Skip to main content
Log in

Does cytogenetic evolution have any prognostic relevance in myelodysplastic syndromes? A study on 153 patients from a single institution

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

The present study was designed to establish the incidence of cytogenetic evolution (CE), defined as the acquisition of chromosomal defects during the course of MDS, in order to correlate it with the WHO classification and IPSS score, and to assess its impact on overall survival (OS) and risk of MDS/AML evolution (progression-free interval, PFI) by means of Cox models for time-dependent covariates. Adjustments for known risk factors were achieved by performing a bivariable analysis. The study was carried out in 153 MDS patients who were followed for a median period of 45.2 months. Disease progression occurred in 42.4% of patients after a 65.2-month median PFI, while CE occurred in 30.7% of patients. Our study shows that (1) CE was more common in advanced than in early MDS, and advanced MDS presented secondary chromosomal defects distinct from those of early MDS; (2) CE significantly affected OS and PFI independently of other prognostic variables; (3) del(7)(q31q34) was the only secondary chromosomal defect which significantly affected PFI; trisomy 8 had only a moderate influence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Heaney ML, Golde DW (1999) Myelodysplasia. N Engl J Med 340:1649–1660

    Article  CAS  PubMed  Google Scholar 

  2. Nimer SD (2008) Myelodysplastic syndromes. Blood 11:4841–4851

    Article  Google Scholar 

  3. Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) (2008) Tumours of haematopoietic and lymphoid tissues. World health organization classification of tumours. IARC, Lyon

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Nösslinger T, Reisner R, Koller E, Grüner H, Tüchler H, Nowotny H et al (2001) Myelodysplastic syndromes, from the French-American-British to world health organization: comparison of classifications on 431 unselected patients from a single institution. Blood 98:2935–2941

    Article  PubMed  Google Scholar 

  6. Lee J-H, Lee J-H, Shin J-R, Kim W-K, Chi H-S, Park C-J et al (2003) Application of different prognostic scoring systems and comparison of the FAB and WHO classification in Korean patients with myelodysplastic syndromes. Leukemia 17:305–313

    Article  PubMed  Google Scholar 

  7. Howe B, Porwit-MacDonald A, Wanat R, Tehranchi R, Hellström-Lindberg E (2004) The WHO classification of MDS does make a difference. Blood 103:3265–3270

    Article  CAS  PubMed  Google Scholar 

  8. Malcovati L, Della Porta MG, Pascutto C, Invernizzi R, Boni M, Travaglino E et al (2005) Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol 23:7594–7603

    Article  PubMed  Google Scholar 

  9. Strupp C, Gattermann N, Giagounidis A, Aul C, Hildebrandt B, Haas R, Germing U (2003) Refractory anemia with excess of blasts in transformation: analysis of reclassification according to the WHO proposals. Leuk Res 27:397–404

    Article  PubMed  Google Scholar 

  10. Germing U, Strupp C, Kuendgen A, Aivado M, Giagounidis A, Hildebrandt B et al (2006) Refractory anemia with excess of blasts (RAEB): analysis of reclassification according to the WHO proposals. B J Haematol 132:162–167

    Article  Google Scholar 

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

    PubMed  Google Scholar 

  12. Valent P, Horny HP, Bennet JM, Fonatsch C, Germing U, Greenberg P et al (2007) Definitions and standards in the diagnosis and treatments of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res 31:727–736

    Article  PubMed  Google Scholar 

  13. Mufti GJ, Bennet JM, Goasguen J, Bain BJ, Baumann I, Brunning R et al (2008) Diagnosis and classification of myelodysplastic syndromes: international working group on morphology of myelodysplastic syndrome. Haematologica 93:1712–1717

    Article  PubMed  Google Scholar 

  14. Breccia M, Latagliata R, Cannella L, Carmosino I, De Cuia R, Frustaci A et al (2009) Analysis of prognostic factors in patients with refractory anemia with excess of blasts (RAEB) reclassified according to WHO proposal. Leuk Res 33:391–394

    Article  CAS  PubMed  Google Scholar 

  15. Jädersten M, Hellström-Lindberg E (2008) Myelodysplastic syndromes: biology and treatment. J Int Med 265:307–328

    Article  Google Scholar 

  16. Cazzola M, Malcovati L (2005) Myelodysplastic syndromes – coping with ineffective hematopoiesis. N Engl J Med 352:536–538

    Article  CAS  PubMed  Google Scholar 

  17. Corey SJ, Minden MD, Barber DL, Kantarjian H, Wang JCY, Schimmer AD (2007) Myelodysplastic syndromes: the complexity of stem-cell diseases. Nature Rev Cancer 7:118–129

    Article  CAS  Google Scholar 

  18. Greenberg P, Cox C, Le Beau MM, Fenaux P, Morel P, Sanz G et al (1987) International system for evaluating prognosis in myelodysplastic syndromes. Blood 89:2079–2088

    Google Scholar 

  19. Solè F, Espinet B, Sanz G, Cervera J, Calasanz MJ, Luňo E et al (2000) Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. B J Haematol 108:346–356

    Article  Google Scholar 

  20. Solè F, Luňo E, Sanzo C, Espinet B, Sanz GF, Cervera J et al (2005) Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes. Haematologica 90:1168–1178

    PubMed  Google Scholar 

  21. Bernasconi P, Klersy C, Boni M, Cavigliano PM, Giardini I, Rocca B et al (2005) Incidence and prognostic significance of karyotype abnormalities in de novo primary myelodysplatic syndromes: a study on 331 patients from a single institution. Leukemia 19:1424–1431

