropoietin inmyelodysplastic syndromes. Br. J.Haematol., 123, 958
34. Negrin, R. S., Haeuber, D. H., Nagler, A. et al. (1989). Treatment ofmyelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor. Ann. Intern. Med., 110, 976–84
35. Negrin, R. S., Haeuber, D. H., Nagler, A. et al.(1990). Maintenance treatment of patients with myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor. Blood, 76, 36–43
36. Greenberg, P., Taylor, K., Larson, R. et al.(1993). Phase III randomizedmulticenter trial of recombinant human G-CSF in MDS. Blood, 82(suppl. 1), 196a (abstract)
37. Greenberg, P. L., Negrin, R. S., and Ginzton, N. (1992). In vitro–in vivo correlations of erythroid responses to G-CSF plus erythropoietin inmyelodysplastic syndromes. Exp. Hematol., 20, 733 (abstract)
38. Negrin, R. S., Stein, R., Doherty, K. et al.(1993). Treatment of the anemias of MDS using recombinant human granulocyte colony-stimulating factor in combination with erythropoietin. Blood, 82, 737–43
39. Hellstrom-Lindberg, E., Birgegard, G., Carlsson, M. et al. (1993). A combination of granulocyte colony-stimulating factor and erythropoietin may synergistically improve the anaemia in patientswithmyelodysplastic syndromes. Leuk. Lymphoma, 11, 221–8
40. Negrin, R. S., Stein, R., Doherty, K. et al.(1996).Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colonystimulating factor and erythropoietin: evidence for in vivo synergy. Blood, 87, 4076–81
41. Hellstrom-Lindberg, E., Negrin, R., Stein, R. et al. (1997). Erythroid response to treatmentwithG-CSFplus erythropoietin for theanaemiaof patientswithmyelodysplastic syndromes: proposal for a predictive model. Br. J. Haematol., 99, 344–51
42. Hellstrom-Lindberg, E., Ahlgren, T., Beguin, Y. et al. (1998). Treatment of anemia inmyelodysplastic syndromes with granulocyte colony-stimulating factor plus erythropoietin; results from a randomized phase II study and long-term follow-up of 71 patients. Blood, 92, 68–75
43. Hellstrom-Lindberg, E., Gulbrandsen, N., Lindberg, G. et al.(2003). A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin+ granulocyte colony-stimulating factor: significant effects on quality of life. Br. J. Haematol., 120, 1037–46
44. Remacha, A. F., Arrizabalaga, B., Villegas, A. et al.(1999). Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. Haematologica, 84, 1058–64
45. Mantovani, L., Lentini, G., Hentschel, B. et al.(2000). Treatment of anaemia in myelodysplastic syndromes with prolonged administration of recombinant human granulocyte colony-stimulating factor and erythropoietin. Br. J. aematol., 109, 367–75
46. Casadevall, N., Durieux, P., Dubois, S. et al.(2004).Health, economic, and qualityof- life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment ofmyelodysplastic syndromes: a randomized, controlled trial. Blood, 104, 321–7
47. Jadersten, M., Montgomery, S. M., Astermark, J. et al.(2003). Treatment of anemia in myelodysplastic syndromes with granulocyte colony-stimulating factor and erythropoietin: response and impact on survival in a long-term follow-up of 129 patients. Blood, 102(suppl. 1), 184a–5a (abstract)
48. Greenberg, P., Cox, C., Le Beau, M. M. et al.(1997). International scoring system (IPSS) for evaluating prognosis in myelodysplastic syndrome. Blood, 89, 2079–88
49. Vadhan-Raj, S., Keating, M., LeMaistre, A. et al.(1987). Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. N. Engl. J. Med., 317, 1545–52
