Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Myelodysplasias

Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): A multicenter study

Leukemia volume 26, pages 1286–1292 (2012)Cite this article

Subjects

Abstract

Myelodysplastic syndromes (MDS) with del(5q) are considered to have a benign course of the disease. In order to address the issue of the propensity of those patients to progress to acute myeloid leukemia (AML), data on 381 untreated patients with MDS and del(5q) characterized by low or intermediate I International Prognostic Scoring System (IPSS) risk score were collected from nine centers and registries. Median survival of the entire group was 74 months. Transfusion-dependent patients had a median survival of 44 months vs 97 months for transfusion-independent patients (P<0.0001). Transfusion need at diagnosis was the most important patient characteristic for survival. Of the 381 patients, 48 (12.6%) progressed to AML. The cumulative progression rate calculated using the Kaplan–Meier method was 4.9% at 2 years and 17.6% at 5 years. Factors associated with the risk of AML transformation were high-risk World Health Organization adapted Prognostic Scoring System (WPSS) score, marrow blast count >5% and red-cell transfusion dependency at diagnosis. In conclusion, patients with MDS and del(5q) are facing a considerable risk of AML transformation. More detailed cytogenetic and molecular studies may help to identify the patients at risk of progression.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Van den Berghe JH, Cassima JJ, David G, Fryns JP, Michaux JL, Sokal G . Distinct haematological disorder with deletion of long arm of no.5 chromosom. Nature 1974; 251: 437–443.

    Article  CAS  PubMed  Google Scholar 

  2. Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House, Virginia, November 1997. J Clin Oncol 1999; 17: 3835–3849.

    Article  CAS  PubMed  Google Scholar 

  3. Brunning R, Orazi A, Germing U, Le Beau MM, Porwit A, Baumann I et al. Myelodysplastic syndromes/neoplasms. In Swerdlow S, et al (eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press: Lyon, 2008.

    Google Scholar 

  4. Giagounidis A, Germing U, Wainscoat JS, Boultwood J, Aul C . The 5q- Syndrome. Hematology 2004; 9: 271–277.

    Article  CAS  PubMed  Google Scholar 

  5. Germing U, Gattermann N, Strupp C, Aivado M, Aul C . Validation of the WHO proposals for a new classification of primary myelodysplastic syndromes: a retrospective analysis of 1600 patients. Leuk Res 2000; 24: 983–992.

    Article  CAS  PubMed  Google Scholar 

  6. Germing U, Strupp C, Kuendgen A, Isa S, Knipp S, Hildebrandt B et al. Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes. Haematologica 2006; 91: 1596–1604.

    PubMed  Google Scholar 

  7. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–2088.

    CAS  PubMed  Google Scholar 

  8. Malcovati L, Germing U, Kuendgen A, Della Porta MG, Pascutto C, Invernizzi R et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 2007; 25: 3503–3510.

    Article  PubMed  Google Scholar 

  9. Germing U, Aul C, Niemeyer CM, Haas R, Bennett JM . Epidemiology, classification and prognosis of adults and children with myelodysplastic syndromes. Ann Hematol 2008; 87: 691–699.

    Article  PubMed  Google Scholar 

  10. Kaplan EL, Meier P . Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457–481.

    Article  Google Scholar 

  11. Gooley TA, Leisenring W, Crowley J, Storer BE . Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999; 18: 695–706.

    Article  CAS  PubMed  Google Scholar 

  12. Gray RJ . A class of k-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16: 1141–1154.

    Article  Google Scholar 

  13. Cox DR . Regression models and life-tables. J Roy Stat Soc B 1972; 34: 187–220.

    Google Scholar 

  14. Pereira A, Nomdedeu M, Aguilar JL, Belkaid M, Carrio A, Cobo F et al. Transfusion intensity, not the cumulative red blood cell transfusion burden, determines the prognosis of patients with myelodysplastic syndrome on chronic transfusion support. Am J Hematol 2010; 86: 245–250.

    Article  Google Scholar 

  15. Patnaik MM, Lasho TL, Finke CM, Gangat N, Caramazza D, Holtan SG et al. WHO-defined ‘myelodysplastic syndrome with isolated del(5q)’ in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations. Leukemia 2010; 24: 1283–1289.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Mallo M, Cervera J, Schanz J, Such E, García-Manero G, Luño E et al. Impact of adjunct cytogenetic abnormalities for prognostic stratification in patients with myelodysplastic syndrome and deletion 5q. Leukemia 2011; 25: 110–120.

    Article  CAS  PubMed  Google Scholar 

  17. Haase D, Germing U, Schanz J, Pfeilstöcker M, Nösslinger T, Hildebrandt B et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood 2007; 110: 4385–4395.

