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Myelodysplasia

Multicenter validation study of a transplantation-specific cytogenetics grouping scheme for patients with myelodysplastic syndromes

Bone Marrow Transplantation volume 45, pages 877–885 (2010)Cite this article

Abstract

Cytogenetics is an important prognostic factor for patients with myelodysplastic syndromes (MDS). However, existing cytogenetics grouping schemes are based on patients treated with supportive care, and may not be optimal for patients undergoing allo-SCT. We proposed earlier an SCT-specific cytogenetics grouping scheme for patients with MDS and AML arising from MDS, based on an analysis of patients transplanted at the Dana-Farber Cancer Institute/Brigham and Women's Hospital. Under this scheme, abnormalities of chromosome 7 and complex karyotype are considered adverse risk, whereas all others are considered standard risk. In this retrospective study, we validated this scheme on an independent multicenter cohort of 546 patients. Adverse cytogenetics was the strongest prognostic factor for outcome in this cohort. The 4-year relapse-free survival and OS were 42 and 46%, respectively, in the standard-risk group, vs 21 and 23% in the adverse group (P<0.0001 for both comparisons). This grouping scheme retained its prognostic significance irrespective of patient age, disease type, earlier leukemogenic therapy and conditioning intensity. Therapy-related disease was not associated with increased mortality in this cohort, after taking cytogenetics into account. We propose that this SCT-specific cytogenetics grouping scheme be used for patients with MDS or AML arising from MDS who are considering or undergoing SCT.

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References

  1. Nowell PC, Besa EC, Stelmach T, Finan JB . Chromosome studies in preleukemic states. V. Prognostic significance of single versus multiple abnormalities. Cancer 1986; 58: 2571–2575.

    Article  CAS  PubMed  Google Scholar 

  2. 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 

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

    CAS  PubMed  Google Scholar 

  4. Haase D, Germing U, Schanz J, Pfeilstocker M, Nosslinger 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 

  5. Nevill TJ, Fung HC, Shepherd JD, Horsman DE, Nantel SH, Klingemann HG et al. Cytogenetic abnormalities in primary myelodysplastic syndrome are highly predictive of outcome after allogeneic bone marrow transplantation. Blood 1998; 92: 1910–1917.

    CAS  PubMed  Google Scholar 

  6. Alessandrino EP, Della Porta MG, Bacigalupo A, Van Lint MT, Falda M, Onida F et al. WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Blood 2008; 112: 895–902.

    Article  CAS  PubMed  Google Scholar 

  7. Chang C, Storer BE, Scott BL, Bryant EM, Shulman HM, Flowers ME et al. Hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute myeloid leukemia arising from myelodysplastic syndrome: similar outcomes in patients with de novo disease and disease following prior therapy or antecedent hematologic disorders. Blood 2007; 110: 1379–1387.

    Article  CAS  PubMed  PubMed Central  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. Bernasconi P, Klersy C, Boni M, Cavigliano PM, Calatroni S, Giardini I et al. World Health Organization classification in combination with cytogenetic markers improves the prognostic stratification of patients with de novo primary myelodysplastic syndromes. Br J Haematol 2007; 137: 193–205.

    Article  CAS  PubMed  Google Scholar 

  10. Armand P, Kim HT, DeAngelo DJ, Ho VT, Cutler CS, Stone RM et al. Impact of cytogenetics on outcome of de novo and therapy-related AML and MDS after allogeneic transplantation. Biol Blood Marrow Transplant 2007; 13: 655–664.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al. WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues. In: Bosman FT, Jaffe ES, Lakhani SR, Ohgaki H (eds). 4th edn. International Agency for Research on Cancer: Lyon, 2008.

  12. Gray R . A class of K-sample tests for comparing the cumulative incidence of a competing risk. Ann Stat 1988; 16: 1140–1154.

    Article  Google Scholar 

  13. Fine J, Gray R . A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999; 94: 496–509.

    Article  Google Scholar 

  14. Vardiman JW, Harris NL, Brunning RD . The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002; 100: 2292–2302.

    Article  CAS  PubMed  Google Scholar 

  15. Breems DA, Van Putten WL, De Greef GE, Van Zelderen-Bhola SL, Gerssen-Schoorl KB, Mellink CH et al. Monosomal karyotype in acute myeloid leukemia: a better indicator of poor prognosis than a complex karyotype. J Clin Oncol 2008; 26: 4791–4797.

