Scientific Online Resource System

Scripta Scientifica Medica

Outcome after azacitidine treatment in patients with high-risk myelodysplastic syndrome and acute myeloid leukemia in the Clinic of Hematology at St. Marina University Hospital, Varna

Ilina Micheva, Vladimir Gerov, Stela Dimitrova, Merlin Efraim, Liana Gercheva

Abstract

Introduction: Hypomethylating agents have become a standard therapy for high-risk myelodysplastic syndromes (MDS) and elderly patients with acute myeloid leukemia (AML).

Aim: The aim of the study was to assess the efficacy of azacitidine treatment in patients with MDS and AML followed for 18 months.

Materials and Methods: Twenty-seven patients with MDS and AML treated in the Clinic of Hematology at St. Marina University Hospital, Varna were included in the study. Azacitidine was administered subcutaneously in at a dose of 75 mg/m2 for 7 days. Disease assessment was performed on  the 3rd month, 6th month, and at progression.

Results: Twenty-seven patients were analyzed. Their median age was 71.5 years. Nine had refractory anemia with excess of blasts II (RAEB II), 5 had chronic myelomonocytic leukemia II (CMML II), 1 was with unclassifiable MDS (MDS-U), and 12 with AML. The median number of administered cycles was 6 (1-19). Eleven patients completed 6 cycles of azacitidine. Partial response was achieved in 9 patients (33%) (7 MDS and 2 AML), stable disease in 8 (29%) (5 MDS and 3 AML). Progressive disease was observed in 10 patients (37%). The response correlated with the type of the disease (p=0.03), cytogenetic risk (p=0.01), and survival (p=0.000). At 18 months, 60% of MDS patients were alive compared to 41.7% in the AML group. The median time to death in the AML patient group was 2.5 months. The mean overall survival was 10.4 months (12.6 months for MDS patients and 5.4 months for AML patients).

Conclusion: The therapy with azacitidine is an option for elderly patients with high-risk MDS.  In patients with AML a rapid progression is observed during the first two cycles with mortality rate of 58.3%.


Keywords

MDS, AML, Hypomethylating agents, Azacitidine

Full Text


References

Weber M, Hellmann I, Stadler MB, Ramos L, Pääbo S, Rebhan M, et al. Distribution, silencing potential and evo- lutionary impact of promoter DNA meth- ylation in the human genome. Nat Genet. 2007;39(4):457-66. doi: 10.1038/ng1990.

Esteller M. Epigenetics in cancer. N Engl J Med. 2008;358(11):1148-59. doi: 10.1056/NEJMra072067.

Figueroa ME, Skrabanek L, Li Y, Jiemjit A, Fandy TE, Paietta E, et al. MDS and secondary AML display unique patterns and abundance of aberrant DNA methylation. Blood. 2009;114(16):3448-58. doi: 10.1182/blood-2009-01-200519.

Aggerholm A, Holm MS, Guldberg P, Olesen LH, Hokland P. Promoter hypermethylation of p15INK4B, HIC1, CDH1, and ER is frequent in myelodysplastic syndrome and predicts poor prognosis in early-stage patients. Eur J Haematol. 2006;76(1):23-32. doi: 10.1111/j.1600-0609.2005.00559.x.

Santini V, Melnick A, Maciejewski JP, Duprez E, Nervi C, Cocco L, et al. Epigenetics in focus: pathogenesis of myelodysplastic syndromes and the role of hypomethylating agents. Crit Rev Oncol Hematol. 2013;88(2):231-45. doi: 10.1016/j.critrevonc.2013.06.004.

Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454-65. doi: 10.1182/blood-2012-03-420489.

Cheson BD, Greenberg P, 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(2):419-25. doi: 10.1182/blood-2005-10-4149.

Valent P, Horny HP, Bennett JM, Fonatsch C, Germing U, Greenberg P et al. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res. 2007; 31(6):727–36. doi: 10.1016/j.leukres.2006.11.009.

de Witte T, Suciu S, Verhoef G, Labar B, Archimbaud E, Aul C, 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. 2001;98(8):2326-31.

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(10):2429–40. doi: 10.1200/JCO.2002.04.117.

Fenaux P, Mufti GJ, Hellström-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(3):223-32. doi: 10.1016/S1470-2045(09)70003-8.

Visser O, Trama A, Maynadi´e M, Stiller C, Marcos-Gragera R, De Angelis R, et al. RARECARE Working Group. Incidence, survival and prevalence of myeloid malignancies in Europe. Eur J Cancer. 2012;48(17):3257-66. doi: 10.1016/j.ejca.2012.05.024.

Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126(3):291-9. doi: 10.1182/blood-2015-01-621664.




DOI: http://dx.doi.org/10.14748/ssm.v50i1.4349

Refbacks

About The Authors

Ilina Micheva
Medical University of Varna
Bulgaria

Clinic of Hematology, St. Marina University Hospital of Varna, 1 Hristo Smirnenski Str.,¨ 9010 Varna, Bulgaria

Vladimir Gerov
Medical University of Varna
Bulgaria

Clinic of Hematology, St. Marina University Hospital of Varna, 1 Hristo Smirnenski Str.,¨ 9010 Varna, Bulgaria

Stela Dimitrova
Medical University of Varna
Bulgaria

Clinic of Hematology, St. Marina University Hospital of Varna, 1 Hristo Smirnenski Str.,¨ 9010 Varna, Bulgaria

Merlin Efraim
Medical University of Varna
Bulgaria

Clinic of Hematology, St. Marina University Hospital of Varna, 1 Hristo Smirnenski Str.,¨ 9010 Varna, Bulgaria

Liana Gercheva
Medical University of Varna
Bulgaria

Clinic of Hematology, St. Marina University Hospital of Varna, 1 Hristo Smirnenski Str.,¨ 9010 Varna, Bulgaria

Font Size


|