Supportive care, growth factors, and new therapies in myelodysplastic syndromes

Blood Reviews

Volumn 22, Issue 2, 2008, Pages 75-91

  Hellström Lindberg, Eva ^a   Malcovati, Luca ^b  

^a KAROLINSKA INSTITUTE   (Sweden)

^b UNIVERSITY OF PAVIA   (Italy)

Author keywords

Acute myeloid leukemia; Myelodysplasia; Pathogenesis; Treatment

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; ANGIOGENESIS INHIBITOR; ARSENIC TRIOXIDE; AZACITIDINE; BEVACIZUMAB; CYCLOSPORIN A; CYTARABINE; GLUTATHIONE DERIVATIVE; GRANULOCYTE COLONY STIMULATING FACTOR; HEMOGLOBIN; HEMOPOIETIC GROWTH FACTOR; HISTONE DEACETYLASE INHIBITOR; IMATINIB; IMMUNOSUPPRESSIVE AGENT; IRON; LENALIDOMIDE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; PRINOMASTAT; PROTEIN FARNESYLTRANSFERASE INHIBITOR; PROTEIN TYROSINE KINASE INHIBITOR; RECOMBINANT ERYTHROPOIETIN; SUNITINIB; THALIDOMIDE; THYMOCYTE ANTIBODY; TLK 199; TUMOR NECROSIS FACTOR ALPHA ANTIBODY; UNCLASSIFIED DRUG; VALPROIC ACID; VATALANIB;

ANEMIA; ANGIOGENESIS; APOPTOSIS; ARTICLE; CELL CLONING; CELL MATURATION; CELL PROLIFERATION; CELL SURVIVAL; CHROMOSOME ANALYSIS; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; DISEASE CLASSIFICATION; DISEASE SEVERITY; DOSE RESPONSE; DRUG HALF LIFE; DRUG MECHANISM; DRUG WITHDRAWAL; EPIGENETICS; ERYTHROCYTE; ERYTHROID CELL; GENE DELETION; HEMATOPOIESIS; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMAN; IRON CHELATION; LEUKEMIA; LONG TERM CARE; MORTALITY; MYELODYSPLASTIC SYNDROME; NEUTROPENIA; PATIENT CARE; PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL; REMISSION; RISK ASSESSMENT; THROMBOCYTOPENIA; TREATMENT RESPONSE;

DISEASE PROGRESSION; EPIGENESIS, GENETIC; ERYTHROPOIETIN; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS; MYELODYSPLASTIC SYNDROMES; NEUTROPENIA; REMISSION INDUCTION;

EID: 39649114580     PISSN: 0268960X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.blre.2007.10.003     Document Type: Article

References (137)