50. Antin, J. H., Weinberg, D. S., and Rosenthal, D. S. (1990).Variable effect of recombinant human granulocyte-macrophage colony-stimulating factor on bone marrow fibrosis in patients with myelodysplasia. Exp. Hematol., 18, 266–70
51. Ganser, A., Volkers, B., Greher, J. et al.(1989). Recombinant human-granulocytemacrophage colony-stimulating factor in patients withmyelodysplastic syndromes – a phase I/II trial. Blood, 73, 31–7
52. Hermann, F., Lindemann, A., Klein, H. et al.(1989). Effect of recombinant human granulocyte-macrophage colony-stimulating factor in patients withmyelodysplastic syndrome with excess blasts. Leukemia, 3, 335–8
53. Hoelzer, D., Ganser, A., Greher, J., Volkers, B., and Walther, F. (1988). Phase I/II studywithGM-CSFin patientswithmyelodysplastic syndromes. Behring Inst.Mitt., 83, 134–8
54. Thompson, J. A., Douglas, J. L., Kidd, P. et al.(1989). Subcutaneous granulocyte macrophage colony-stimulating factor in patients with myelodysplastic syndrome: toxicity, pharmacokinetics, and hematological effects. J. Clin. Oncol., 7, 629–37
55. Estey, E. H., Kurzrock, R., Talpaz, M. et al.(1991). Effects of low doses of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with myelodysplastic syndromes. Br. J. Haematol., 77, 291–5
56. Rosenfeld, C. S., Sulecki, M., Evans, C., and Shadduck, R. K. (1991). Comparison of intravenous versus subcutaneous recombinant human granulocyte-macrophage colony-stimulating factor in patients with primary myelodysplasia. Exp. Hematol., 19, 273–7
57. Gradishar, W. J., Le Beau, M. M., O’Laughlin, R., Vardiman, J. W., and Larson, R. A. (1992). Clinical and cytogenetic responses to granulocyte-macrophage colony-stimulating factor in therapy-related myelodysplasia. Blood, 80, 2463– 70
58. Takahashi, M., Yoshida, Y., Kaku, K. et al.(1993). Phase II study of recombinant granulocyte-macrophage colony-stimulating factor in myelodysplastic syndrome and aplastic anemia. Acta Haematol., 89, 189–94
59. Rose, C., Wattel, E., Bastion, Y. et al. (1994). Treatmentwith very low-dose GM-CSF in myelodysplastic syndromes with neutropenia. A report on 28 cases. Leukemia, 8, 1458–62
60. Willemze, R., Van Der Lely, N., Zwierzina, H. et al.(1992). A randomized phase-I/II multicenter study of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy for patientswithmyelodysplastic syndromes and a relatively low risk of acute leukemia. Ann. Hematol., 64, 173–80
61. Schuster, M. W., Thompson, J. A., Larson, R. et al.(1995). Randomized phase II study of recombinant granulocyte macrophage-colony stimulating factor (rGMCSF) in patients with neutropenia secondary tomyelodysplastic syndrome (MDS). Blood, 86(suppl. 1), 338a (abstract)
62. Yoshida, Y., Nakahata, T., Shibata, A. et al.(1995). Effects of long-term treatment with recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndrome. Leuk. Lymphoma, 18, 457–
63. Runde, V., Aul, C., Ebert, A., Grabenhorst, U., and Schneider, W. (1995). Sequential administration of recombinant human granulocyte-macrophage colonystimulating factor and human erythropoietin for treatment of myelodysplastic
64. syndromes. Eur. J. Haematol., 54, 39–45
65. Hansen, P. B., Johnsen, H. E., Hippe, E., Hellstrom-Lindberg, E., and Ralfkiaer, E. (1993). Recombinant human granulocyte-macrophage colony-stimulting factor plus recombinant human erythropoietin may improve anemia in selected patients with myelodysplastic syndromes. Am. J. Hematol., 44, 229–36
