Abstract
Higher-risk myelodysplastic syndromes (MDS) are aggressive disorders with rapid progression to AML and short survival. Azacitidine has shown unprecedented survival advantage in these patients but its treatment schedule involves daily hospital administrations for 7 days every 4 weeks. Due to patient and staffing constraints, we have treated 50 patients with a 5-day dose-intensified (500 mg/m2 total monthly dose divided in 5 days) azacitidine schedule in our center. The regimen was well tolerated, with Grade 3/4 adverse events seen in 24 % patients and only two discontinuations due to toxicity. The response rate was similar to that reported with the 7-day schedule: 16 % complete remissions, 32 % partial remissions, and 62 % transfusion independence. The median survival was 19.2 months from diagnosis. In addition, this regimen reduced hospital visits by 28 % and drug use by 30 %. Our results demonstrate the safety and efficacy of a dose-intensified 5-day regimen.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Reference
Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al (1997) International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079–2088
Alessandrino EP, la Porta MG, Bacigalupo A, Van Lint MT, Falda M, Onida F et al (2008) WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Blood 112:895–902
Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F et al (2012) Revised international prognostic scoring system for myelodysplastic syndromes. Blood 120:2454–2465
la Porta MG, Malcovati L, Strupp C, Ambaglio I, Kuendgen A, Zipperer E et al (2011) Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome. Haematologica 96:441–449
Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A et al (2009) 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 10:223–232
Santini V, Alessandrino PE, Angelucci E, Barosi G, Billio A, Di MM et al (2010) Clinical management of myelodysplastic syndromes: update of SIE, SIES, GITMO practice guidelines. Leuk Res 34:1576–1588
Lyons RM, Cosgriff TM, Modi SS, Gersh RH, Hainsworth JD, Cohn AL et al (2009) Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes. J Clin Oncol 27:1850–1856
Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937–951
Almeida AM, Pierdomenico F (2012) Generalized skin reactions in patients with MDS and CMML treated with azacitidine: effective management with concomitant prednisolone. Leuk Res 36:e211–e213
Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD et al (2006) Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 108:419–425
(2013) VIDAZA prescribing information. European Medicines Agency
Voso MT, Fianchi L, Criscuolo M, Greco M, D’Alo F, Hohaus S et al (2012) Azacitidine in a patient with myelodysplastic syndrome: impact of switching from a 5-day to the approved 7-day dosing schedule. Leuk Res 36:e15–e17
Itzykson R, Thépot S, Quesnel B, Dreyfus F, Recher C, Wattel E et al (2012) Long-term outcome of higher-risk MDS patients treated with azacitidine: an update of the GFM compassionate program cohort. Blood 119(25):6172–6173
Acknowledgments
The authors would like to thank Maria Gomes da Silva, Isabel Boaventura, and João Frade for their critical review of the manuscript.
Conflict of interest
Dr Almeida receives consulting fees from Celgene and Novartis and is on the board of speakers for Bristol–Meyer Squibb, Shire, and Amgen. Drs Pierdomenico and Esteves have no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Pierdomenico, F., Esteves, S. & Almeida, A. Efficacy and tolerability of 5-day azacytidine dose-intensified regimen in higher-risk MDS. Ann Hematol 92, 1201–1206 (2013). https://doi.org/10.1007/s00277-013-1762-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-013-1762-9