The role of hypomethylating agents in myelodysplastic syndrome: Changing the management paradigm

Expert Review of Hematology

Volumn 6, Issue 6, 2013, Pages 665-676

  Merkel, Drorit G ^a   Nagler, Arnon ^a  

^a TEL AVIV UNIVERSITY   (Israel)

Author keywords

Decitabine; High risk; Hypomethylating agents; Int2; Myelodysplastic syndrome; Vidaza

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; ANTIHISTAMINIC AGENT; AZACITIDINE; BELINOSTAT; CORTICOSTEROID; CYTARABINE; DNA METHYLTRANSFERASE 3A; DNA METHYLTRANSFERASE INHIBITOR; ENTINOSTAT; GEMTUZUMAB OZOGAMICIN; HEMOGLOBIN; HISTONE DEACETYLASE INHIBITOR; LENALIDOMIDE; PANOBINOSTAT; PRIMROSE OIL; ROMIPLOSTIM; VALPROIC ACID; VORINOSTAT;

ABDOMINAL PAIN; ACUTE GRAFT VERSUS HOST DISEASE; ACUTE GRANULOCYTIC LEUKEMIA; ALLOGENEIC STEM CELL TRANSPLANTATION; ANEMIA; ANOREXIA; ARTHRALGIA; BLEEDING; BONE MARROW SUPPRESSION; CHRONIC MYELOMONOCYTIC LEUKEMIA; COMORBIDITY; CONSTIPATION; CORTICOSTEROID THERAPY; CPG ISLAND; CYTOGENETICS; CYTOPENIA; DIARRHEA; DIZZINESS; DNA METHYLATION; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; DYSPNEA; ECCHYMOSIS; ERYTHROCYTE TRANSFUSION; FATIGUE; FEBRILE NEUTROPENIA; FEVER; GENE MUTATION; GERIATRIC PATIENT; HEADACHE; HEMOGLOBIN BLOOD LEVEL; HIGH RISK PATIENT; HUMAN; INFECTION RATE; INJECTION SITE ERYTHEMA; INJECTION SITE PAIN; INJECTION SITE REACTION; INTERNATIONAL PROGNOSTIC SCORING SYSTEM; KARYOTYPE; LEUKOPENIA; MULTICENTER STUDY (TOPIC); MULTIPLE CYCLE TREATMENT; MYELODYSPLASTIC SYNDROME; NAUSEA AND VOMITING; NEUTROPENIA; OVERALL SURVIVAL; PETECHIA; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PNEUMONIA; PRIORITY JOURNAL; PROGNOSIS; PROGRESSION FREE SURVIVAL; PROMOTER REGION; PRURITUS; QUALITY OF LIFE; RASH; REDUCED INTENSITY CONDITIONING; RELAPSE; REMISSION; REVIEW; RHINOPHARYNGITIS; SALVAGE THERAPY; SKIN IRRITATION; THORAX PAIN; THROMBOCYTE TRANSFUSION; THROMBOCYTOPENIA; TREATMENT RESPONSE;

ANTIMETABOLITES, ANTINEOPLASTIC; AZACITIDINE; CLINICAL TRIALS AS TOPIC; DNA MODIFICATION METHYLASES; DRUG THERAPY, COMBINATION; HISTONE DEACETYLASE INHIBITORS; HUMANS; MYELODYSPLASTIC SYNDROMES; PROGNOSIS; STEM CELL TRANSPLANTATION;

EID: 84887919993     PISSN: 17474086     EISSN: 17474094     Source Type: Journal    
DOI: 10.1586/17474086.2013.854699     Document Type: Review

References (92)