66. Bernell, P., Stenke, L., Wallvik, J., Hippe, E., and Hast, R. (1996). A sequential erythropoietin and GM-CSF schedule offers clinical benefits in the treatment of anemia in myelodysplastic syndromes. Leuk. Res., 20, 693–9
67. Stasi, R., Pagano, A., Terzoli, E., and Amadori, S. (1999). Recombinant human granulocyte-macrophage colony-stimulating factor plus erythropoietin for the treatment of cytopenias in patients with myelodysplastic syndromes. Br. J. Haematol., 105, 141–8
68. Thompson, J., Gilliland, G., Prchal, J. et al.(1995). The use of GM-CSF+r-HuEPO for the treatment of cytopenias associated with myelodysplastic syndromes. Blood, 86(suppl. 1), 337a (abstract)
69. Economopoulos, T., Mellou, S., Papageorgiou, E. et al.(1999). Treatment of anemia in low risk myelodysplastic syndromes with granulocyte-macrophage colony-stimulating factor plus recombinant human erythropoietin. Leukemia, 13, 1009–12
70. Tefferi, A., Elliott, M. A., Steensma, D. P. et al.(2001). Amifostine alone and in combination with erythropoietin for the treatment of favorable myelodysplastic syndrome. Leuk. Res., 25, 183–5
71. Neumeister, P., Jaeger, G., Eibl, M. et al.(2001). Amifostine in combination with erythropoietin and G-CSF promotes multilineage hematopoiesis in patients with myelodysplastic syndrome. Leuk. Lymphoma, 40, 345–9
72. Tsiara, S. N., Kapsali, H. D., Panteli, K., Christou, L., and Bourantas, K. L. (2001). Preliminary results of amifostine administration in combination with recombinant human erythropoietin in patients with myelodysplastic syndromes. J. Exp. Clin. Cancer Res., 20, 35–8
73. Grossi, A., Musto, P., Santini, V. et al.(2002). Combined therapy with amifostine plus erythropoietin for the treatmentofmyelodysplastic syndromes.Haematologica, 87, 322–3
74. Stasi, R., Brunetti, M., Terzoli, E., and Amadori, S. (2002). Sustained response to recombinant human erythropoietin and intermittent all-trans retinoic acid in patients with myelodysplastic syndromes. Blood, 99, 1578–84
75. Ganser, A., Seipelt, G., Lindemann, A. et al.(1990). Effects of recombinant human interleukin-3 in patients with myelodysplastic syndromes. Blood, 76, 455–62
76. Kurzrock, R., Talpaz, M., Estrov, Z., Rosenblum, M. G., and Gutterman, J.U. (1991). Phase I study of recombinant human interleukin-3 in patients with bone marrow failure. J. Clin. Oncol., 9, 1241–50
77. Nimer, S.D., Paquette, R. L., Ireland, P. et al. (1994).Aphase I/II studyof interleukin- 3 in patients with aplastic anemia and myelodysplasia. Exp. Hematol., 22, 875–80
78. Ganser, A., Ottmann, O. G., Seipelt, G. et al.(1993). Effect of long-term treatment with recombinant human interleukin-3 in patients with myelodysplastic syndromes. Leukemia, 7, 696–701
79. Miller, A. M., Noyes, W. E., Taetle, R., and List, A. F. (1999). Limited erythropoietic response to combined treatment with recombinant human interleukin 3 and erythropoietin in myelodysplastic syndrome. Leuk. Res., 23, 77–83
80. Gordon, M. S., Nemunaitis, J., Hoffman, R. et al.(1995). A phase I trial of recombinant human interleukin-6 in patients withmyelodysplastic syndromes and thrombocytopenia. Blood, 85, 3066–76
81. Kurzrock, R., Cortes, J., Thomas, D. A. et al.(2001) Pilot study of low-dose interleukin-II in patients with bone marrow failure. J. Clin. Oncol., 19, 4165–72
82. Lok, S., Kaushansky, K., Holly, R.D. et al. (1994). Cloning and expression of murine thrombopoietin cDNA and stimulation of platelet production in vivo. Nature, 369, 565–8