1. Cazzola M., and Malcovati L. Myelodysplastic syndromes-coping with ineffective hematopoiesis. N Engl J Med 352 (2005) 536-538
2. Bennett J.M., Catovsky D., Daniel M.T., et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 51 (1982) 189-199
3. Vardiman J.W., Harris N.L., and Brunning R.D. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 100 (2002) 2292-2302
4. Germing U., Gattermann N., Strupp C., Aivado M., and Aul C. Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res 24 (2000) 983-992
5. Malcovati L., Della Porta M., Pascutto C., et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria. A basis for clinical decision-making. J Clin Oncol 23 (2005) 7594-7603
6. Howe R.B., Porwit-MacDonald A., Wanat R., Tehranchi R., and Hellstrom-Lindberg E. The WHO classification of MDS does make a difference. Blood 103 (2004) 3265-3270
7. Verburgh E., Achten R., Maes B., et al. Additional prognostic value of bone marrow histology in patients subclassified according to the International Prognostic Scoring System for myelodysplastic syndromes. J Clin Oncol 21 (2003) 273-282
8. Greenberg P., Cox C., LeBeau M.M., et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89 (1997) 2079-2088
9. de Witte T., Suciu S., Verhoef G., et al. Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDSs) and acute myeloid leukemia following MDS. Blood 98 (2001) 2326-2331
10. Malcovati L., Germing U., Kuendgen A., et al. A WHO Classification-Based Prognostic Scoring System (WPSS) for Predicting Survival in Myelodysplastic Syndromes. Blood 106 (2005) 788
11. Bowen D.T., and Hellstrom-Lindberg E. Treatment of Anemia in Myelodysplastic Syndromes. In: Bennet J.M. (Ed). The Myelodysplastic Syndromes in Pathobiology and Clinical Management (2002), Marcel Dekker Inc., New York 345-372
12. Maschek H., Kaloutsi V., Rodriguez-Kaiser M., et al. Hypoplastic myelodysplastic syndrome: incidence, morphology, cytogenetics, and prognosis. Ann Hematol 66 (1993) 117-122
13. Vander Heiden M.G., and Thompson C.B. Bcl-2 proteins: regulators of apoptosis or of mitochondrial homeostasis?. Nat Cell Biol 1 (1999) E209-E216
14. Wajant H. The Fas signaling pathway: more than a paradigm. Science 296 (2002) 1635-1636
15. De Maria R., Testa U., Luchetti L., et al. Apoptotic role of Fas/Fas ligand system in the regulation of erythropoiesis. Blood 93 (1999) 796-803
16. Claessens Y.E., Bouscary D., Dupont J.M., et al. In vitro proliferation and differentiation of erythroid progenitors from patients with myelodysplastic syndromes: evidence for Fas-dependent apoptosis. Blood 99 (2002) 1594-1601
17. Claessens Y.E., Park S., Dubart-Kupperschmitt A., et al. Rescue of early-stage myelodysplastic syndrome-deriving erythroid precursors by the ectopic expression of a dominant-negative form of FADD. Blood 105 (2005) 4035-4042
18. Tehranchi R., Fadeel B., Forsblom A.M., et al. Granulocyte colony-stimulating factor inhibits spontaneous cytochrome c release and mitochondria-dependent apoptosis of myelodysplastic syndrome hematopoietic progenitors. Blood 101 (2003) 1080-1086
19. Tehranchi R., Invernizzi R., Grandien A., et al. Aberrant mitochondrial iron distribution and maturation arrest characterize early erythroid precursors in low-risk myelodysplastic syndromes. Blood 106 (2005) 247-253
20. Bouscary D., De Vos J., Guesnu M., et al. Fas/Apo-1 (CD95) expression and apoptosis in patients with myelodysplastic syndromes. Leukemia 11 (1997) 839-845
21. Verhoef G.E., De Schouwer P., Ceuppens J.L., Van Damme J., Goossens W., and Boogaerts M.A. Measurement of serum cytokine levels in patients with myelodysplastic syndromes. Leukemia 6 (1992) 1268-1272
22. Otsuki T., Nagakura S., Wang J., Bloom M., Grompe M., and Liu J.M. Tumor necrosis factor-alpha and CD95 ligation suppress erythropoiesis in Fanconi anemia C gene knockout mice. J Cell Physiol 179 (1999) 79-86
23. Hellstrom-Lindberg E., Schmidt-Mende J., Forsblom A.M., Christensson B., Fadeel B., and Zhivotovsky B. Apoptosis in refractory anaemia with ringed sideroblasts is initiated at the stem cell level and associated with increased activation of caspases. Br J Haematol 112 (2001) 714-726
