Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: Results from the nordic NMDSG08A phase II trial

Blood Cancer Journal

Volumn 4, Issue 3, 2014, Pages

  Tobiasson, M ^a   Dybedahl, I ^b   Holm, M S ^c   Karimi, M ^d   Brandefors, L ^e   Garelius, H ^f   Grovdal M ^g   Hogh Dufva I ^h   Gronbaek K ⁱ   Jansson, M ^d   Marcher, C ^j   Nilsson, L ^k   Kittang, A O ^l   Porwit, A ^a   Saft, L ^a   Mollgard L ^a   Hellstrom Lindberg E ^a  

^a KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^b OSLO UNIVERSITY HOSPITAL   (Norway)

^c AARHUS UNIVERSITY HOSPITAL   (Denmark)

^d KAROLINSKA INSTITUTE   (Sweden)

^e SUNDERBY HOSPITAL   (Sweden)

^f SAHLGRENSKA UNIVERSITY HOSPITAL   (Sweden)

^g STOCKHOLM SÖDER HOSPITAL   (Sweden)

^h GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

ⁱ Rigshospitalet   (Denmark)

^j ODENSE UNIVERSITY HOSPITAL   (Denmark)

^k LUND UNIVERSITY HOSPITAL   (Sweden)

^l UNIVERSITY OF BERGEN   (Norway)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ANTIANEMIC AGENT; AZACITIDINE; DNA METHYLTRANSFERASE 3A; ERYTHROPOIETIN; GRANULOCYTE COLONY STIMULATING FACTOR;

ADULT; AGED; ARTICLE; BLOOD TRANSFUSION; CHROMOSOME ABERRATION; CLINICAL ARTICLE; CONSTIPATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CYTOGENETICS; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG FEVER; DYSPNEA; ERYTHROCYTE TRANSFUSION; FAINTNESS; FEBRILE NEUTROPENIA; FEMALE; FOLLOW UP; GENE MUTATION; HEART ARRHYTHMIA; HEART ATRIUM FIBRILLATION; HEART VENTRICLE TACHYCARDIA; HUMAN; HUMAN CELL; INFECTION; INJECTION SITE REACTION; INTERMEDIATE RISK PATIENT; LOW RISK PATIENT; MALE; MONOTHERAPY; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MYELODYSPLASTIC SYNDROME; NEUTROPENIA; OUTCOME ASSESSMENT; PANCYTOPENIA; PHASE 2 CLINICAL TRIAL; PROSPECTIVE STUDY; REFRACTORY CYTOPENIA WITH MULTILINEAGE DYSPLASIA; SIDE EFFECT; SUDDEN DEATH; THORAX PAIN; THROMBOCYTE COUNT; THROMBOCYTOPENIA; TRANSFUSION INDEPENDENCE; TREATMENT RESPONSE; TRISOMY 21; TRISOMY 8; URETHRA OBSTRUCTION; VALVULAR HEART DISEASE; VERY ELDERLY;

EID: 84901839639     PISSN: None     EISSN: 20445385     Source Type: Journal    
DOI: 10.1038/bcj.2014.8     Document Type: Article

References (28)

