Current and novel therapeutic approaches in myelodysplastic syndromes

Journal of Community and Supportive Oncology

Volumn 12, Issue 7, 2014, Pages 236-249

  Estephan, Fayez ^a   Tiu, Ramon V ^a  

^a TAUSSIG CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOPEPTIDASE INHIBITOR; ANTIANEMIC AGENT; ANTIBIOTIC AGENT; AZACITIDINE; BELINOSTAT; CANCER GROWTH FACTOR; CYCLOSPORIN A; DECITABINE; ENTINOSTAT; EZATIOSTAT; GLUTATHIONE TRANSFERASE; HEMOPOIETIC GROWTH FACTOR; LENALIDOMIDE; MAMMALIAN TARGET OF RAPAMYCIN INHIBITOR; MOMELOTINIB; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; PANOBINOSTAT; PRACINOSTAT; RECOMBINANT ERYTHROPOIETIN; RUXOLITINIB; THYMOCYTE ANTIBODY; TOSEDOSTAT; TRANSFORMING GROWTH FACTOR BETA; VORINOSTAT;

CHROMOSOMAL INSTABILITY; CHRONIC MYELOMONOCYTIC LEUKEMIA; CYTOGENETICS; CYTOPENIA; DISEASE COURSE; DNA METHYLATION; DNA REPAIR; ERYTHROCYTE TRANSFUSION; ERYTHROID CELL; FLUORESCENCE IN SITU HYBRIDIZATION; GASTROINTESTINAL HEMORRHAGE; GENE MUTATION; HEMATOPOIETIC CELL; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; IRON CHELATION; MONOSOMY 7; MYELODYSPLASTIC SYNDROME; MYELOPROLIFERATIVE NEOPLASM; OVERALL SURVIVAL; PATHOPHYSIOLOGY; PHASE 2 CLINICAL TRIAL (TOPIC); REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SOMATIC MUTATION; SYSTEMATIC REVIEW (TOPIC); TRISOMY 8;

EID: 84991688432     PISSN: 23307749     EISSN: None     Source Type: Journal    
DOI: 10.12788/jcso.0057     Document Type: Review

References (87)