83. De Sauvage, F. J., Hass, P. E., Spencer, S. D. et al.(1994). Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-mpl ligand. Nature, 369, 533–8
84. Kaushansky, K., Lok, S., Holly, R.D. et al.(1994). Promotion of megakaryocyte progenitor expansion and differentiation by the c-mpl ligand thrombopoietin. Nature, 369, 568–71
85. Wendling, F., Maraskovsky, E., Debili, N. et al. (1994). cMpl ligand is a humoral regulator of megakaryocytopoieisis. Nature, 369, 571–4
86. Bartley, T. D., Bogenberger, J., Hunt, P. et al.(1994). Identification and cloning of a megakaryocyte and development factor that is a ligand for the cytokine receptor mpl. Cell, 77, 1117–24
87. Debili, N., Wendling, F., Katz, A. et al.(1995). The Mpl-ligand or thrombopoietin of megakaryocyte growth and differentiative factor has both direct proliferative and differentiative activities on human megakaryocyte progenitors. Blood, 86, 2516–25
88. Sitnicka, E., Lin, N., Priestley, G. V. et al.(1996). The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells. Blood, 87, 4998–5005
89. Katayama, N., Itoh, R., Kato, T. et al.(1997). Role for C-MPL and its ligand thrombopoietin in early hematopoiesis. Leuk. Lymphoma, 28, 51–6
90. Molineaux, G., Hartley, C., McElroy, P., McCrea, C., and McNiece, I. K. (1996). Megakaryocyte growth and development factor accelerates platelet recovery in peripheral blood progenitor cell transplant recipients. Blood, 88, 366–76
91. Farese, A. M., Hunt, P., Grab, L. B., and MacVittie, T. J. (1996). Combined administration of recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor enhances multilineage hematopoietic reconstitution in non-human primates after radiation-induced marrow aplasia. J. Clin. Invest., 97, 2145–51
92. Basser, R. L., Rasko, J. E., Clarke, K. et al.(1996). Thrombopoietic effects of pegylated recombinant human megakaryocyte growth and development factor (PEGrHuMGDF) in patients with advanced cancer. Lancet, 348, 1279–81
93. Vadhan-Raj, S., Murray, L. J., Bueso-Ramos, C. et al.(1997). Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer. Ann. Intern. Med., 126, 673–81
94. Basser, R. L., Rasko, J. E., Clarke, K. et al.(1997). Randomized, blinded, placebocontrolled phase I trial of pegylated recombinanthumanmegakaryocyte growthand development factor with filgrastim after dose-intensive chemotherapy in patients with advanced cancer. Blood, 89, 3118–28
95. Fanucchi, M., Glaspy, J., Crawford, J. et al.(1997). Effects of polyethylene glycolconjugated recombinant human megakaryocyte growth and development factor on platelet counts after chemotherapy for lung cancer. N. Engl. J. Med., 336, 404–9
96. Emmons, R. V., Reid, D. M., Cohen, R. L. et al.(1996). Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction. Blood, 87, 4068–71
97. Wang, W., Matsuo, T., Yoshida, S. et al. (2000).Colony-forming unit-megakaryocyte (CFR-meg) numbers and serum thrombopoietin concentrations in thrombocytopenic disorders: an inverse correlation in myelodysplastic syndromes. Leukemia, 14, 1751–6
98. Zwierzina, H., Rollinger-Holzinger, I., Nuessler, V., Herold, M., and Meng, Y. G. (1998). Endogenous serum thrombopoietin concentrations in patients with myelodysplastic syndromes. Leukemia, 12, 59–64
99. Tamura, H., Ogata, K., Luo, S. et al. (1998). Plasma thrombopoietin(TPOlevels)and expression ofTPOreceptor on platelets in patientswithmyelodysplastic syndromes. Br. J. Haematol., 103, 778–84
