Annals of Hematology

, Volume 94, Issue 12, pp 2003–2013 | Cite as

Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG)

  • Heiko Becker
  • Stefan Suciu
  • Björn Hans Rüter
  • Uwe Platzbecker
  • Aristoteles Giagounidis
  • Dominik Selleslag
  • Boris Labar
  • Ulrich Germing
  • Helmut R. Salih
  • Petra Muus
  • Karl-Heinz Pflüger
  • Anne Hagemeijer
  • Hans-Eckart Schaefer
  • Valeria Fiaccadori
  • Frédéric Baron
  • Arnold Ganser
  • Carlo Aul
  • Theo de Witte
  • Pierre W. Wijermans
  • Michael Lübbert
Original Article


In the European Organisation for Research and Treatment of Cancer (EORTC)/GMDSSG phase III trial 06011, we compared decitabine (15 mg/m2 every 8 h for 3 days) with best supportive care (BSC) in patients ≥60 years with myelodysplastic syndromes (MDS) by French-American-British (FAB) criteria. Here, we reinvestigate trial 06011 for the activity and efficacy specifically in patients with refractory anemia with excess blasts in transformation (RAEBt). Response rates in the decitabine arm (N = 40) were as follows: complete or partial remission, 15 %; hematologic improvement, 15 %; resistant disease, 30 %. RAEBt patients in the decitabine arm had longer progression-free survival (PFS; hazard ratio (HR) 0.30, 95 % confidence interval (CI) 0.18–0.51; median, 6.2 vs 2.8 months) and overall survival (OS; HR 0.68, 95 % CI 0.42–1.11; median, 8.0 vs 6.0 months) than in the BSC arm (N = 35). Censoring at allogeneic hematopoietic stem cell transplantation, the OS difference between the treatment groups increased, particularly among patients aged 60–74 years (HR 0.48, 95 % CI 0.26–0.89). After regrouping the study cohort according to World Health Organization (WHO) criteria, patients with acute myeloid leukemia (AML) (i.e., ≥20 % blasts) in the decitabine arm (N = 27) also had longer PFS than in the BSC arm (N = 23) (HR 0.46, 95 % CI 0.26–0.83; median, 6.2 vs 2.8 months). In conclusion, 3-day decitabine displays clinical activity and efficacy in MDS and/or AML with 5–30 % blood or 20–30 % marrow blasts.


RAEBt MDS AML Leukemia Allogeneic transplantation Epigenetic therapy 



We thank the following additional EORTC Headquarters staff who worked on this study: Christine de Balincourt, Edith Bastiaens, Caroline Gilotay, Ann Marinus, Liv Meert, Thomas Vandenberghe, and Christine Waterkeyn.


The study was supported by an educational grant from MGI Pharma and Johnson & Johnson. The publication was supported by the EORTC Cancer Research Fund.

Conflict of interest

Personal financial interests: none. Honoraria: U.P., Celgene, Novartis, Amgen; A.G., Celgene; D.S., Celgene, Novartis, Amgen; B.L., Novartis, MSD; U.G., MDS Register Düsseldorf, Johnson & Johnson; H.R.S., Celgene, Novartis; A.G., Genzyme. Funding: U.P., Celgene, Novartis; U.G., MDS Register Düsseldorf; A.G., Novartis. M.L., Janssen-Cilag, Celgene, Teva. Employment: B.H.R., Böhringer-Ingelheim. Patent rights: none. Consultancy Work: U.P., Celgene, Amgen, Novartis; A.G., Celgene; D.S., Celgene, Novartis, Amgen; H.R.S., Novartis, Amgen, BMS; and A.G., Celgene, Novartis.

Author contribution

Conception and design: H.B., S.S., A.Gi., P.M., A.Ga., C.A., T.d.W., and P.W.W.; provision of study materials or patients: B.H.R., U.P., A.Gi., D.S., B.L., U.G., H.R.S., P.M., K.-H.P., A.Ga., C.A., T.d.W., P.W.W., and M.L.; collection and assembly of data: S.S., B.H.R., U.P., A.Gi., D.S., U.G., P.M., K.-H.P., A.H., and M.L.; data analysis and interpretation: H.B., S.S., B.H.R., P.M., A.H., H.-E.S., V.F., F.B., T.d.W., P.W.W., and M.L.; drafting of the manuscript: H.B., S.S., and M.L.; and critical review and final approval of the manuscript: H.B., S.S., B.H.R., U.P., A.Gi., D.S., B.L., U.G., H.S., P.M., K.-H.P., A.H., H.-E.S., V.F., F.B., A.Ga., C.A., T.d.W., P.W.W., and M.L.

Supplementary material

277_2015_2489_MOESM1_ESM.pdf (582 kb)
ESM 1 (PDF 581 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Heiko Becker
    • 1
  • Stefan Suciu
    • 2
  • Björn Hans Rüter
    • 1
  • Uwe Platzbecker
    • 3
  • Aristoteles Giagounidis
    • 4
  • Dominik Selleslag
    • 5
  • Boris Labar
    • 6
  • Ulrich Germing
    • 7
  • Helmut R. Salih
    • 8
  • Petra Muus
    • 9
  • Karl-Heinz Pflüger
    • 10
  • Anne Hagemeijer
    • 11
  • Hans-Eckart Schaefer
    • 12
  • Valeria Fiaccadori
    • 2
  • Frédéric Baron
    • 13
  • Arnold Ganser
    • 14
  • Carlo Aul
    • 15
  • Theo de Witte
    • 9
  • Pierre W. Wijermans
    • 16
  • Michael Lübbert
    • 1
  1. 1.Department of Medicine IMedical Center-University of FreiburgFreiburgGermany
  2. 2.EORTC HeadquartersBrusselsBelgium
  3. 3.Department of Internal Medicine IUniversity Carl Gustav CarusDresdenGermany
  4. 4.Department of Hematology, Oncology and Palliative CareMarienhospital DüsseldorfDüsseldorfGermany
  5. 5.Department of HematologyAZ St-JanBruggeBelgium
  6. 6.University Hospital Center RebroZagrebCroatia
  7. 7.Department of Hematology, Oncology and Clinical ImmunologyUniversity Hospital DüsseldorfDüsseldorfGermany
  8. 8.Department of Hematology, Oncology and ImmunologyEberhard Karls UniversityTübingenGermany
  9. 9.Radboud University Medical CenterNijmegenNetherlands
  10. 10.Department of Medicine IIDIAKO BremenBremenGermany
  11. 11.Center for Human GeneticsUniversity of LeuvenLeuvenBelgium
  12. 12.Institute of PathologyUniversity of FreiburgFreiburgGermany
  13. 13.Centre Hospitalier Universitaire Sart-TilmanLiègeBelgium
  14. 14.Department of Hematology, Hemostasis, Oncology and Stem Cell TransplantationHannover Medical SchoolHannoverGermany
  15. 15.Department of Hematology and OncologySt. Johannes HospitalDuisburgGermany
  16. 16.Department of Internal MedicineHaga ZiekenhuisThe HagueNetherlands

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