1. Teferi A, Vardiman JW. Myelodysplastic syndromes. N Engl J Med. 2009;361:1872-1885.
2. Sekeres MA. Epidemiology, natural history, and practice patterns of patients with myelodysplastic syndromes in 2010. J Natl Compr Canc Netw. 2011;9:57-63.
3. Ma X, Does M, Raza A, Mayne ST. Myelodysplastic syndromes: incidence and survival in the United States. Cancer. 2007;109:1536-1542.
4. Abdel-Wahab O. Molecular genetics of acute myeloid leukemia: clinical implications and opportunities for integrating genomics into clinical practice. Hematology. 2012;17(suppl 1):39S-42S.
5. Mohamedali A, Gaken J, Twine NA, et al. Prevalence and prognostic signifcance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes. Blood. 2007;110:3365-3373.
6. Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modifcation of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006;108:419-425.
7. Papaemmanuil E, Gerstung M, Malcovati L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013;122:3616-3627.
8. Tol F, Kade S, Schlarmann C, et al. Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes. Blood. 2012;119:3578-3584.
9. Visconte V, Rogers HJ, Singh J, et al. SF3B1 haploinsufciency leads to formation of ring sideroblasts in myelodysplastic syndromes. Blood. 2012;120:3173-3186.
10. Visconte V, Makishima H, Jankowska A, et al. SF3B1, a splicing factor is frequently mutated in refractory anemia with ring sideroblasts. Leukemia. 2012;26:542-545.
11. Visconte V, Makishima H, Maciejewski JP, Tiu RV. Emerging roles of the spliceosomal machinery in myelodysplastic syndromes and other hematological disorders. Leukemia. 2012;26:2447-2454.
12. Raza A, Galili N. Te genetic basis of phenotypic heterogeneity in myelodysplastic syndromes. Nat Rev Cancer. 2012;12:849-859.
13. Tiu RV, Visconte V, Traina F, Schwandt A, Maciejewski JP. Updates in cytogenetics and molecular markers in MDS. Curr Hematol Malig Rep. 2011;6:126-135.
14. Gondek LP, Tiu R, O'Keefe CL, Sekeres MA, Teil KS, Maciejewski JP. Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML. Blood. 2008;111:1534-1542.
15. Tiu RV, Gondek LP, O'Keefe CL, et al. Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies. Blood. 2011;117:4552-4560.
16. Epling-Burnette PK, Bai F, Painter JS, et al. Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors. Blood. 2007;109:4816-4824.
17. Goyal R, Qawi H, Ali I, et al. Biologic characteristics of patients with hypocellular myelodysplastic syndromes. Leuk Res. 1999;23:357-364.
18. Aizawa S, Nakano M, Iwase O, et al. Bone marrow stroma from refractory anemia of myelodysplastic syndrome is defective in its ability to support normal CD34-positive cell proliferation and diferentiation in vitro. Leuk Res. 1999;23:239-246.
19. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classifcation of the myelodysplastic syndromes. Br J Haematol. 1982;51:189-199.
20. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classifcation of the acute leukaemias. French-American-British (FAB) cooperative group. Br J Haematol. 1976;33:451-458.
21. Germing U, Kundgen A. Prognostic scoring systems in MDS. Leuk Res. 2012;36:1463-1469.
22. Varela BL, Chuang C, Woll JE, Bennett JM. Modifcations in the classifcation of primary myelodysplastic syndromes: the addition of a scoring system. Hematol Oncol. 1985;3:55-63.
23. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079-2088.
24. Morel P, Hebbar M, Lai JL, et al. Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases. Leukemia. 1993;7:1315-1323.
25. Toyama K, Ohyashiki K, Yoshida Y, et al. Clinical implications of chromosomal abnormalities in 401 patients with myelodysplastic syndromes: a multicentric study in Japan. Leukemia. 1993;7:499-508.
26. Zeidan AM, Smith BD, Komrokji RS, Gore SD. Prognostication in myelodysplastic syndromes: beyond the International Prognostic Scoring System (IPSS). Am J Med. 2013;126:e25.
27. Bejar R, Stevenson KE, Caughey BA, et al. Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes. J Clin Oncol. 2012;30:3376-3382.
28. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120:2454-2465.
29. Malcovati L, Porta MG, Pascutto C, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classifed according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005;23:7594-7603.
30. Greenberg PL. Current therapeutic approaches for patients with myelodysplastic syndromes. Br J Haematol. 2010;150:131-143.
31. Santini V. Clinical use of erythropoietic stimulating agents in myelodysplastic syndromes. Oncologist. 2011;16(suppl 3):35S-42S.
32. Casadevall N, Durieux P, Dubois S, et al. Health, economic, and quality-of-life efects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial. Blood. 2004;104:321-327.
33. Greenberg PL, Sun Z, Miller KB, 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.