24. May A., de Souza P., Barnes K., Kaaba S., and Jacobs A. Erythroblast iron metabolism in sideroblastic marrows. Br J Haematol 52 (1982) 611-621
25. Sakura T., Murakami H., Saitoh T., Naruse T., and Tsuchiya J. Ultrastructural abnormalities of bone marrow erythroblasts in refractory anemia. Ultrastruct Pathol 22 (1998) 173-180
26. van de Loosdrecht A.A., Brada S.J., Blom N.R., et al. Mitochondrial disruption and limited apoptosis of erythroblasts are associated with high risk myelodysplasia. An ultrastructural analysis. Leuk Res 25 (2001) 385-393
27. Gattermann N., Wulfert M., Junge B., Germing U., Haas R., and Hofhaus G. Ineffective hematopoiesis linked with a mitochondrial tRNA mutation (G3242A) in a patient with myelodysplastic syndrome. Blood 103 (2004) 1499-1502
28. Shin M.G., Kajigaya S., Levin B.C., and Young N.S. Mitochondrial DNA mutations in patients with myelodysplastic syndromes. Blood 101 (2003) 3118-3125
29. Cazzola M., Invernizzi R., Bergamaschi G., et al. Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia. Blood 101 (2003) 1996-2000
30. Della Porta M.G., Malcovati L., Galli{dotless}̀ A., et al. Mitochondrial Ferritin Expression and Clonality of Hematopoiesis in Patients with Refractory Anemia with Ringed Sideroblasts. Blood 106 (2005) 3444
31. Parker J.E., and Mufti G.J. The myelodysplastic syndromes: a matter of life or death. Acta Haematol 111 (2004) 78-99
32. Barrett J., Saunthararajah Y., and Molldrem J. Myelodysplastic syndrome and aplastic anemia: distinct entities or diseases linked by a common pathophysiology?. Semin Hematol 37 (2000) 15-29
33. Saunthararajah Y., Nakamura R., Nam J.M., et al. HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome. Blood 100 (2002) 1570-1574
34. Molldrem J.J., Caples M., Mavroudis D., Plante M., Young N.S., and Barrett A.J. Antithymocyte globulin for patients with myelodysplastic syndrome. Br J Haematol 99 (1997) 699-705
35. Aguayo A. The role of angiogenesis in the biology and therapy of myelodysplastic syndromes. Curr Hematol Rep 3 (2004) 184-191
36. Panoskaltsis N. Dendritic cells in MDS and AML-cause, effect or solution to the immune pathogenesis of disease?. Leukemia 19 (2005) 354-357
37. Delforge M., Raets V., Van Duppen V., Vandenberghe P., and Boogaerts M. CD34+ marrow progenitors from MDS patients with high levels of intramedullary apoptosis have reduced expression of alpha4beta1 and alpha5beta1 integrins. Leukemia 19 (2005) 57-63
38. Kiladjian J.J., Bourgeois E., Lobe I., et al. Cytolytic function and survival of natural killer cells are severely altered in myelodysplastic syndromes. Leukemia 20 (2006) 463-470
39. Lai J.L., Preudhomme C., Zandecki M., et al. Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoiesis and a high incidence of P53 mutations. Leukemia 9 (1995) 370-381
40. Christiansen D.H., Andersen M.K., and Pedersen-Bjergaard J. Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol 19 (2001) 1405-1413
41. Parker J.E., Fishlock K.L., Mijovic A., Czepulkowski B., Pagliuca A., and Mufti A. 'Low-risk' myelodysplastic syndrome is associated with excessive apoptosis and an increased ratio of pro- versus anti-apoptotic bcl-2-related proteins. Br J Haematol 103 (1998) 1075-1082
42. Parker J.E., Mufti G.J., Rasool F., Mijovic A., Devereux S., and Pagliuca A. The role of apoptosis, proliferation, and the Bcl-2-related proteins in the myelodysplastic syndromes and acute myeloid leukemia secondary to MDS. Blood 96 (2000) 3932-3938
43. Rajapaksa R., Ginzton N., Rott L.S., and Greenberg P.L. Altered oncoprotein expression and apoptosis in myelodysplastic syndrome marrow cells. Blood 88 (1996) 4275-4287
44. Reuter C.W., Morgan M.A., and Bergmann L. Targeting the Ras signaling pathway: a rational, mechanism-based treatment for hematologic malignancies?. Blood 96 (2000) 1655-1669
45. Shih L.Y., Huang C.F., Wang P.N., et al. Acquisition of FLT3 or N-ras mutations is frequently associated with progression of myelodysplastic syndrome to acute myeloid leukemia. Leukemia 18 (2004) 466-475
