Treatment of Low-Risk Myelodysplastic Syndrome: Hematopoietic Growth Factors Erythropoietins and Thrombopoietins

Seminars in Hematology

Volumn 49, Issue 4, 2012, Pages 295-303

  Santini, Valeria ^a  

^a UNIVERSITY OF FLORENCE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

AZACITIDINE; DIHYDROXYCOLECALCIFEROL; ELTROMBOPAG; HEMOGLOBIN; ISOTRETINOIN; LENALIDOMIDE; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; PLACEBO; RECOMBINANT ERYTHROPOIETIN; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; RECOMBINANT GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; RECOMBINANT INTERLEUKIN 3; RECOMBINANT THROMBOPOIETIN; RETINOIC ACID; ROMIPLOSTIM;

ACUTE GRANULOCYTIC LEUKEMIA; ANEMIA; ARTICLE; BLEEDING; BLOOD TRANSFUSION; CARDIOVASCULAR DISEASE; COMBINATION CHEMOTHERAPY; CONSENSUS DEVELOPMENT; CYTOPENIA; DEEP VEIN THROMBOSIS; DRUG APPROVAL; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG USE; DRUG WITHDRAWAL; EVIDENCE BASED MEDICINE; HEMATOLOGIC MALIGNANCY; HEMOGLOBIN BLOOD LEVEL; HUMAN; HYPERTENSION; IDIOPATHIC THROMBOCYTOPENIC PURPURA; KIDNEY FAILURE; LOW DRUG DOSE; MALIGNANT TRANSFORMATION; META ANALYSIS (TOPIC); MORTALITY; MULTIPLE CYCLE TREATMENT; MYELODYSPLASTIC SYNDROME; MYELOFIBROSIS; NONHUMAN; OVERALL SURVIVAL; PATIENT SELECTION; PHASE 3 CLINICAL TRIAL (TOPIC); POLYCYTHEMIA; PRACTICE GUIDELINE; PRIORITY JOURNAL; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIAL (TOPIC); RISK BENEFIT ANALYSIS; SEIZURE; SOLID TUMOR; SYSTEMATIC REVIEW (TOPIC); THROMBOCYTE TRANSFUSION; THROMBOCYTOPENIA; THROMBOSIS; TREATMENT DURATION; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT;

ERYTHROPOIETIN; HUMANS; MYELODYSPLASTIC SYNDROMES; THROMBOPOIETIN;

EID: 84867622112     PISSN: 00371963     EISSN: 15328686     Source Type: Journal    
DOI: 10.1053/j.seminhematol.2012.09.003     Document Type: Article

References (74)

