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Myelodysplasias (MDS)

Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS)

Leukemia volume 19, pages 2223–2231 (2005)Cite this article

Abstract

The international prognostic scoring system (IPSS) is considered the gold standard for risk assessment in primary myelodysplastic syndromes (MDS). This score includes several prognostic factors except serum lactate dehydrogenase (LDH). We evaluated the prognostic power of LDH as an additional variable in IPSS-based risk assessment. For this purpose, a total of 892 patients with primary MDS registered by the Austrian–German cooperative MDS study group was analyzed retrospectively. Multivariate analysis confirmed the value of established parameters such as medullary blasts, karyotype and peripheral cell counts and showed that elevated LDH was associated with decreased overall survival (P<0.00005) and increased risk of AML development (P<0.00005), independent of the system used to classify MDS (FAB or WHO). Moreover, elevated LDH was found to be a significant predictor of poor survival within each IPSS risk group and within each FAB group except RAEB-T. To exploit these results for refined prognostication, each IPSS risk group was split into two separate categories (A=normal LDH vs B=elevated LDH). Using this LDH-assisted approach, it was possible to identify MDS patients with unfavorable prognosis within the low and intermediate IPSS risk groups. We propose that the IPSS+LDH score should improve clinical decision-making and facilitate proper risk stratification in clinical trials.

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References

  1. Greenberg P, Cox C, Le Beau 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 

  2. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982; 51: 189–199.

    Article  CAS  Google Scholar 

  3. Mufti GJ, Stevens JR, Oscier DG, Hamblin TJ, Machin D . Myelodysplastic syndromes: a scoring system with prognostic significance. Br J Haematol 1985; 59: 425–433.

    Article  CAS  Google Scholar 

  4. Sanz GF, Sanz MA, Vallespi T, Canizo MC, Torrabadella M, Garcia S et al. Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood 1989; 74: 395–408.

    CAS  PubMed  Google Scholar 

  5. Morel P, Hebbar M, Lai JL, Duhamel A, Preudhomme C, Wattel E et al. Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases. Leukemia 1993; 7: 1315–1323.

    CAS  PubMed  Google Scholar 

  6. Aul C, Gattermann N, Heyll A, Germing U, Derigs G, Schneider W . Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. Leukemia 1992; 1: 52–59.

    Google Scholar 

  7. Toyama K, Ohyashiki K, Yoshida Y, Abe T, Asano S, Hirai H et al. Clinical implications of chromosomal abnormalities in 401 patients with myelodysplastic syndromes: a multicentric study in Japan. Leukemia 1993; 7: 499–508.

    CAS  PubMed  Google Scholar 

  8. Parlier V, van Melle G, Beris P, Schmidt PM, Tobler A, Haller E et al. Prediction of 18-month survival in patients with primary myelodysplastic syndrome. A regression model and scoring system based on the combination of chromosome findings and the Bournemouth score. Cancer Genet Cytogenet 1995; 81: 158–165.

    Article  CAS  Google Scholar 

  9. 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  Google Scholar 

  10. Bennett JM . World Health Organization classification of the acute leukemias and myelodysplastic syndrome. Int J Hematol 2000; 72: 131–133.

    CAS  PubMed  Google Scholar 

  11. Germing U, Kuendgen A, Gattermann N . Risk assessment in chronic myelomonocytic leukaemia (CMML). Leuk Lymphoma 2004; 34: 1311–1318.

    Article  Google Scholar 

  12. Pfeilstocker M, Reisner R, Nosslinger T, Gruner H, Nowotny H, Tuchler H et al. Cross-validation of prognostic scores in myelodysplastic syndromes on 386 patients from a single institution confirms importance of cytogenetics. Br J Haematol 1999; 106: 455–463.

    Article  CAS  Google Scholar 

  13. Giagounidis AA, Germing U, Haase S, Hildebrandt B, Schlegelberger B, Schoch C et al. Clinical, morphological, cytogenetic, and prognostic features of patients with myelodysplastic syndromes and del(5q) including band q31. Leukemia 2004; 18: 113–199.

    Article  CAS  Google Scholar 

  14. Aul C, Gattermann N, Germing U, Runde V, Heyll A, Schneider W . Risk assessment in primary myelodysplastic syndromes: validation of the Düsseldorf score. Leukemia 1994; 8: 1906–1913.