100. Fontenay-Roupie, M., Dupont, J. M., Picard, F. et al.(1998). Analysis of megakaryocyte growth and development factor (thrombopoietin) effects on blast cell and megakaryocyte growth in myelodysplasia. Leuk. Res., 22, 527–35
101. Luo, S. S., Ogata, K., Yokose, N., Kato, T., and Dan, K. (2000). Effect of thrombopoietin on proliferation of blasts from patients withmyelodysplastic syndromes. Stem Cells, 18, 112–19
102. Adams, J. A., Liu Yin, J. A., Brereton, M. L. et al.(1997). The in vitro effect of pegylated recombinant human megakaryocyte growth and development factor (PEG rHuMGDF) on megakarypoiesis in normal subjects and patients with myelodysplasia and acute myeloid leukemia. Br. J. Haematol., 99, 139–46
103. Liu Yin, J. A., Adams, J. A., Brereton, M. L. et al.(2000).Megakaryopoiesis in vitro in myelodysplastic syndromes and acutemyeloid leukemia: effect of pegylated recombinant human megakaryocyte growth and development factor in combinationwith other growth factors. Br. J. Haematol., 108, 743–6
104. Ferrajoli, A., Talpaz, M., Kurzrock, R. et al. (1998). Thrombopoietin stimulates myelodysplastic syndrome granulocyte-macrophage and erythroid progenitor proliferation. Leuk. Lymphoma, 30, 279–92
105. Komatsu, N., Okamoto, T., Yoshida, T. et al.(2000). Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) increased platelet counts (PLT) in patients (pts) with aplastic anemia (AA) and myelodysplastic syndrome (MDS). Blood, 96, 296a (abstract)
106. Kizaki, M., Yoshitaka, M., and Ikeda, Y. (2003). Long-termadministration of pegylated recombinant human megakaryocyte growth and development factor dramatically improved cytopenias in a patient with myelodysplastic syndrome. Br. J. Haematol., 122, 764–7
107. Olivieri, N. F. (1999). The beta-thalassemias. N. Engl. J. Med., 341, 99–109
108. Hershko, C., Graham, G., Bates, G.W., and Rachmilewitz, E. A. (1978).Non-specific serum iron in thalassemia: an abnormal serum iron fraction of potential toxicity. Br. J. Haematol., 40, 255–63
109. Farquhar, M. J. and Bowen, D. T. (2003). Oxidative stress and the myelodysplastic syndromes. Int. J. Hematol., 77, 342–50
110. Gotlib, J. andGreenberg, P. L. (2002).Myelodysplastic syndromes. In Leukemia, 7th Edn, ed. E. Henderson, T. Lister, M. F. Greaves. New York: Churchill Livingstone, pp. 545–82
111. Olivieri, N. F., Nathan, D. G., MacMillan, J. H. et al.(1994). Survival in medically treated patients with homozygous beta-thalassemia. N. Engl. J. Med., 331, 574–8
112. Brittenham, G. M., Griffith, P. M., Nienhuis, A. W. et al.(1994). Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N. Engl. J. Med., 331, 567–73
113. Olivieri, N. F. and Brittenham, G. M. (1997). Iron-chelating therapy and the treatment of thalassemia. Blood, 89, 739–61
114. Jensen, P. D., Heickendorff, L., Bendix-Hansen, K. et al.(1996). The effect of iron chelation on haemopoiesis in MDS patients with transfusional iron overload. Br. J. Haematol., 94, 288–99
115. Franchini, M., Gandini, G., de Gironcoli, M. et al.(2000). Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload. Blood, 95, 2776–9
116. Franchini, M., Gandini, G., Veneri, D., and Aprili, G. (2004). Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload: an update. Blood, 103, 747–8
117. Hoffbrand, A. V., Cohen, A., and Hershko, C. (2003). Role of deferiprone in chelation therapy for transfusional iron overload. Blood, 102, 17–24