1. Rollison De, Howlader N, Smith MT et al. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood 112(1), 45-52 (2008
2. 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(8), 2985-2990 (1998
3. Jiang Y, Dunbar A, Gondek LP et al. Aberrant DNA methylation is a dominant mechanism in MDS progression to AML. Blood 113(6), 1315-1325 (2009
4. Santini V, Kantarjian HM, Issa JP. Changes in DNA methylation in neoplasia: Pathophysiology and therapeutic implications. Ann. Intern. Med. 134(7), 573-586 (2001
5. Santini V. Azacitidine: Activity and efficacy as an epigenetic treatment of myelodysplastic syndromes. Expert Rev. Hematol. 2(2), 121-127 (2009
6. Chuang JC, Yoo CB, Kwan JM et al. Comparison of biological effects of non-nucleoside DNA methylation inhibitors versus 5-Aza-2'-deoxycytidine. Mol. Cancer Ther. 4(10), 1515-1520 (2005
7. Stresemann C, Brueckner B, Musch T, Stopper H, Lyko F. Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines. Cancer Res. 66(5), 2794-2800 (2006
8. Stresemann C, Bokelmann I, Mahlknecht U, Lyko F. Azacytidine causes complex DNA methylation responses in myeloid leukemia. Mol. Cancer Ther. 7(9), 2998-3005 (2008
9. 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. 20(10), 2429-2440 (2002
10. Fenaux P, Mufti Gj, Hellstrom-Lindberg E et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: A randomised, open-label, phase III study. Lancet Oncol. 10(3), 223-232 (2009
11. Lubbert M, Suciu S, Baila L et al. Low-dose decitabine versus best supportive care in elderly patients with intermediateor high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: Final 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. 29(15), 1987-1996 (2011
12. Kantarjian H, Issa JP, Rosenfeld CS et al. Decitabine improves patient outcomes in myelodysplastic syndromes: Results of a phase III randomized study. Cancer 106(8), 1794-1803 (2006
13. 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. 27(23), 3842-3848 (2009
14. Kornblith AB, Herndon JE 2nd, Silverman LR et al. Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: A Cancer and Leukemia Group B study. J. Clin. Oncol. 20(10), 2441-2452 (2002
15. 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(1), 52-57 (2007
16. Lyons RM, Cosgriff TM, Modi SS et al. Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J. Clin. Oncol. 27(11), 1850-1856 (2009
17. Martin MG, Walgren RA, Procknow E et al. A phase II study of 5-day intravenous azacitidine in patients with myelodysplastic syndromes. Am. J. Hematol. 84(9), 560-564 (2009
18. Silverman LR, Fenaux P, Mufti GJ et al. Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes. Cancer 117(12), 2697-2702 (2011
19. Nazha A, Kantarjian HM, Cortes JE et al. Outcome of patients with myelodysplastic syndrome (MDS) with bone marrow (BM) blasts between 10 to 30% treated with hypomethylating agents versus intensive chemotherapy. ASH Annu. Meeting Abstr. 120(21), 4928 (2012
20. Pierdomenico F, Esteves S, Almeida A. Efficacy and tolerability of 5-day azacytidine dose-intensified regimen in higher-risk MDS. Ann. Hematol. 92(9), 1201-1206 (2013
21. Iastrebner M, Jang JH, Nucifora E et al. Decitabine in myelodysplastic syndromes and chronic myelomonocytic leukemia: Argentinian/South Korean multi-institutional clinical experience. Leuk. Lymphoma 51(12), 2250-2257 (2010
22. Lee JH, Jang JH, Park J et al A prospective multicenter observational study of decitabine treatment in Korean patients with myelodysplastic syndrome Haematologica 96(10), 1441-1447 (2011
23. van der Helm LH, Alhan C, Wijermans PW et al. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme. Br. J. Haematol. 155(5), 599-606 (2011
24. Duong VH, Lancet JE, Alrawi E et al. Outcome of azacitidine treatment in patients with therapy-related myeloid neoplasms with assessment of prognostic risk stratification models. Leuk. Res. 37(5), 510-515 (2013
25. Fianchi L, Criscuolo M, Lunghi M et al Outcome of therapy-related myeloid neoplasms treated with azacitidine. 5, 44 (2012)Leuk Res; 37(5):510-5 (2013
26. Uchida T, Ogawa Y, Kobayashi Y et al. Phase I and II study of azacitidine in Japanese patients with myelodysplastic syndromes. Cancer Sci. 102(9), 1681 (2011