1. Greenberg P.L., Cox C., LeBeau M.M., et al. International scoring system for evaluating prognosis in MDS. Blood 1997, 89:2079-2088.
2. Greenberg P.L., Tuechler H., Schanz J., et al. Revised International Prognostic Scoring System (IPPS-R) for myelodysplastic syndromes. Blood 2012, 120:2454-2465.
3. Malcovati L., Della Porta M.G., Strupp C., et al. Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based Prognostic Scoring System (WPSS). Haematologica 2011, 96:1433-1440.
4. Corey S.J., Minden M.D., Barber D.L., Kantarjian H., Wang J.C., Schimmer A.D. Myelodysplastic syndromes: the complexity of stem-cell diseases. Nat Rev Cancer 2007, 7:118-129.
5. Hoefsloot L.H., van Amelsvoort M.P., Broeders L.C., et al. Erythropoietin-induced activation of STAT5 is impaired in the myelodysplastic syndrome. Blood 1997, 89:1690-1700.
6. Mittelman M., Gardyn J., Carmel M., Malovani H., Barak Y., Nir U. Analysis of the erythropoietin receptor gene in patients with myeloproliferative and myelodysplastic syndromes. Leuk Res 1996, 20:459-466.
7. Shimizu R., Komatsu N., Miura Y. Dominant negative effect of a truncated erythropoietin receptor (EPOR-T) on erythropoietin-induced erythroid differentiation: possible involvement of EPOR-T in ineffective erythropoiesis of myelodysplastic syndrome. Exp Hematol 1999, 27:229-233.
8. Fontenay-Roupie M., Bouscary D., Guesnu M., et al. Ineffective erythropoiesis in myelodysplastic syndromes: correlation with Fas expression but not with lack of erythropoietin receptor signal transduction. Br J Haematol 1999, 106:464-473.
9. Navas T.A., Mohindru M., Estes M., et al. Inhibition of overactivated p38 MAPK can restore hematopoiesis in myelodysplastic syndrome progenitors. Blood 2006, 108:4170-4177.
10. Frisan E., Pawlikowska P., Pierre-Eugene C., et al. p-ERK1/2 is a predictive factor of response to erythropoiesis-stimulating agents in low/int-1 myelodysplastic syndromes. Haematologica 2010, 95:1964-1968.
11. Spinelli E., Caporale R., Buchi F., et al. Distinct signal transduction abnormalities and erythropoietin response in bone marrow hematopoietic cell subpopulations of myelodysplastic syndrome patients. Clin Cancer Res 2012, 18:3079-3089.
12. Ma W., Kantarjian H., Zhang K., et al. Significant association between polymorphism of the erythropoietin gene promoter and myelodysplastic syndrome. BMC Med Genet 2010, 16:11. 163.
13. Tefferi A., Vardiman J.W. Myelodysplastic syndromes. N Engl J Med 2009, 361:1872-1885.
14. Oliva E.N., Finelli C., Santini V., et al. Quality of life and physicians' perception in myelodysplastic syndromes. Am J Blood Res 2012, 2:136-147.
15. Nilsson-Ehle H., Birgegård G., Samuelsson J., et al. Quality of life, physical function and MRI T2* in elderly low-risk MDS patients treated to a haemoglobin level of ≥120 g/L with darbepoetin alfa ± filgrastim or erythrocyte transfusions. Eur J Haematol 2011, 87:244-252.
16. Davidoff A.J., Smith S.W., Baer M.R., et al. Patient and physician characteristics associated with erythropoiesis-stimulating agent use in patients with myelodysplastic syndromes. Haematologica 2012, 97:128-132.
17. Ross S.D., Allen I.E., Probst C.A., et al. Efficacy and safety of erythropoiesis-stimulating proteins in myelodysplastic syndrome: a systematic review and meta-analysis. Oncologist 2007, 12:1264-1273.
18. Moyo V., Lefebvre P., Duh M.S., et al. Erythropoiesis-stimulating agents in the treatment of anemia in myelodysplastic syndromes: a meta-analysis. Ann Hematol 2008, 87:527-536.
19. Mundle S., Lefebvre P., Vekeman F., et al. An assessment of erythroid response to epoetin alpha as a single agent versus in combination with granulocyte- or granulocyte-macrophage-colony-stimulating factor in myelodysplastic syndromes using a meta-analysis approach. Cancer 2009, 115:706-715.
20. Gabrilove J.L., Cleeland C.S., Livingston R.B. Clinical evaluation of once-weekly dosing of epoetin alfa in chemotherapy patients: improvements in hemoglobin and quality of life are similar to three-times-weekly dosing. J Clin Oncol 2001, 19:2875-2882.
21. Straus D.J., Testa M.A., Sarokhan B.J., et al. Quality-of-life and health benefits of early treatment of mild anemia: a randomized trial of epoetin alfa in patients receiving chemotherapy for hematologic malignancies. Cancer 2006, 107:1909-1917.
22. Stasi R., Brunetti M., Terzoli E., Abruzzese E., Amadori S. Once-weekly dosing of recombinant human erythropoietin alpha in patients with myelodysplastic syndromes unresponsive to conventional dosing. Ann Oncol 2004, 15:1684-1690.
23. Aloe Spiriti M.A., Latagliata R., Niscola P., et al. Impact of a new dosing regimen of epoetin alfa on quality of life and anemia in patients with low-risk myelodysplastic syndrome. Ann Hematol 2005, 84:167-176.