    Article  CAS  PubMed  Google Scholar 

  22. Bernasconi P, Klersy C, Boni M, Cavigliano PM, Calatroni S, Giardini I et al (2007) World health organization classification in combination with cytogenetic markers improves the prognostic stratification of patients with de novo primary myelodysplastic syndromes. B J Haematol 137:193–205

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  25. Olney HJ, Le Beau MM (2001) The cytogenetics of myelodysplastic syndromes. Best Pract Res Clin Hematol 14:479–495

    Article  CAS  Google Scholar 

  26. Bernasconi P, Boni M, Cavigliano PM, Calatroni S, Giardini I, Rocca B et al (2006) Clinical relevance of cytogenetics in myelodysplastic syndromes. Ann NY Acad Sci 1089:395–410

    Article  PubMed  Google Scholar 

  27. Tricot G, Boogaerts MA, de Wolf-Peeters C, Van den Berghe H, Verwilghen RL (1985) The myelodysplastic syndromes: different evolution patterns based on sequential morphological and cytogenetic investigations. B J Haematol 59:659–670

    Article  CAS  Google Scholar 

  28. Benitez J, Carbonell F, Sanchez Fayos J, Heimpel H (1985) Karyotypic evolution in patients with myelodysplastic syndromes. Cancer Gen Cytogen 15:157–167

    Article  Google Scholar 

  29. Horiike S, Taniwaki M, Misawa S, Abe T (1988) Chromosome abnormalities and karyotype evolution in 83 patients with myelodysplastic syndrome and predictive value for prognosis. Cancer 62:1129–1138

    Article  CAS  PubMed  Google Scholar 

  30. Suciu S, Kuse R, Weh HJ, Hossfeld DK (1990) Results of chromosome studies and their relation to morphology, course, and prognosis in 120 patients with de novo myelodysplastic syndrome. Cancer Gen Cytogen 44:15–26

    Article  CAS  Google Scholar 

  31. Michalova K, Musilova J, Zemanova Z (1991) Consecutive chromosomal studies in patients with myelodysplastic syndrome (MDS). Czechoslovak MDS Cooperative Group. Ann Genet 34:212–218

    CAS  PubMed  Google Scholar 

  32. White AD, Culligan DJ, Hoy TG, Jacobs A (1992) Extended cytogenetic follow-up of patients with myelodysplastic syndrome (MDS). B J Haematol 81:499–502

    Article  CAS  Google Scholar 

  33. Ghaddar HM, Stass SA, Pierce S, Estey EH (1994) Cytogenetic evolution following the transformation of myelodysplastic syndrome to acute myelogenous leukaemia: implications on the overlap between the two diseases. Leukemia 8:1649–1653

    CAS  PubMed  Google Scholar 

  34. White AD, Hoy TG, Jacobs A (1994) Extended cytogenetic follow-up and clinical progress in patients with myelodysplastic syndromes (MDS). Leuk Lymph 12:401–412

    Article  CAS  Google Scholar 

  35. Tien HF, Wang CH, Chuang SM, Lee FY, Liu MC, Chen YC et al (1995) Acute leukaemic transformation of myelodysplastic syndrome-immunophenotypic, genotypic, and cytogenetic studies. Leuk Res 19:595–603

    Article  CAS  PubMed  Google Scholar 

  36. De Souza FT, Ornellas MH, de Carvalho LO, Tabak D, Abdelhay E (2000) Chromosomal alterations associated with evolution from myelodysplastic syndrome to acute myeloid leukaemia. Leuk Res 24:839–848

    Article  Google Scholar 

  37. Mitelman F. (ed) (1995) ISCN: an international system for human cytogenetic nomenclature. Karger, Basel

  38. Novotna B, Neuwirtova R, Siskova M, Bagryantseva Y (2008) DNA instability in low-risk myelodysplastic syndromes: refractory anemia with or without ring sideroblasts. Hum Mol Genet 17:2144–2149

    Article  CAS  PubMed  Google Scholar 

  39. Bernasconi P (2008) Molecular pathways in myelodysplastic syndromes and acute myeloid leukaemia: relationship and distinctions-a review. Brit J Haematol 142:695–708

    Article  CAS  Google Scholar 

  40. Pomeroy C, Oken MM, Rydell RE, Filice GA (1991) Infection in the myelodysplastic syndromes. Am J Med 90:338–344

    CAS  PubMed  Google Scholar 

  41. Kantarjian H, Giles F, List A, Lyons R, Sekeres MA, Pierce S et al (2007) The incidence and impact of thrombocytopenia in myelodysplastic syndromes. Cancer 109:1705–1714

    Article  CAS  PubMed  Google Scholar 

  42. Germing U, Hildebrandt B, Pfeilstöcker M, Nösslinger T, Valent P, Fonatsch C et al (2005) Refinement of the International Prognostic Scoring System (IPSS) by including LDH as an additional scoring variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS). Leukemia 19:2223–2231

    Article  CAS  PubMed  Google Scholar 

  43. Kao JM, McMillan A, Greenberg P (2008) International MDs risk analysis workshop (IMRAW)/IPSS reanalyzed: impact of cytopenias on clinical outcomes in myelodysplastic syndromes. Am J Hematol 83:765–770

    Article  CAS  PubMed  Google Scholar 

  44. Starczynowski DT, Vercauteren S, Telenius A, Sung S, Tohyama K, Brooks-Wilson A et al (2008) High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival. Blood 112:3412–3424

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Paolo Bernasconi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bernasconi, P., Klersy, C., Boni, M. et al. Does cytogenetic evolution have any prognostic relevance in myelodysplastic syndromes? A study on 153 patients from a single institution. Ann Hematol 89, 545–551 (2010). https://doi.org/10.1007/s00277-010-0927-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-010-0927-z

Keywords

Navigation