    Article  CAS  PubMed  Google Scholar 

  18. Evers C, Beier M, Poelitz A, Hildebrandt B, Servan K, Drechsler M et al. Molecular definition of chromosome arm 5q deletion end points and detection of hidden aberrations in patients with myelodysplastic syndromes and isolated del(5q) using oligonucleotide array CGH. Genes Chromosomes Cancer 2007; 46: 1119–1128.

    Article  CAS  PubMed  Google Scholar 

  19. Thiel A, Beier M, Ingenhag D, Servan K, Hein M, Moeller V et al. Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance. Leukemia 2011; 25: 387–399.

    Article  CAS  PubMed  Google Scholar 

  20. Boultwood J, Pellagati A, McKenzie AN, Wainscout JS . Advances in the 5q-syndrome. Blood 2010; 116: 5803–5811.

    Article  CAS  PubMed  Google Scholar 

  21. Crescenzi B, La Starza R, Romoli S, Beacci D, Matteucci C, Barba G et al. Submicroscopic deletions in 5q- associated malignancies. Haematologica 2004; 89: 281–285.

    CAS  PubMed  Google Scholar 

  22. Pellagatti A, Marafioti T, Paterson JC, Barlow JL, Drynan LF, Giagounidis A et al. Induction of p53 and up-regulation of the p53 pathway in the human 5q- syndrome. Blood 2010; 115: 2721–2723.

    Article  CAS  PubMed  Google Scholar 

  23. Fidler C, Watkins F, Bowen DT, Littlewood TJ, Wainscoat JS, Boultwood J . NRAS, FLT3 and TP53 mutations in patients with myelodysplastic syndrome and a del(5q). Haematologica 2004; 89: 865–866.

    CAS  PubMed  Google Scholar 

  24. Jadersten M, Saft L, Pellagatti A, Göhring G, Wainscoat JS, Boultwood J et al. Clonal heterogeneity in the 5q-syndrome: p53 expressing progenitors prevail during lenalidomide treatment and expand at disease progression. Haematologica 2009; 94: 1762–1766.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Ades L, Lebras F, Sebert M, Kelaidi C, Lamy T, Dreyfus F et al. Treatment with Lenalidomide does not appear to increase the risk of leukemia progression in lower risk myelodysplastic syndrome with 5q deletion. A comparative analysis by the GFM. Haematologica 2011, (in press).

  26. Gohring G, Giagounidis A, Busche G, Kreipe HH, Zimmermann M, Hellstrom-Lindberg E et al. 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. Ann Hematol 2010; 89: 365–374.

    Article  PubMed  Google Scholar 

  27. Neukirchen J, Blum S, Kuendgen A, Strupp C, Aivado M, Haas R et al. Platelet counts and haemorrhagic diathesis in patients with myelodysplastic syndromes. Eur J Haematol 2009; 83: 477–482.

    Article  PubMed  Google Scholar 

  28. Matsuda A, Germing U, Jinnai I, Misumi M, Kuendgen A, Knipp S et al Difference in clinical features between Japanese and German patients with refractory anemia in myelodysplastic syndromes. Blood 2005; 106: 2633–2640.

    Article  CAS  PubMed  Google Scholar 

  29. Wang H, Wang X, Xu X, Lin G . Cytogenetic features and prognosis analysis in Chinese patients with myelodysplastic syndrome: a multicenter study. Ann Hematol 2010; 89: 535–544.

    Article  PubMed  Google Scholar 

  30. Jung SW, Lee SY, Jekarl DW, Kim M, Lim J, Kim Y et al. Cytogenetic characteristics and prognosis analysis in 231 myelodysplastic syndrome patients from a single institution. Leuk Res 2011; 35: 735–740.

    Article  PubMed  Google Scholar 

  31. Lee HR, Oh B, Hong DS, Zang DY, Yoon HJ, Kim HJ et al. Cytogenetic features of 5q deletion and 5q- syndrome in myelodysplastic syndrome in Korea; marker chromosomes proved to be chromosome 5 with interstitial deletion by fluorescence in situ hybridization. Cancer Genet Cytogenet 2010; 203: 193–202.

    Article  CAS  PubMed  Google Scholar 

  32. List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. New Engl J Med 2006; 355: 1456–1465.

    Article  CAS  PubMed  Google Scholar 

  33. Fenaux P, Giagounidis A, Selleslag D, Beyne-Rauzy O, Mufti G, Mittelman M et al. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q. Blood 2011; 118: 3765–3776.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by Celgene.