24. Park S., Kelaidi C., Sapena R., et al. Early introduction of ESA in low risk MDS patients may delay the need for RBC transfusion: a retrospective analysis on 112 patients. Leuk Res 2010, 34:1430-1436.
25. Latagliata R., Oliva E.N., Volpicelli P., et al. Twice-weekly high-dose rHuEpo for the treatment of anemia in patients with low-risk myelodysplastic syndromes. Acta Haematol 2008, 120:104-107.
26. Azzarà A., Carulli G., Galimberti S., et al. High-dose (40,000 IU twice/week) alpha recombinant human erythropoietin as single agent in low/intermediate risk myelodysplastic syndromes: a retrospective investigation on 133 patients treated in a single institution. Am J Hematol 2011, 86:762-767.
27. Balleari E., Clavio M., Arboscello E., et al. Weekly standard doses of rh-EPO are highly effective for the treatment of anemic patients with low-intermediate 1 risk myelodysplastic syndromes. Leuk Res 2011, 35:1472-1476.
28. Gotlib J., Lavori P., Quesada S., et al. A phase II intra-patient dose-escalation trial of weight-based darbepoetin alfa with or without granulocyte-colony stimulating factor in myelodysplastic syndromes. Am J Hematol 2009, 8:15-20.
29. Gabrilove J., Paquette R., Lyons R.M., et al. Phase 2, single-arm trial to evaluate the effectiveness of darbepoetin alfa for correcting anaemia in patients with myelodysplastic syndromes. Br J Haematol 2008, 142:379-393.
30. Kelaidi C., Fenaux P. Darbepoetin alfa in anemia of myelodysplastic syndromes: present and beyond. Expert Opin Biol Ther 2010, 10:605-614.
31. Oliva E.N., Nobile F., Alimena G., et al. Darbepoetin alfa for the treatment of anemia associated with myelodysplastic syndromes: efficacy and quality of life. Leuk Lymphoma 2010, 51:1007-1014.
32. Villegas A., Arrizabalaga B., Fernández-Lago C., et al. Darbepoetin alfa for anemia in patients with low or intermediate-1 risk myelodysplastic syndromes and positive predictive factors of response. Curr Med Res Opin 2011, 27:951-960.
33. 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 2002, 118:174-180.
34. 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 2006, 85:174-180.
35. Kasper C., Zahner J., Sayer H.G. Recombinant human erythropoietin in combined treatment with granulocyte- or granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. J Cancer Res Clin Oncol 2002, 128:497-502.
36. Greenberg P.L., Sun Z., Miller K.B., et al. Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996). Blood 2009, 114:2393-2400.
37. Stasi R., Brunetti M., Terzoli E., et al. Sustained response to recombinant human erythropoietin and intermittent all-trans retinoic acid in patients with myelodysplastic syndromes. Blood 2002, 99:1578-1584.
38. Itzykson R., Ayari S., Vassilief D., et al. Is there a role for all-trans retinoic acid in combination with recombinant erythropoetin in myelodysplastic syndromes?. A report on 59 cases. Leukemia 2009, 23:673-678.
39. Ferrero D., Darbesio A., Giai V., et al. Efficacy of a combination of human recombinant erythropoietin + 13-cis-retinoic acid and dihydroxylated vitamin D3 to improve moderate to severe anaemia in low/intermediate risk myelodysplastic syndromes. Br J Haematol 2009, 144:342-349.
40. Crisà E., Foli C., Passera R., et al. Long-term follow-up of myelodysplastic syndrome patients with moderate/severe anaemia receiving human recombinant erythropoietin + 13-cis-retinoic acid and dihydroxylated vitamin D3: independent positive impact of erythroid response on survival. Br J Haematol 2012, 158:99-107.
41. Komrokji R.S., Lancet J.E., Swern A.S., et al. Combined treatment with lenalidomide and epoetin alfa in lower risk patients with myelodysplastic syndrome. Blood 2012 Aug 30, [Epub ahead of print].
42. Santini V., Gozzini A., Lunghi T., et al. Azacitidine in combination with EPO plus G-CSF and Valproic acid rapidly determines hematological improvement in pretreated non responsive IPSS INT-1 MDs patients. Leuk Res 2007, 31(suppl 1). abstract 151.
43. Itzykson R., Thépot S., Beyne-Rauzy O., et al. Does addition of erythropoiesis stimulating agents improve the outcome of higher-risk myelodysplastic syndromes treated with azacitidine?. Leuk Res 2012, 36:397-400.
44. Mittelman M. AZA-ESA combo: a new standard for higher risk MDS?. Leuk Res 2012, 36:389-391.
45. Musto P., Falcone A., Sanpaolo G., et al. Combination of erythropoietin and thalidomide for the treatment of anemia in patients with myelodysplastic syndromes. Leuk Res 2006, 30:385-388.
46. Grossi A., Musto P., Santini V., et al. Combined therapy with amifostine plus erythropoietin for the treatment of myelodysplastic syndromes. Haematologica 2002, 87:322-323.
47. Dicato M., Plawny L. Erythropoietin in cancer patients: pros and cons. Curr Opin Oncol 2010, 22:307-311.