    CAS  PubMed  Google Scholar 

  15. Wimazal F, Sperr WR, Kundi M, Meidlinger P, Fonatsch C, Jordan JH et al. Prognostic value of lactate dehydrogenase activity in myelodysplastic syndromes. Leuk Res 2001; 25: 287–294.

    Article  CAS  Google Scholar 

  16. Sperr WR, Wimazal F, Kundi M, Fonatsch C, Thalhammer-Scherrer R, Schernthaler GH et al. Survival analysis and AML development in patients with de novo myelodysplastic syndromes: comparison of six different prognostic scoring systems. Ann Hematol 2001; 80: 272–275.

    Article  CAS  Google Scholar 

  17. Gonzalez-Medina I, Bueno J, Torrequebrada A, Lopez A, Vallespi T, Massague I . Two groups of chronic myelomonocytic leukaemia: myelodysplastic and myeloproliferative. Prognostic implications in a series of a single center. Leuk Res 2002; 26: 821–824.

    Article  CAS  Google Scholar 

  18. Onida F, Kantarjian HM, Smith TL, Ball G, Keating MJ, Estey EH et al. Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients. Blood 2002; 99: 840–849.

    Article  CAS  Google Scholar 

  19. Sole F, Espinet B, Sanz GF, Cervera J, Calasanz MJ, Luno E et al. Incidence, characterization and prognostic significance of chromosomal abnormalities in 640 patients with primary myelodysplastic syndromes. Grupo Cooperativo Espanol de Citogenetica Hematologica. Br J Haematol 2000; 108: 346–356.

    Article  CAS  Google Scholar 

  20. Haase D, Fonatsch C, Freund M, Wormann B, Bodenstein H, Bartels H et al. Cytogenetic findings in 179 patients with myelodysplastic syndromes. Ann Hematol 1995; 70: 171–187.

    Article  CAS  Google Scholar 

  21. Oguma S, Yoshida Y, Uchino H, Maekawa T, Nomura T, Mizogushi H . Clinical characteristics of Japanese patients with primary myelodysplastic syndromes: a co-operative study based on 838 cases. Leuk Res 1995; 19: 219–225.

    Article  CAS  Google Scholar 

  22. Lee JH, Lee JH, Shin YR, Lee JS, Kim WK, Chi HS et al. Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome. Leukemia 2003; 17: 305–313.

    Article  Google Scholar 

  23. 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  Google Scholar 

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Acknowledgements

The authors thank Gisele Rocco, Manuel Aivado, Julie Schanz, Jurij Pitako, Wolfgang R. Sperr, Friedrich Wimazal, and Helga Grüner for their assistance in data collection and karyotyping. This work was supported by Kompetenznetz ‘Akute und chronische Leukämien’, Bundesforschungsministerium (German Research Ministry). R.S. was supported by ‘Tiroler Verein zur Förderung der Krebsforschung an der Universitätsklinik Innsbruck’ und ‘Johannes und Hertha Tuba-Stiftung’, Innsbruck, Austria.

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Authors and Affiliations

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

    U Germing, C Strupp, A Kündgen, R Haas & N Gattermann

  2. Department of Human Genetics, Heinrich-Heine-University, Germany

    B Hildebrandt

  3. L. Boltzmann Institute für Leukämieforschung und Hämatologie, Hanusch-Spital Vienna, Austria

    M Pfeilstöcker & T Nösslinger

  4. Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Austria

    P Valent

  5. Department of Human Genetics, Medical University of Vienna, Austria

    C Fonatsch

  6. Department of Hematology, University of Freiburg, Germany

    M Lübbert

  7. Department of Human Genetics, University of Freiburg, Germany

    M Lübbert

  8. Department of Hematology, Georg-August University of Göttingen, Germany

    D Haase & C Steidl

  9. Department of Hematology, Elisabethinen Hospital Linz, Austria

    O Krieger

  10. Department of Hematology, University of Innsbruck, Austria

    R Stauder

  11. Department of Hematology, Oncology and Clinical Immunology, St Johannes-Hospital Duisburg, Germany

    A A N Giagounidis & C Aul

  12. Department of Biostatistics, University of München, Germany

    T Mueller

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  1. U Germing
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  14. A Kündgen
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  15. T Mueller
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  16. R Haas
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  17. N Gattermann
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Correspondence to U Germing.

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Germing, U., Hildebrandt, B., Pfeilstöcker, M. et al. Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS). Leukemia 19, 2223–2231 (2005). https://doi.org/10.1038/sj.leu.2403963

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