34. Greenberg PL, Attar E, Bennett JM, et al. NCCN Clinical Practice Guidelines in Oncology: myelodysplastic syndromes. J Natl Compr Canc Netw. 2011;9:30-56.
35. Gabrilove J, Paquette R, Lyons RM, et al. Phase 2, single-Arm trial to evaluate the efectiveness of darbepoetin alfa for correcting anaemia in patients with myelodysplastic syndromes. Br J Haematol. 2008;142:379-393.
36. Smith SW, Sato M, Gore SD, et al. Erythropoiesis-stimulating agents are not associated with increased risk of thrombosis in patients with myelodysplastic syndromes. Haematologica. 2012;97:15-20.
37. 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.
38. Davidof AJ, Weiss Smith S, Baer MR, et al. Patient and physician characteristics associated with erythropoiesis-stimulating agent use in patients with myelodysplastic syndromes. Haematologica. 2012;97:128-132.
39. Bejar R, Levine R, Ebert BL. Unraveling the molecular pathophysiology of myelodysplastic syndromes. J Clin Oncol. 2011;29:504-515.
40. List A, Dewald G, Bennett J, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006;355:1456-1465.
41. Fenaux P, Giagounidis A, Selleslag D, et al. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood. 2011;118:3765-3776.
42. Raza A, Reeves JA, Feldman EJ, et al. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008 ;111:86-93.
43. Ades L, Boehrer S, Prebet T, et al. Efcacy and safety of lenalidomide in intermediate-2 or high-risk myelodysplastic syndromes with 5q deletion: results of a phase 2 study. Blood. 2009;113:3947-3952.
44. Sloand EM, Wu CO, Greenberg P, Young N, Barrett J. Factors afecting response and survival in patients with myelodyspla-sia treated with immunosuppressive therapy. J Clin Oncol. 2008;26:2505-2511.
45. Saunthararajah Y. Key clinical observations after 5-Azacytidine and decitabine treatment of myelodysplastic syndromes suggest practical solutions for better outcomes. Hematology Am Soc Hematol Educ Program. 2013;2013:511-521.
46. Scott BL, Sandmaier BM, Storer B, et al. Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia. 2006;20:128-135.
47. Jiang Y, Dunbar A, Gondek LP, et al. Aberrant DNA methylation is a dominant mechanism in MDS progression to AML. Blood. 2009;113:1315-1325.
48. Grifths EA, Gore SD. DNA methyltransferase and histone deacetylase inhibitors in the treatment of myelodysplastic syndromes. Semin Hematol. 2008;45:23-30.
49. Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006;106:1794-1803.
50. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efcacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, openlabel, phase III study. Lancet Oncol. 2009;10:223-232.
51. Silverman LR, Demakos EP, Peterson BL, 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. 2002;20:2429-2440.
52. Silverman LR. Hypomethylating agents in myelodysplastic syndromes changing the inevitable: the value of azacitidine as maintenance therapy, efects on transfusion and combination with other agents. Leuk Res. 2009;33(suppl 2):18S-21S.
53. Kantarjian HM, O'Brien S, Huang X, et al. Survival advantage with decitabine versus intensive chemotherapy in patients with higher risk myelodysplastic syndrome: comparison with historical experience. Cancer. 2007;109:1133-1137.
54. Lyons RM, Cosgrif TM, Modi SS, et al. Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol. 2009;27:1850-1856.
55. Steensma DP, Baer MR, Slack JL, et al. Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. J Clin Oncol. 2009;27:3842-3848.
56. Lubbert M, Suciu S, Baila L, et al. Low-dose decitabine versus best supportive care in elderly patients with intermediate-or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: fnal results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol. 2011;29:1987-1996.
57. Prebet T, Gore SD, Esterni B, et al. Outcome of high-risk myelodysplastic syndrome after azacitidine treatment failure. J Clin Oncol. 2011;29:3322-3327.
58. Fenaux P, Bowen D, Gattermann N, et al. Practical use of azacitidine in higher-risk myelodysplastic syndromes: an expert panel opinion. Leuk Res. 2010;34:1410-1416.
59. Steensma DP, Stone RM. Practical recommendations for hypomethylating agent therapy of patients with myelodysplastic syndromes. Hematol Oncol Clin North Am. 2010;24:389-406.
60. Steensma DP. Art of oncology: new voices wanted. J Clin Oncol. 2011;29:3343-3344.
61. Garcia-Manero G. Myelodysplastic syndromes: 2011 update on diagnosis, risk-stratifcation, and management. Am J Hematol. 2011;86:490-498.
62. Knipp S, Hildebrand B, Kundgen A, et al. Intensive chemotherapy is not recommended for patients aged >60 years who have myelodysplastic syndromes or acute myeloid leukemia with high-risk karyotypes. Cancer. 2007;110:345-352.