1. Jadersten M, Montgomery SM, Dybedal I, Porwit-MacDonald A, Hellstrom-Lindberg E. Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood 2005; 106: 803-811.
2. 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. United States 2008; 111: 574-582.
3. Greenberg PL, Sun Z, Miller KB, Bennett JM, Tallman MS, Dewald G 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.
4. Kelaidi C, Park S, Sapena R, Beyne-Rauzy O, Coiteux V, Vey N et al. Long-term outcome of anemic lower-risk myelodysplastic syndromes without 5q deletion refractory to or relapsing after erythropoiesis-stimulating agents. Leukemia 2013; 27: 1283-1290.
5. Hellstrom-Lindberg E, Negrin R, Stein R, Krantz S, Lindberg G, Vardiman J 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 1997; 99: 344-351.
6. Jadersten M, Malcovati L, Dybedal I, Della Porta MG, Invernizzi R, Montgomery SM et al. Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol 2008; 26: 3607-3613.
7. Armand P, Kim HT, Cutler CS, Ho VT, Koreth J, Alyea EP et al. Prognostic impact of elevated pretransplantation serum ferritin in patients undergoing myeloablative stem cell transplantation. Blood 2007; 109: 4586-4588.
8. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A 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 2009; 10: 223-232.
9. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R 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.
10. Lyons RM, Cosgriff TM, Modi SS, Gersh RH, Hainsworth JD, Cohn AL et al. Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol 2009; 27: 1850-1856.
11. Musto P, Maurillo L, Spagnoli A, Gozzini A, Rivellini F, Lunghi M 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 2010; 116: 1485-1494.
12. Prébet T, Thepot S, Gore SD, Dreyfus F, Fenaux P, Vey N. Outcome of patients with low-risk myelodysplasia after azacitidine treatment failure. Haematologica 2013; 98: e18-e19.
13. Fili C, Malagola M, Follo MY, Finelli C, Iacobucci I, Martinelli G et al. Prospective phase II study on 5-days azacitidine (5d-AZA) for treatment of symptomatic and/or erythropoietin unresponsive patients with low/int-1 risk myelodysplastic patients. Clin Cancer Res 2013; 19: 3297-3308.
14. Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 2011; 364: 2496-2506.
15. Bejar R, Stevenson KE, Caughey BA, Abdel-Wahab O, Steensma DP, Galili N 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.
16. Itzykson R, Kosmider O, Cluzeau T, Mansat-De Mas V, Dreyfus F, Beyne-Rauzy O et al. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia 2011; 25: 1147-1152.
17. Bejar RSK, Stojanov P, Zaneveld JE, Bar-Natan M, Caughey B. Next-generation sequencing of 213 MDS patient samples identifies mutation profiles associated with response to hypomethylating agents and overall survival. Leuk Res 2013; 37: S19-S20(abstract O-024).
18. Möllgård L, Saft L, Treppendahl MB, Dybedal I, Nørgaard JM, Astermark J et al. Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities. Haematologica 2011, 2011-07-01 96: 963-971.
19. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 2009; 25: 2078-2079.
20. Wang K, Li M, Hakonarson H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 2010; 38: e164.
21. Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA et al. A map of human genome variation from population-scale sequencing. Nature 2010; 467: 1061-1073.
22. Tennessen JA, Bigham AW, O'Connor TD, Fu W, Kenny EE, Gravel S et al. Evolution and functional impact of rare coding variation from deep sequencing of human exomes. Science [Research Support, N.I.H., Extramural] 2012; 337: 64-69.
23. Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 2006; 108: 419-425.
24. Garcia-Manero G, Xiao L, Najla AA, Mishra A, Padron E, Lancet JE et al. Outcome of patients (pts) with low and intermediate-1 risk myelodysplastic syndrome (MDS) after hypomethylating agent (HMA) failure. Blood 2013; 122: 388.
25. Grovdal M, Khan R, Aggerholm A, Antunovic P, Astermark J, Bernell P et al. Negative effect of DNA hypermethylation on the outcome of intensive chemotherapy in older patients with high-risk myelodysplastic syndromes and acute myeloid leukemia following myelodysplastic syndrome. Clin Cancer Res 2007; 13: 7107-7112.
26. Mian SA, Smith AE, Kulasekararaj AG, Kizilors A, Mohamedali AM, Lea NC et al. Spliceosome mutations exhibit specific associations with epigenetic modifiers and proto-oncogenes mutated in myelodysplastic syndrome. Haematologica 2013; 98: 1058-1066.
27. Papaemmanuil E, Gerstung M, Malcovati L, Tauro S, Gundem G, Van Loo P et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood 2013; 122: 3616-3627.
28. Qu Y, Lennartsson A, Gaidzik VI, Deneberg S, Bengtzen S, Arzenani MK et al. Genome-Wide DNA Methylation Analysis Shows Enrichment of Differential Methylation in 'Open Seas' and Enhancers and Reveals Hypomethylation in DNMT3A Mutated Cytogenetically Normal AML (CN-AML), 16/11/2012. ASH meeting abstract, American Society of Hematology, 2012.