Annals of Hematology

, Volume 89, Issue 4, pp 365–374 | Cite as

Patients with del(5q) MDS who fail to achieve sustained erythroid or cytogenetic remission after treatment with lenalidomide have an increased risk for clonal evolution and AML progression

  • Gudrun Göhring
  • Aristoteles Giagounidis
  • Guntram Büsche
  • Hans Heinrich Kreipe
  • Martin Zimmermann
  • Eva Hellström-Lindberg
  • Carlo Aul
  • Brigitte Schlegelberger
Original Article

Abstract

Lenalidomide consistently induces transfusion independence and complete cytogenetic response in patients with myelodysplastic syndromes with 5q deletion. Only limited information on long-term outcome is currently available. We performed a long-term follow-up analysis of 42 patients with low or intermediate risk myelodysplastic syndromes and 5q deletion treated with lenalidomide. At a median follow-up of 40 months, 58% of the patients achieved an erythroid response and 48% a cytogenetic response. Thirty-six percent of patients progressed into acute myeloid leukaemia. Most of them (87%) acquired chromosome aberrations in addition to the 5q deletion, i.e. underwent clonal evolution during leukaemogenesis. There were no clinical, cytological or cytogenetic markers at study entry that allowed prediction of increased risk of leukaemic transformation. However, erythroid and cytogenetic responders had a significantly decreased risk of progression to acute myeloid leukaemia (p = 0.001 and p = 0.009, respectively) compared to non-responders. Three and 5 years after study entry, the cumulative incidence of acute myeloid leukaemia for patients with a cytogenetic response was 10% and 21%, respectively, and for patients without cytogenetic response, it was 46% and 60%. Patients with del(5q) myelodysplastic syndromes without erythroid or cytogenetic remission after treatment with lenalidomide have a high risk for clonal evolution and acute myeloid leukaemia progression. In refractory, or relapsing, patients, genetic instability and clonal evolution seem to be the driving forces of leukaemic transformation. Regular follow-up investigations of del(5q) myelodysplastic syndrome patients treated with lenalidomide may help to identify patients requiring alternative treatment strategies.

Keywords

Myelodysplastic syndrome Acute myeloid leukaemia 5q deletion Clonal evolution Complex karyotype Leukaemia transformation Lenalidomide 

Notes

Acknowledgments

The authors would like to thank Lana Harder, Claudia Haferlach, Brigitte Mohr and Stefan Bohlander for providing cytogenetic data and Gillian Teicke for her help in preparing the manuscript. Finally, we thank Dr. Robert Knight, Celgene, for allowing us to use data obtained within the Celgene MDS-003 clinical trial.

Authorship and disclosures

GG, AG and BS were the principal investigators and take primary responsibility for the paper. AG and CA recruited the patients. GG, GB and HHK performed the laboratory work for this study. MZ participated in the statistical analysis. AG, EHL and BS co-ordinated the research. GG, AG and BS wrote the paper. The authors reported no potential conflicts of interest.

Funding

This study was supported by the BMBF (German Competence Network Acute and Chronic Leukaemias).

Supplementary material

277_2009_846_MOESM1_ESM.xls (42 kb)
Electronic supplementary material 1 Cytogenetic response under lenalidomide (XLS 42 kb)
277_2009_846_MOESM2_ESM.xls (29 kb)
Electronic supplementary material 2 Pre-treatment of patients with MDS and deletion in 5q before lenalidomide (XLS 29 kb)
277_2009_846_MOESM3_ESM.doc (74 kb)
Electronic supplementary material 3 Depicted are the cumulative incidences of acute myeloid leukaemia since study entry with lenalidomide therapy regarding neutropenia (a) and thrombocytopenia (b). (DOC 73.5 kb)
277_2009_846_MOESM4_ESM.jpg (434 kb)
Electronic supplementary material 4

Cytogenetic characteristics of the patients representing classical cytogenetics and FISH data (JPEG 434 kb).

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Gudrun Göhring
    • 1
  • Aristoteles Giagounidis
    • 2
  • Guntram Büsche
    • 3
  • Hans Heinrich Kreipe
    • 3
  • Martin Zimmermann
    • 4
  • Eva Hellström-Lindberg
    • 5
  • Carlo Aul
    • 2
  • Brigitte Schlegelberger
    • 1
  1. 1.Institute of Cell and Molecular PathologyHannover Medical SchoolHannoverGermany
  2. 2.Department of Haematology, Oncology and Clinical ImmunologySt. Johannes HospitalDuisburgGermany
  3. 3.Institute of PathologyHannover Medical SchoolHannoverGermany
  4. 4.Department of Paediatric Haematology/OncologyHannover Medical SchoolHannoverGermany
  5. 5.Division of Haematology and Centre of Experimental Haematology, Department of Medicine, Karolinska InstitutetKarolinska University HospitalStockholmSweden

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