46. Gallagher A., Darley R., and Padua R.A. RAS and the myelodysplastic syndromes. Pathol Biol (Paris) 45 (1997) 561-568
47. List A.F., Vardiman J., Issa J.P., and DeWitte T.M. Myelodysplastic syndromes. Hematology (Am Soc Hematol Educ Program) (2004) 297-317
48. Kamb A., Gruis N.A., Weaver-Feldhaus J., et al. A cell cycle regulator potentially involved in genesis of many tumor types. Science 264 (1994) 436-440
49. Hirama T., and Koeffler H.P. Role of the cyclin-dependent kinase inhibitors in the development of cancer. Blood 86 (1995) 841-854
50. Uchida T., Kinoshita T., Nagai H., et al. Hypermethylation of the p15INK4B gene in myelodysplastic syndromes. Blood 90 (1997) 1403-1409
51. Quesnel B., Guillerm G., Vereecque R., et al. Methylation of the p15(INK4b) gene in myelodysplastic syndromes is frequent and acquired during disease progression. Blood 91 (1998) 2985-2990
52. Daskalakis M., Nguyen T.T., Nguyen C., et al. Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2'-deoxycytidine (decitabine) treatment. Blood 100 (2002) 2957-2964
53. Batova A., Shao L.E., Diccianni M.B., et al. The histone deacetylase inhibitor AN-9 has selective toxicity to acute leukemia and drug-resistant primary leukemia and cancer cell lines. Blood 100 (2002) 3319-3324
54. Kuendgen A., Strupp C., Aivado M., et al. Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans retinoic acid. Blood 104 (2004) 1266-1269
55. Izaks G.J., Westendorp R.G., and Knook D.L. The definition of anemia in older persons. Jama 281 (1999) 1714-1717
56. Penninx B.W., Guralnik J.M., Onder G., Ferrucci L., Wallace R.B., and Pahor M. Anemia and decline in physical performance among older persons. Am J Med 115 (2003) 104-110
57. Wu W.C., Rathore S.S., Wang Y., Radford M.J., and Krumholz H.M. Blood transfusion in elderly patients with acute myocardial infarction. N Engl J Med 345 (2001) 1230-1236
58. Hellstrom-Lindberg E., Gulbrandsen N., Lindberg G., et al. 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 (2003) 1037-1046
59. Jansen A.J., Essink-Bot M.L., Beckers E.A., Hop W.C., Schipperus M.R., and Van Rhenen D.J. Quality of life measurement in patients with transfusion-dependent myelodysplastic syndromes. Br J Haematol 121 (2003) 270-274
60. Alessandrino E.P., Amadori S., Barosi G., et al. Evidence- and consensus-based practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology. Haematologica 87 (2002) 1286-1306
61. Bowen D., Culligan D., Jowitt S., et al. Guidelines for the diagnosis and therapy of adult myelodysplastic syndromes. Br J Haematol 120 (2003) 187-200
62. Cutler C.S., Lee S.J., Greenberg P., et al. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood 104 (2004) 579-585
63. Angelucci E., Muretto P., Nicolucci A., et al. Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation. Blood 100 (2002) 17-21
64. Franchini M., Gandini G., de Gironcoli M., Vassanelli A., Borgna-Pignatti C., and Aprili G. Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload. Blood 95 (2000) 2776-2779
65. Cappellini M.D., 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 107 (2006) 3455-3462
66. Cantor A.B., and Orkin S.H. Transcriptional regulation of erythropoiesis: an affair involving multiple partners. Oncogene 21 (2002) 3368-3376
67. Testa U. Apoptotic mechanisms in the control of erythropoiesis. Leukemia 18 (2004) 1176-1199
68. Aul C., Arning M., Runde V., and Schneider W. Serum erythropoietin concentrations in patients with myelodysplastic syndromes. Leuk Res 15 (1991) 571-575
69. Hellstrom E., Birgegard G., Lockner D., Helmers C., Ost A., and Wide L. Treatment of myelodysplastic syndromes with recombinant human erythropoietin. Eur J Haematol 47 (1991) 355-360
70. Bowen D., Culligan D., and Jacobs A. The treatment of anaemia in the myelodysplastic syndromes with recombinant human erythropoietin. Br J Haematol 77 (1991) 419-423
71. Aloe Spiriti M.A., Petti M.C., Latagliata R., et al. Recombinant human erythropoietin in the treatment of myelodysplastic syndromes. An interim report. Haematologica 78 (1993) 123-126