27. Oki Y, Kondo Y, Yamamoto K et al. Phase I/II study of decitabine in patients with myelodysplastic syndrome: A multi-center study in Japan. Cancer Sci. 103(10), 1839-1847 (2012
28. Borthakur G, Ahdab SE, Ravandi F et al. Activity of decitabine in patients with myelodysplastic syndrome previously treated with azacitidine. Leuk. Lymphoma 49(4), 690-695 (2008
29. Bhatnagar B, Zandberg DP, Vannorsdall EJ et al. Lack of response of Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) to decitabine after failure of azacitidine. ASH Annu. Meeting Abstr. 120(21), 3858 (2012
30. Garcia-Manero G, Gore SD, Cogle C et al. Phase I study of oral azacitidine in myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J. Clin. Oncol. 29(18), 2521-2527 (2011
31. Garcia-Manero G, Gore SD, Kambhampati S et al. Safety and efficacy of oral azacitidine (CC-486) administered in extended treatment schedules to patients with lower-risk myelodysplastic syndromes. ASH Annu. Meeting Abstr. 120(21), 424 (2012
32. Stauder R. The challenge of individualised risk assessment and therapy planning in elderly high-risk myelodysplastic syndromes (MDS) patients. Ann. Hematol. 91(9), 1333-1343 (2012
33. Seymour JF, Fenaux P, Silverman LR et al. Effects of azacitidine compared with conventional care regimens in elderly (‡ 75 years) patients with higher-risk myelodysplastic syndromes. Crit. Rev. Oncol. Hematol. 76(3), 218-227 (2010
34. Itzykson R, Thepot S, Quesnel B et al. Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood 117(2), 403-411 (2011
35. 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(5), 956-962 (2000
36. Qin T, Castoro R, El Ahdab S et al. Mechanisms of resistance to decitabine in the myelodysplastic syndrome. PLoS ONE 6(8), e23372 (2011
37. Delhommeau F, Dupont S, Della Valle V et al. Mutation in TET2 in myeloid cancers. N. Engl. J. Med. 360(22), 2289-2301 (2009
38. Itzykson R, Kosmider O, Cluzeau T et al. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia 25(7), 1147-1152 (2011
39. Link PA, Baer MR, James SR, Jones DA, Karpf AR. p53-inducible ribonucleotide reductase (p53R2/RRM2B) is a DNA hypomethylation-independent decitabine gene target that correlates with clinical response in myelodysplastic syndrome/acute myelogenous leukemia. Cancer Res. 68(22), 9358-9366 (2008
40. Voso Mt, Fabiani E, Piciocchi A et al. Role of BCL2L10 methylation and TET2 mutations in higher risk myelodysplastic syndromes treated with 5-Azacytidine. Leukemia 25(12), 1910-1913 (2011
41. Jabbour E, Garcia-Manero G, Ravandi F et al. Prognostic factors associated with disease progression and overall survival in patients with myelodysplastic syndromes treated with decitabine. Clin. Lymphoma Myeloma Leuk. 13(2), 131-138 (2013
42. Fenaux P, Bowen D, Gattermann N et al. Practical use of azacitidine in higher-risk myelodysplastic syndromes: An expert panel opinion. Leuk. Res. 34(11), 1410-1416 (2010
43. Platzbecker U, Aul C, Ehninger G, Giagounidis A. Reduction of 5-Azacitidine induced skin reactions in MDS patients with evening primrose oil. Ann. Hematol. 89(4), 427-428 (2010
44. Santini V, Fenaux P, Mufti GJ et al. Management and supportive care measures for adverse events in patients with myelodysplastic syndromes treated with azacitidine. Eur. J. Haematol. 85(2), 130-138 (2010
45. Itzykson R, Thepot 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. 36(4), 397-400 (2012
46. Martinez-Frances A. Adverse effects of azacitidine: Onset, duration, and treatment. Adv. Ther. 28(Suppl. 4), 1-5 (2010
47. Toma A, Fenaux P, Dreyfus F, Cordonnier C. Infections in myelodysplastic syndromes. Haematologica 97(10), 1459-1470 (2012
48. Fenaux P, Gattermann N, Seymour JF et al. Prolonged survival with improved tolerability in higher-risk myelodysplastic syndromes: Azacitidine compared with low dose ara-C. Br. J. Haematol. 149(2), 244-249 (2010
49. Merkel D, Filanovsky K, Gafter-Gvili A et al. Predicting infections in high-risk patients with myelodysplastic syndrome/ acute myeloid leukemia treated with azacitidine: A retrospective multicenter study. Am. J. Hematol. 88(2), 130-134 (2013
50. Greenberg PL, Garcia-Manero G, Moore M et al. A randomized controlled trial of romiplostim in patients with low-or intermediate-risk myelodysplastic syndrome receiving decitabine. Leuk. Lymphoma 54(2), 321-328 (2013