Author information

Authors and Affiliations

  1. Department of Hematology, Oncology and Clinical Immunology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

    U Germing, A Kündgen & R Haas

  2. Institute for Medical Information Sc,

    M Lauseker & J Hasford

  3. i,

    M Lauseker & J Hasford

  4. ences, Biometry, and Epidemiology, Ludwig-Maximilians-University of Munich, Munich, Germany

    M Lauseker & J Hasford

  5. Institute for Human Genetics, Heinrich-Heine-University Düsse,

    B Hildebrandt

  6. l,

    B Hildebrandt

  7. dorf, Düsseldorf, Germany

    B Hildebrandt

  8. Hematology division, Department of Internal Medicine, University Hospital, Patras, Greece

    A Symeonidis

  9. Institute of Hematology and Blood Transfusion, Prague, Czech Republic

    J Cermak

  10. Groupe Francophone des Myélodysplasies, Hôpital Avicenne, Bob, i, gny, France

    P Fenaux & C Kelaidi

  11. 3. Med. Abteilung und L.-Boltzmann-Inst. f. Leukämi,

    M Pfeilstöcker & T Nösslinger

  12. e,

    M Pfeilstöcker & T Nösslinger

  13. forschung & Hämatologie, Hanusch Krankenhaus, Wien, Austria

    M Pfeilstöcker & T Nösslinger

  14. Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Taussig Cancer Institute, Clev, e, land, OH, USA

    M Sekeres & J Maciejewski

  15. Department of Hematology and Oncology, Georg-August-University Göttingen, Göttingen, Germany

    D Haase & J Schanz

  16. Department of Haematology, The Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia

    J Seymour & M Kenealy

  17. Praxisklinik für Hämatologie und Onkologie, Koblenz, Germany

    R Weide

  18. Department of Hematology and Oncology, Albert-Ludwigs University Freiburg, Freiburg, Germany

    M Lübbert

  19. Department of Hematology and Oncology, University ‘Carl Gustav Carus’, Dresden, Germany

    U Platzbecker

  20. Department Internal Medicine I, Div. Haematol & Hemostaseol, Medical University of Vienna, Vienna, Austria

    P Valent

  21. Department Internal Med. III, Div. of Hematology and Oncology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany

    K Götze

  22. Department Internal Med V, Haem,

    R Stauder

  23. a,

    R Stauder

  24. tology and Oncology, Medical University Innsbruck, Innsbruck, Austria

    R Stauder

  25. Serv. Haematology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

    S Blum

  26. Department Internal Med I, University C,

    K-A Kreuzer

  27. o,

    K-A Kreuzer

  28. logne, Cologne, Germany

    K-A Kreuzer

  29. Department Internal Med III, University Ulm, Ulm, Germany

    R Schlenk

  30. Department Hematology, Hemostasis, Oncology & Stem Cell Transplantation, Medical School, Hannover, Germany

    A Ganser

  31. Department Internal Med III, Haematology and Internal Oncology, University Mannheim, Mannheim, Germany

    W-K Hofmann

  32. Department of Hematology, Oncology and Clinical Immunology, St Johannes Hospital Dui,

    C Aul & A Giagounidis

  33. s,

    C Aul & A Giagounidis

  34. burg, Duisburg, Germany

    C Aul & A Giagounidis

  35. Department of Haematology with Stem Cell Transplantation, Hemost,

    O Krieger

  36. a,

    O Krieger

  37. selogy and internal Oncology, Hospital Elisab,

    O Krieger

  38. e,

    O Krieger

  39. thinen, Linz, Austria

    O Krieger

Authors
  1. U Germing
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Lauseker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B Hildebrandt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Symeonidis
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J Cermak
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P Fenaux
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C Kelaidi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M Pfeilstöcker
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. T Nösslinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M Sekeres
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. J Maciejewski
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. D Haase
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. J Schanz
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. J Seymour
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. M Kenealy
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. R Weide
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. M Lübbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. U Platzbecker
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. P Valent
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. K Götze
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. R Stauder
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. S Blum
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. K-A Kreuzer
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. R Schlenk
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. A Ganser
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. W-K Hofmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. C Aul
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. O Krieger
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. A Kündgen
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. R Haas
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. J Hasford
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. A Giagounidis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to U Germing.

Ethics declarations

Competing interests

U Germing, P Fenaux, J Maciejewski, D Haase, U Platzbecker, KA Kreuzer and A Giagounidis are on the advisory board as well as have received research funding from Celgene. M Pfeilstöcker, T Nösslinger, M Sekeres, J Seymour, P Valent and A Kündgen are on the advisory board of Celgene. M Kenealy and R Weide have received research funding from Celgene.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Germing, U., Lauseker, M., Hildebrandt, B. et al. Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): A multicenter study. Leukemia 26, 1286–1292 (2012). https://doi.org/10.1038/leu.2011.391

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2011.391

Keywords

This article is cited by

Search

Advanced search

Quick links