72. Hellstrom-Lindberg E. Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies. Br J Haematol 89 (1995) 67-71
73. Stein R.S., Abels R.I., and Krantz S.B. Pharmacologic doses of recombinant human erythropoietin in the treatment of myelodysplastic syndromes. Blood 78 (1991) 1658-1663
74. A randomized double-blind placebo-controlled study with subcutaneous recombinant human erythropoietin in patients with low-risk myelodysplastic syndromes. Italian Cooperative Study Group for rHuEpo in Myelodysplastic Syndromes. Br J Haematol 1998;103:1070-1074.
75. Hellstrom-Lindberg E., Negrin R., Stein R., et al. Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model. Br J Haematol 99 (1997) 344-351
76. Cheson B.D., Bennett J.M., Kantarjian H., et al. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 96 (2000) 3671-3674
77. Cheson B.D., Greenberg P.L., Bennett J.M., et al. Clinical application and proposal for modification of the international working group (IWG) response criteria in myelodysplasia. Blood (2006)
78. Terpos E., Mougiou A., Kouraklis A., et al. Prolonged administration of erythropoietin increases erythroid response rate in myelodysplastic syndromes: a phase II trial in 281 patients. Br J Haematol 118 (2002) 174-180
79. Verhoef G., Van den Berghe H., and Boogaerts M. Cytogenetic effects on cells derived from patients with myelodysplastic syndromes during treatment with hemopoietic growth factors. Leukemia 6 (1992) 766-769
80. Rigolin G.M., Porta M.D., Ciccone M., et al. In patients with myelodysplastic syndromes response to rHuEPO and G-CSF treatment is related to an increase of cytogenetically normal CD34 cells. Br J Haematol 126 (2004) 501-507
81. Ljung T., Back R., and Hellstrom-Lindberg E. Hypochromic red blood cells in low-risk myelodysplastic syndromes: effects of treatment with hemopoietic growth factors. Haematologica 89 (2004) 1446-1453
82. Bennett C.L., Luminari S., Nissenson A.R., et al. Pure red-cell aplasia and epoetin therapy. N Engl J Med 351 (2004) 1403-1408
83. Mannone L., Gardin C., Quarre M.C., et al. High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodysplastic syndrome results of a phase II study. Br J Haematol 133 (2006) 513-519
84. Musto P., Lanza F., Balleari E., et al. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes. Br J Haematol 128 (2005) 204-209
85. Stasi R., Abruzzese E., Lanzetta G., Terzoli E., and Amadori S. Darbepoetin alfa for the treatment of anemic patients with low- and intermediate-1-risk myelodysplastic syndromes. Ann Oncol 16 (2005) 1921-1927
86. Negrin R.S., Stein R., Vardiman J., et al. Treatment of the anemia of myelodysplastic syndromes using recombinant human granulocyte colony-stimulating factor in combination with erythropoietin. Blood 82 (1993) 737-743
87. Negrin R.S., Stein R., Doherty K., et al. Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. Blood 87 (1996) 4076-4081
88. Hellstrom-Lindberg E., Ahlgren T., Beguin Y., et al. Treatment of anemia in myelodysplastic 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 (1998) 68-75
89. Remacha A.F., Arrizabalaga B., Villegas A., et al. Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group. Haematologica 84 (1999) 1058-1064
90. Casadevall N., Durieux P., Dubois S., et al. Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial. Blood 104 (2004) 321-327
91. Balleari E., Rossi E., Clavio M., et al. Erythropoietin plus granulocyte colony-stimulating factor is better than erythropoietin alone to treat anemia in low-risk myelodysplastic syndromes: results from a randomized single-centre study. Ann Hematol 85 (2006) 174-180
92. Bowen D., Hyslop A., Keenan N., et al. Predicting erythroid response to recombinant erythropoietin plus granulocyte colony-stimulating factor therapy following a single subcutaneous bolus in patients with myelodysplasia. Haematologica 91 (2006) 709-710
93. Jadersten M., Montgomery S.M., Dybedal I., Porwit-MacDonald A., and Hellstrom-Lindberg E. Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood 106 (2005) 803-811