63. Yang H, Hoshino K, Sanchez-Gonzalez B, Kantarjian H, Garcia-Manero G. Antileukemia activity of the combination of 5-Aza-2'-deoxycytidine with valproic acid. Leuk Res. 2005;29:739-748.
64. Navas T, Zhou L, Estes M, et al. Inhibition of p38alpha MAPK disrupts the pathological loop of proinfammatory factor production in the myelodysplastic syndrome bone marrow microenvironment. Leuk Lymphoma. 2008;49:1963-1975.
65. Sokol L, Cripe L, Kantarjian H, et al. Randomized, dose-escalation study of the p38alpha MAPK inhibitor SCIO-469 in patients with myelodysplastic syndrome. Leukemia. 2013;27:977-980.
66. Garcia-Manero G, Sekeres MA, List AF, et al. Phase 1 Dose-escalation/expansion study of the p38/Tie2 inhibitor ARRY-614 in patients with IPSS low/Int-1 risk myelodysplastic syndromes [ASH abstract 387]. Blood. 2013:122.
67. Verma A, List AF. Cytokine targets in the treatment of myelodysplastic syndromes. Curr Hematol Rep. 2005;4:429-435.
68. Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC. Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat Med. 2005;11:312-319.
69. Lowenberg B, Morgan G, Ossenkoppele GJ, et al. Phase I/II clinical study of Tosedostat, an inhibitor of aminopeptidases, in patients with acute myeloid leukemia and myelodysplasia. J Clin Oncol. 2010;28:4333-4338.
70. Kobune M, Takimoto R, Murase K, et al. Drug resistance is dramatically restored by hedgehog inhibitors in CD34+ leukemic cells. Cancer Sci. 2009;100:948-955.
71. Jamieson C, Cortes JE, Oehler V, et al. Phase 1 dose-eEscalation study of PF-04449913, an oral Hedgehog (Hh) inhibitor, in patients with select hematologic malignancies [ASH abstract 424]. Blood. 2011;118:424.
72. Kantarjian HM, Mufti GJ, Fenaux P, 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): Follow-up AML and survival results of a randomized, double-blind, placebo (PBO)-controlled study [ASH abstract 421]. Blood. 2012;120:421.
73. Oliva EN, Santini V, Zini G, et al. Efcacy and safety of eltrombopag for the treatment of thrombocytopenia of low and intermediate-1 IPSS risk myelodysplastic syndromes: interim analysis of a prospective, randomized, single-blind, placebo-controlled trial (EQoL-MDS) [ASH abstract 923]. Blood. 2012;120:923.
74. Sekeres MA, 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.
75. Sonbol MB, Firwana B, Zarzour A, Morad M, Rana V, Tiu RV. Comprehensive review of JAK inhibitors in myeloproliferative neoplasms. Ter Adv Hematol. 2013;4:15-35.
76. Galili N, Tamayo P, Botvinnik OB, et al. Prediction of response to therapy with ezatiostat in lower risk myelodysplastic syndrome. J Hematol Oncol. 2012;5:20.
77. Raza A, Galili N, Smith SE, et al. A phase 2 randomized multicenter study of 2 extended dosing schedules of oral ezatiostat in low to intermediate-1 risk myelodysplastic syndrome. Cancer. 2012;118:2138-2147.
78. Chapman CM, Sun X, Roschewski M, et al. ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Clin Cancer Res. 2012;18:1979-1991.
79. Raza A, Greenberg PL, Olnes MJ, Silverman LR, Wilhelm F. Final phase I/II results of rigosertib (ON 01910.Na) hematological efects in patients with myelodysplastic syndrome and correlation with overall survival [ASH abstract 3822]. Blood. 2011;118;3822.
80. Yoshimi A, Goyama S, Watanabe-Okochi N, et al. Evi1 represses PTEN expression and activates PI3K/AKT/mTOR via interactions with polycomb proteins. Blood. 2011;117:3617-3628.
81. Janakiram M, Tirukonda VK, Sullivan M, Petrich AM. Emerging therapeutic targets in difuse large B-cell lymphoma. Curr Treat Options Oncol. 2012;13:82-101.
82. Zeidan AM, Gore SD, Komrokji RS. Higher-risk myelodysplastic syndromes with del(5q): is sequential azacitidine-lenalidomide combination the way to go? Expert Rev Hematol. 2013;6:251-254.
83. Sekeres MA, Tiu RV, Komrokji R, et al. Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes. Blood. 2012;120:4945-4951.
84. Soriano AO, Yang H, Faderl S, et al. Safety and clinical activity of the combination of 5-Azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood. 2007;110:2302-2308.
85. Quintas-Cardama A, Kanatarjian HM, Ravandi F et al. Very high rates of clinical and cytogenetic response with the combination of the histone deacetylase inhibitor pracinostat (SB939) and 5-Azacitidine in high-risk myelodysplastic syndrome [ASH abstract 3821]. Blood. 2012;119;3821.
86. Prebet TG, Gore S, Sun Z. Prolonged administration of azacitidine with or without entinostat increases rate of hematologic normalization for myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes: results of the US Leukemia Intergroup Trial E1905 [ASH abstract 601]. Blood. 2010;116:601.
87. Traina F, Visconte V, Elson P, Tabarroki A, Jankowska AM, Hasrouni E, et al. Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms. Leukemia. 2014;28:78-87.