48. Jadersten M., Malcovati L., Dybedal I., et al. Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol 2008, 26:3607-3613.
49. Musto P., Villani O., Martorelli M.C., et al. Response to recombinant erythropoietin alpha, without the adjunct of granulocyte-colony stimulating factor, is associated with a longer survival in patients with transfusion-dependent myelodysplastic syndromes. Leuk Res 2010, 34:981-985.
50. Park S., Grabar S., Kelaidi C., et al. Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience. Blood 2008, 111:574-582.
51. Steensma D.P. Prospects and perils of retrospective risk assessment of erythropoiesis-stimulating agents. Am J Hematol 2008, 83:693-694.
52. Smith S.W., Sato M., Gore S.D., et al. Erythropoiesis-stimulating agents are not associated with increased risk of thrombosis in patients with myelodysplastic syndromes. Haematologica 2012, 97:15-20.
53. Hellström-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 2003, 120:1037-1046.
54. Westers T.M., Alhan C., Chamuleau M.E., et al. Aberrant immunophenotype of blasts in myelodysplastic syndromes is a clinically relevant biomarker in predicting response to growth factor treatment. Blood 2010, 115:1779-1784.
55. Santini V., Alessandrino P.E., Angelucci E., et al. Clinical management of myelodysplastic syndromes: update of SIE, SIES, GITMO practice guidelines. Leuk Res 2010, 34:1576-1588.
56. Greenberg P.L., Attar E., Bennett J.M., et al. NCCN clinical practice guidelines in oncology: myelodysplastic syndromes. J Natl Compr Canc Netw 2011, 9:30-56.
57. Rizzo J.D., Somerfield M.R., Hagerty K.L., et al. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update. Blood 2008, 111:25-41.
58. Bryan J., Jabbour E., Prescott H., et al. Thrombocytopenia in patients with myelodysplastic syndromes. Semin Hematol 2010, 47:274-280.
59. Bussel J.B., Kuter D.J., George J.N., et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med 2006, 355:1672-1681.
60. Lawrence S. Amgen's TPO mimic faces stiff competition. Nat Biotechnol 2006, 24:1044.
61. Tiu R.V., Sekeres M.A. The role of AMG-531 in the treatment of thrombocytopenia in idiopathic thrombocytopenic purpura and myelodysplastic syndromes. Expert Opin Biol Ther 2008, 8:1021-1030.
62. Kantarjian H., Fenaux P., Sekeres M.A., et al. Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia. J Clin Oncol 2010, 28:437-444.
63. Kantarjian H.M., Giles F.J., Greenberg P.L., et al. Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Blood 2010, 116:3163-3170.
64. Sekeres M.A., Kantarjian H., Fenaux P., et al. Subcutaneous or intravenous administration of romiplostim in thrombocytopenic patients with lower risk myelodysplastic syndromes. Cancer 2011, 117:992-1000.
65. Gardner K., Mathe S., Sahu S. Leukaemic transformation with romiplostim. Br J Haematol 2012, 158:153.
66. Fenaux P., Kantarjian H.M., Muus P., et al. Update of an open-label extension study evaluating the long-term safety and efficacy of romiplostim in thrombocytopenic patients with myelodysplastic syndromes (MDS). Blood (ASH Annual Meeting Abstracts) 2011, 118:2772.
67. Giagounidis A., Mufti G.J., Kantarjian H.M., et al. Treatment with the thrombopoietin (TPO)-receptor agonist romiplostim in thrombocytopenic patients (Pts) with low or intermediate-1 (Int-1) risk myelodysplastic syndrome (MDS): results of a randomized, double-blind, placebo (PBO)-controlled study. Blood (ASH Annual Meeting Abstracts) 2011, 118:117.
68. Greenberg P.L., Garcia-Manero G., Moore M., et al. A randomized controlled trial of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome (MDS) receiving decitabine. Leuk Lymphoma 2012 Aug 20, [Epub ahead of print].
69. Sharma V., Randhawa H., Sharma A., et al. Eltrombopag-an oral thrombopoietin agonist. Eur Rev Med Pharmacol Sci 2012, 16:743-746.
70. Garnock-Jones K.P. Eltrombopag: a review of its use in treatment-refractory chronic primary immune thrombocytopenia. Drugs 2011, 71:1333-1337.
71. Will B., Kawahara M., Luciano J.P., et al. Effect of the nonpeptide thrombopoietin receptor agonist Eltrombopag on bone marrow cells from patients with acute myeloid leukemia and myelodysplastic syndrome. Blood 2009, 114:3899-3908.
72. Roth M., Will B., Simkin G., Narayanagari S., et al. Eltrombopag inhibits the proliferation of leukemia cells via reduction of intracellular iron and induction of differentiation. Blood 2012, 120:386-394.
73. Oliva E., Latagliata R., Santini V., et al. Efficacy and safety of eltrombopag for the treatment of thrombocytopenia of low and INT-1 MDS: preliminary results of a prospective randomized, single-blind placebo controlled trial. Haematologica 2012, 97(supp1 470). [abstract 1138].
74. Olnes M.J., Scheinberg P., Calvo K.R., et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med 2012, 367:11-19.