94. Jädersten M., Malcovati L., Dybedal I., et al. Treatment with Erythropoietin and G-CSF Improves Survival in MDS Patients with Low Transfusion Need. Blood 106 (2006) 172
95. Park S, Grabar S, Kelaidi C, Beyne-Rauzy O, Picard F, Bardet V et al. Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience. Blood Available online 16 October 2007.
96. Molldrem J.J., Jiang Y.Z., Stetler-Stevenson M., Mavroudis D., Hensel N., and Barrett A.J. Haematological response of patients with myelodysplastic syndrome to antithymocyte globulin is associated with a loss of lymphocyte-mediated inhibition of CFU-GM and alterations in T-cell receptor Vbeta profiles. Br J Haematol 102 (1998) 1314-1322
97. Killick S.B., Mufti G., Cavenagh J.D., et al. A pilot study of antithymocyte globulin (ATG) in the treatment of patients with 'low-risk' myelodysplasia. Br J Haematol 120 (2003) 679-684
98. Stadler M., Germing U., Kliche K.O., et al. A prospective, randomised, phase II study of horse antithymocyte globulin vs rabbit antithymocyte globulin as immune-modulating therapy in patients with low-risk myelodysplastic syndromes. Leukemia 18 (2004) 460-465
99. Aivado M., Rong A., Stadler M., et al. Favourable response to antithymocyte or antilymphocyte globulin in low-risk myelodysplastic syndrome patients with a 'non-clonal' pattern of X-chromosome inactivation in bone marrow cells. Eur J Haematol 68 (2002) 210-216
100. Steensma D.P., Dispenzieri A., Moore S.B., Schroeder G., and Tefferi A. Antithymocyte globulin has limited efficacy and substantial toxicity in unselected anemic patients with myelodysplastic syndrome. Blood 101 (2003) 2156-2158
101. Broliden P.A., Dahl I.M., Hast R., et al. Antithymocyte globulin and cyclosporine A as combination therapy for low-risk non-sideroblastic myelodysplastic syndromes. Haematologica 91 (2006) 667-670
102. Jonasova A., Neuwirtova R., Cermak J., et al. Cyclosporin A therapy in hypoplastic MDS patients and certain refractory anaemias without hypoplastic bone marrow. Br J Haematol 100 (1998) 304-309
103. Shimamoto T., Tohyama K., Okamoto T., et al. Cyclosporin A therapy for patients with myelodysplastic syndrome: multicenter pilot studies in Japan. Leuk Res 27 (2003) 783-788
104. D'Amato R.J., Loughnan M.S., Flynn E., and Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A 91 (1994) 4082-4085
105. Raza A., Meyer P., Dutt D., et al. Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes. Blood 98 (2001) 958-965
106. Musto P., Falcone A., Sanpaolo G., Bisceglia M., Matera R., and Carella A.M. Thalidomide abolishes transfusion-dependence in selected patients with myelodysplastic syndromes. Haematologica 87 (2002) 884-886
107. Strupp C., Germing U., Aivado M., Misgeld E., Haas R., and Gattermann N. Thalidomide for the treatment of patients with myelodysplastic syndromes. Leukemia 16 (2002) 1-6
108. List A., Kurtin S., Roe D.J., et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 352 (2005) 549-557
109. List A., Dewald G., Bennett J., et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 355 (2006) 1456-1465
110. Raza A, Reeves JA, Feldman EJ, Dewald GW, Bennett JM, Deeg HJ et al. Phase II study of lenalidomide in transfusion-dependent, low- and intermediate-1-risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood Available online 24 September 2007.
111. Gersuk G.M., Beckham C., Loken M.R., et al. A role for tumour necrosis factor-alpha, Fas and Fas-Ligand in marrow failure associated with myelodysplastic syndrome. Br J Haematol 103 (1998) 176-188
112. Maciejewski J.P., Risitano A.M., Sloand E.M., et al. A pilot study of the recombinant soluble human tumour necrosis factor receptor (p75)-Fc fusion protein in patients with myelodysplastic syndrome. Br J Haematol 117 (2002) 119-126
113. Raza A., Candoni A., Khan U., et al. Remicade as TNF suppressor in patients with myelodysplastic syndromes. Leuk Lymphoma 45 (2004) 2099-2104
114. Bellamy W.T., Richter L., Sirjani D., et al. Vascular endothelial cell growth factor is an autocrine promoter of abnormal localized immature myeloid precursors and leukemia progenitor formation in myelodysplastic syndromes. Blood 97 (2001) 1427-1434