51. Douvali E, Papoutselis M, Spanoudakis E et al. Safety and efficacy of azacitidine in Myelodysplastic Syndrome (MDS) patients with mild and moderate renal impairment. Presented at: ASH Annual Meeting Abstracts 120(21), 1716 (2012
52. Batty GN, Kantarjian H, Issa JP et al. Feasibility of therapy with hypomethylating agents in patients with renal insufficiency. Clin. Lymphoma Myeloma Leuk. 10(3), 205-210 (2010
53. Musto P, Maurillo L, Spagnoli A et al. Azacitidine for the treatment of lower risk myelodysplastic syndromes: A retrospective study of 74 patients enrolled in an Italian named patient program. Cancer 116(6), 1485-1494 (2010
54. Fili C, Malagola M, Follo MY et al. Prospective Phase II Study on 5-days Azactidine (5d-AZA) for treatment of symptomatic and/or erythropoetin unresponsive patients with Low/INT-1 risk myelodysplastic syndromes Clin Cancer Res doi:10.1158/1078-0432.CCR-12-3540 (2013) (Epub ahead of print
55. Sayar H, Chan RJ, Orschell CM et al. Thrice weekly azacitidine does not improve hematological responses in lower-risk myelodysplastic syndromes: A study of the Hoosier Oncology Group. Leuk. Res. 35(8), 1108-1110 (2011
56. Mishra A, Lancet JE, Ali NHA et al. Outcome of Patients with Lower-Risk Myelodysplastic Syndrome (MDS) After Azacitidine (AZA) Treatment Failure. Presented at: ASH Annual Meeting Abstracts 120(21), 2815 (2012
57. Komrokji RS, Bally C, Itzykson R et al Azacitidine Treatment for Lenalidomide (LEN)-Resistant Myelodysplastic Syndrome (MDS) with Del 5q. Presented at: ASH Annual Meeting Abstracts 120(21), 3833 (2012
58. Jabbour E, Mathisen MS, Garcia-Manero G et al. Allogeneic hematopoietic stem cell transplantation versus hypomethylating agents in patients with myelodysplastic syndrome: A retrospective case-control study. Am. J. Hematol. 88(3), 198-200 (2011
59. Platzbecker U, Schetelig J, Finke J et al. Allogeneic hematopoietic cell transplantation in patients' age 60-70 years with de novo high-risk myelodysplastic syndrome or secondary acute myelogenous leukemia: Comparison with patients lacking donors who received azacitidine. Biol. Blood Marrow Transplant. 18(9), 1415-1421 (2012
60. Engel NR, Rank A. Epigenomics in hematopoietic transplantation: Novel treatment strategies. Epigenomics 3(5), 611-623 (2011
61. Kim DY, Lee JH, Park YH et al. Feasibility of hypomethylating agents followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome. Bone Marrow Transplant. 47(3), 374-379 (2012
62. Steensma DP. Tuning the rigging before sailing off into the stormy sea of stem cell transplants for patients with myelodysplastic syndromes. Biol. Blood Marrow Transplant. 18(8), 1145-1147(2012
63. De Padua Silva L, De Lima M, Kantarjian H et al. Feasibility of allo-SCT after hypomethylating therapy with decitabine for myelodysplastic syndrome. Bone Marrow Transplant. 43(11), 839-843 (2009
64. Field T, Perkins J, Huang Y et al. 5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 45(2), 255-260 (2010
65. Greenberg Pl, Attar E, Bennett JM et al. NCCN Clinical Practice Guidelines in Oncology: Myelodysplastic syndromes. J. Natl Compr. Canc. Netw. 9(1), 30-56 (2011
66. Lubbert M, Bertz H, Ruter B et al. Non-intensive treatment with low-dose 5-Aza-2'-deoxycytidine (DAC) prior to allogeneic blood SCT of older MDS/AML patients. Bone Marrow Transplant. 44(9), 585-588 (2009
67. Cogle CR, Imanirad I, Wiggins LE et al. Hypomethylating agent induction therapy followed by hematopoietic cell transplantation is feasible in patients with myelodysplastic syndromes. Clin. Adv. Hematol. Oncol. 8(1), 40-46 (2010
68. Gerds AT, Gooley TA, Estey EH, Appelbaum FR, Deeg HJ, Scott BL. Pretransplantation therapy with azacitidine vs induction chemotherapy and posttransplantation outcome in patients with MDS. Biol. Blood Marrow Transplant. 18(8), 1211-1218 (2012
69. Damaj G, Duhamel A, Robin M et al. Impact of azacitidine before allogeneic stem-cell transplantation for myelodysplastic syndromes: A study by the Societe Francaise de Greffe de Moelle et de Therapie-Cellulaire and the Groupe-Francophone des Myelodysplasies. J. Clin. Oncol. 30(36), 4533-4540 (2012