118. Cohen, A. R., Galanello, R., Piga, A., De Sanctis, V., and Tricta, F. (2003). Safety and effectiveness of long-term therapy with the oral iron chelator deferiprone. Blood, 102, 1583–7
119. Olivieri, N. F., Brittenham, G. M., McLaren, C. E. et al.(1998). Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. N. Engl. J. Med., 339, 417–23
120. Hoffbrand, A.V., Al-Refaie, F., Davis, B. et al.(1998). Long-termtrial of deferiprone in 51-transfusion-dependent iron overloaded patients. Blood, 91, 295–300
121. Stella, M., Pinzello, G., andMaggio, A. (1998). Iron chelation with oral deferiprone in patients with thalassemia. N. Engl. J. Med., 339, 1710–11
122. Tondury, P., Zimmermann, A., Nielsen, P., and Hirt, A. (1998). Liver iron and fibrosis during long-termtreatmentwith deferiprone inSwiss thalassaemic patients. Br. J. Haematol., 101, 413–15
123. Berdoukas, V., Bohane, T., Eagle, C. et al.(2000). The Sidney Children’s Hospital experience with the oral iron chelator deferiprone (L1). Transfus. Sci., 23, 239–40
124. Wanless, I. R., Sweeney, G., Dhillon, A. P. et al.(2002). Lack of progressive hepatic fibrosis during long-term therapy with deferiprone in subjects with transfusiondependent beta-thalassemia. Blood, 100, 1566–9
125. Addis, A., Loebstein, R., Koren, G., and Einarson, T. R. (1999).Meta-analytic review of the clinical effectiveness of oral deferiprone (L1). Eur. J. Clin. Pharmacol., 55, 1–6
126. Barman Balfour, J. A. and Foster, R. H. (1999). Deferiprone: a review of its clinical potential in iron overload in beta-thalassaemia major and other transfusiondependent diseases. Drugs, 58, 553–78
127. Kersten, M. J., Lange, R., Smeets, M. E. et al.(1996). Long-term treatment of transfusional iron overload with the oral iron chelator deferiprone (L1): a Dutch multicenter trial. Ann. Hematol., 73, 247–52
128. Pootrakul, P., Sirankapracha, P., Sankote, J. et al.(2003). Clinical trial of deferiprone iron chelation therapy in beta-thalassaemia/haemoglobin E patients in Thailand. Br. J. Haematol., 122, 305–10
129. Nick, H., Acklin, P., Lattmann, R. et al.(2003). Development of tridentate iron chelators: from desferrithiocin to ICL670. Curr. Med. Chem., 10, 1065–76
130. Nisbet-Brown, E., Olivieri, N. F., Giardina, P. J. et al.(2003). Effectiveness and safety of ICL670 in iron-loaded patients with thalassaemia: a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet, 361, 1597–602
131. Piga, A., Galanello, R., Cappellini, M.D. et al.(2002). Phase II study of oral chelator ICL670 in thalassaemia patients with transfusional iron overload: efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) after 6 months of therapy. Blood, 100(suppl. 1), 5a (abstract)
132. Piga, A., Galanello, R., Cappellini, M. D. et al.(2003). Phase II study of ICL670, an oral chelator, in adult thalassaemia patients with transfusional iron overload: efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD) after 18 months of therapy. Blood, 102(suppl. 1), 121a (abstract)
133. Cheson, B.D., Bennett, J. M., Kantarjian, H. et al.(2000). Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood, 96, 3671–4
134. Bowen, D. T. and Hellstrom-Lindberg, E. (2001). Best supportive care for the anaemia ofmyelodysplasia: inclusion of recombinant erythropoietin therapy? Leuk. Res., 25, 19–21
135. Nicolas, G., Bennoun, M., Devaux, I. et al.(2001). Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc. Natl Acad. Sci. U.S.A., 98, 8780–5.