115. Giles F.J., Stopeck A.T., Silverman L.R., et al. SU5416, a small molecule tyrosine kinase receptor inhibitor, has biologic activity in patients with refractory acute myeloid leukemia or myelodysplastic syndromes. Blood 102 (2003) 795-801
116. TM) in Patients with Myelodysplastic Syndrome (MDS). Blood 100 (2002) 3119a
117. Bonati A., Rizzoli V., and Lunghi P. Arsenic trioxide in hematological malignancies: the new discovery of an ancient drug. Curr Pharm Biotechnol 7 (2006) 397-405
118. Schiller G.J., Slack J., Hainsworth J.D., et al. Phase II multicenter study of arsenic trioxide in patients with myelodysplastic syndromes. J Clin Oncol 24 (2006) 2456-2464
119. Vey N., Bosly A., Guerci A., et al. Arsenic trioxide in patients with myelodysplastic syndromes: a phase II multicenter study. J Clin Oncol 24 (2006) 2465-2471
120. Silverman L.R., Demakos E.P., Peterson B.L., et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 20 (2002) 2429-2440
121. Wijermans P., Lubbert M., Verhoef G., et al. Low-dose 5-aza-2'-deoxycytidine, a DNA hypomethylating agent, for the treatment of high-risk myelodysplastic syndrome: a multicenter phase II study in elderly patients. J Clin Oncol 18 (2000) 956-962
122. Kantarjian H., Issa J.P., Rosenfeld C.S., et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 106 (2006) 1794-1803
123. Graef T., Kuendgen A., Fenk R., Zohren F., Haas R., and Kobbe G. Successful treatment of relapsed AML after allogeneic stem cell transplantation with azacitidine. Leuk Res 31 (2007) 257-259
124. Kantarjian H., Oki Y., Garcia-Manero G., et al. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 109 (2007) 52-57
125. Khan R., Aggerholm A., Hokland P., Hassan M., and Hellstrom-Lindberg E. A pharmacodynamic study of 5-azacytidine in the P39 cell line. Exp Hematol 34 (2006) 35-43
126. Bhalla K., and List A. Histone deacetylase inhibitors in myelodysplastic syndrome. Best Pract Res Clin Haematol 17 (2004) 595-611
127. Kuendgen A., Knipp S., Fox F., et al. Results of a phase 2 study of valproic acid alone or in combination with all-trans retinoic acid in 75 patients with myelodysplastic syndrome and relapsed or refractory acute myeloid leukemia. Ann Hematol 84 Suppl 13 (2005) 61-66
128. Germing U., Strupp C., Kuendgen A., et al. Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes. Haematologica/the Hematology Journal 91 (2006) 1596-1604
129. Kurzrock R., Kantarjian H.M., Cortes J.E., et al. Farnesyltransferase inhibitor R115777 in myelodysplastic syndrome: clinical and biologic activities in the phase 1 setting. Blood 102 (2003) 4527-4534
130. Kurzrock R., Albitar M., Cortes J.E., et al. Phase II study of R115777, a farnesyl transferase inhibitor, in myelodysplastic syndrome. J Clin Oncol 22 (2004) 1287-1292
131. Apperley J.F., Gardembas M., Melo J.V., et al. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 347 (2002) 481-487
132. Navas T.A., Mohindru M., Estes M., et al. Inhibition of overactivated p38 MAPK can restore hematopoiesis in myelodysplastic syndrome progenitors. Blood 108 (2006) 4170-4177
133. Stofega M.R., Cheng M., Ma H., et al. TelintraTM (TLK199) Enhances Granulocyte Colony-Stimulating Factor Production. Blood 108 (2006) 1161a
134. Chan G., DiVenuti G., and Miller K. Danazol for the treatment of thrombocytopenia in patients with myelodysplastic syndrome. Am J Hematol 71 (2002) 166-171
135. Yamada T., Tsurumi H., Kasahara S., Hara T., Sawada M., and Moriwaki H. Immunosuppressive therapy for myelodysplastic syndrome: efficacy of methylprednisolone pulse therapy with or without cyclosporin A. J Cancer Res Clin Oncol 129 (2003) 485-491
136. Kaushansky K., Lok S., Holly R.D., et al. Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin. Nature 369 (1994) 568-571
137. Newland A., Caulier M.T., Kappers-Klunne M., et al. An open-label, unit dose-finding study of AMG 531, a novel thrombopoiesis-stimulating peptibody, in patients with immune thrombocytopenic purpura. Br J Haematol 135 (2006) 547-553