70. Jabbour E, Giralt S, Kantarjian H et al. Low-dose azacitidine after allogeneic stem cell transplantation for acute leukemia. Cancer 115(9), 1899-1905 (2009
71. De Lima M, Giralt S, Thall PF et al. Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: A dose and schedule finding study. Cancer 116(23), 5420-5431 (2010
72. Bolanos-Meade J, Smith BD, Gore SD et al. 5-Azacytidine as salvage treatment in relapsed myeloid tumors after allogeneic bone marrow transplantation. Biol. Blood Marrow Transplant. 17(5), 754-758 (2011
73. Platzbecker U, Wermke M, Radke J et al. Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: Results of the RELAZA trial. Leukemia 26(3), 381-389 (2012
74. Czibere A, Bruns I, Kroger N et al. 5-Azacytidine for the treatment of patients with acute myeloid leukemia or myelodysplastic syndrome who relapse after allo-SCT: A retrospective analysis. Bone Marrow Transplant. 45(5), 872-876 (2010
75. Schroeder T, Czibere A, Platzbecker U et al. Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation. Leukemia 27(6), 1229-1235 (2013
76. Kim SY, Cho SG, Cho BS et al. Azacytidine treatment after discontinuation of immunosuppressants in patients with myelodysplastic syndrome and relapse after allo-SCT at a single center. Bone Marrow Transplant. 45(8), 1375-1376 (2010
77. Lal G, Zhang N, Van Der Touw W et al. Epigenetic regulation of Foxp3 expression in regulatory T cells by DNA methylation. J. Immunol. 182(1), 259-273 (2009
78. Goodyear OC, Dennis M, Jilani NY et al. Azacitidine augments expansion of regulatory T cells after allogeneic stem cell transplantation in patients with acute myeloid leukemia (AML). Blood 119(14), 3361-3369 (2012
79. Gore SD, Baylin S, Sugar E et al. Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms. Cancer Res. 66(12), 6361-6369 (2006
80. Blum W, Klisovic RB, Hackanson B et al. Phase I study of decitabine alone or in combination with valproic acid in acute myeloid leukemia. J. Clin. Oncol. 25(25), 3884-3891 (2007
81. Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez B et al. Phase 1/2 study of the combination of 5-Aza-2'-deoxycytidine with valproic acid in patients with leukemia. Blood 108(10), 3271-3279 (2006
82. 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 110 (7), 2302-2308 (2007
83. Kuendgen A, Bug G, Ottmann OG et al. Treatment of poor-risk myelodysplastic syndromes and acute myeloid leukemia with a combination of 5-Azacytidine and valproic acid. Clin. Epigenet. 2, 389-399 (2011
84. Fandy TE, Herman JG, Kerns P et al. Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-Azacytidine and entinostat in patients with myeloid malignancies. Blood 114(13), 2764-2773 (2009
85. Nand S, Godwin J, Smith S et al. Hydroxyurea, azacitidine and gemtuzumab ozogamicin therapy in patients with previously untreated non-M3 acute myeloid leukemia and high-risk myelodysplastic syndromes in the elderly: Results from a pilot trial. Leuk. Lymphoma 49(11), 2141-2147 (2008
86. Bayraktar UD, Domingo GC, Schmit J, Pereira D. Azacitidine combined with gemtuzumab ozogamicin in patients with relapsed/refractory acute myeloid leukemia. Leuk. Lymphoma 52(5), 913-915 (2011
87. Sekeres MA, List AF, Cuthbertson D et al. Phase I combination trial of lenalidomide and azacitidine in patients with higher-risk myelodysplastic syndromes. J. Clin. Oncol. 28(13), 2253-2258 (2008
88. Sekeres MA, O'Keefe C, List AF et al. Demonstration of additional benefit in adding lenalidomide to azacitidine in patients with higher-risk myelodysplastic syndromes. Am. J. Hematol. 86(1), 102-103 (2008
89. Platzbecker U, Braulke F, Kündgen A et al.; German MDS Study Group. Seuqnetial combination of azacytidine and lenalidomide in del (5q) higher-risk myelodysplastic syndromes or acute myeloid leukemia: A phase I study. Leukemia 27, 1403-1407 (2013
90. Silverman LR. Hypomethylating agents in myelodysplastic syndromes changing the inevitable: The value of azacitidine as maintenance therapy, effects on transfusion and combination with other agents. Leuk. Res. 33(Suppl. 2), S18-21 (2009
91. Itzykson R, Fenaux P. Optimizing hypomethylating agents in myelodysplastic syndromes. Curr. Opin. Hematol. 19(2), 65-70 (2012
92. Ornstein MC, Sekeres MA. Combination strategies in myelodysplastic syndromes. Int. J. Hematol. 95(1), 26-33 (2012