    Article  PubMed  Google Scholar 

  16. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children′s Leukaemia Working Parties. Blood 1998; 92: 2322–2333.

    CAS  PubMed  Google Scholar 

  17. Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002; 100: 4325–4336.

    Article  CAS  PubMed  Google Scholar 

  18. Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 2000; 96: 4075–4083.

    CAS  PubMed  Google Scholar 

  19. Yilmaz Z, Sahin FI, Kizilkilic E, Karakus S, Boga C, Ozdogu H . Conventional and molecular cytogenetic findings of myelodysplastic syndrome patients. Clin Exp Med 2005; 5: 55–59.

    Article  CAS  PubMed  Google Scholar 

  20. Vance GH, Kim H, Hicks GA, Cherry AM, Higgins R, Hulshizer RL et al. Utility of interphase FISH to stratify patients into cytogenetic risk categories at diagnosis of AML in an Eastern Cooperative Oncology Group (ECOG) clinical trial (E1900). Leuk Res 2007; 31: 605–609.

    Article  CAS  PubMed  Google Scholar 

  21. Kracmarova A, Cermak J, Brdicka R, Bruchova H . High expression of ERCC1, FLT1, NME4 and PCNA associated with poor prognosis and advanced stages in myelodysplastic syndrome. Leuk Lymphoma 2008; 49: 1297–1305.

    Article  CAS  PubMed  Google Scholar 

  22. Hu Q, Dey AL, Yang Y, Shen Y, Jilani IB, Estey EH et al. Soluble vascular endothelial growth factor receptor 1, and not receptor 2, is an independent prognostic factor in acute myeloid leukemia and myelodysplastic syndromes. Cancer 2004; 100: 1884–1891.

    Article  CAS  PubMed  Google Scholar 

  23. Scott BL, Wells DA, Loken MR, Myerson D, Leisenring WM, Deeg HJ . Validation of a flow cytometric scoring system as a prognostic indicator for posttransplantation outcome in patients with myelodysplastic syndrome. Blood 2008; 112: 2681–2686.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. van de Loosdrecht AA, Westers TM, Westra AH, Drager AM, van der Velden VH, Ossenkoppele GJ . Identification of distinct prognostic subgroups in low- and intermediate-1-risk myelodysplastic syndromes by flow cytometry. Blood 2008; 111: 1067–1077.

    Article  CAS  PubMed  Google Scholar 

  25. Rowley JD, Golomb HM, Vardiman JW . Nonrandom chromosome abnormalities in acute leukemia and dysmyelopoietic syndromes in patients with previously treated malignant disease. Blood 1981; 58: 759–767.

    CAS  PubMed  Google Scholar 

  26. Mauritzson N, Albin M, Rylander L, Billstrom R, Ahlgren T, Mikoczy Z et al. Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976-1993 and on 5098 unselected cases reported in the literature 1974-2001. Leukemia 2002; 16: 2366–2378.

    Article  CAS  PubMed  Google Scholar 

  27. Smith SM, Le Beau MM, Huo D, Karrison T, Sobecks RM, Anastasi J et al. Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood 2003; 102: 43–52.

    Article  CAS  PubMed  Google Scholar 

  28. Kantarjian HM, Keating MJ, Walters RS, Smith TL, Cork A, McCredie KB et al. Therapy-related leukemia and myelodysplastic syndrome: clinical, cytogenetic, and prognostic features. J Clin Oncol 1986; 4: 1748–1757.

    Article  CAS  PubMed  Google Scholar 

  29. Michels SD, McKenna RW, Arthur DC, Brunning RD . Therapy-related acute myeloid leukemia and myelodysplastic syndrome: a clinical and morphologic study of 65 cases. Blood 1985; 65: 1364–1372.

    CAS  PubMed  Google Scholar 

  30. Josting A, Wiedenmann S, Franklin J, May M, Sieber M, Wolf J et al. Secondary myeloid leukemia and myelodysplastic syndromes in patients treated for Hodgkin's disease: a report from the German Hodgkin's Lymphoma Study Group. J Clin Oncol 2003; 21: 3440–3446.

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was funded in part by NIAID U19 AI 29530, PO1 HL070149 from the National Heart, Lung and Blood Institute, and the Ted and Eileen Pasquarello Research Fund. PA is also supported by a fellowship from the Leukemia and Lymphoma Society. HJD is supported by NIH grants HL036444, HL082941 and CA018029.

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Authors and Affiliations

  1. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    P Armand & R J Soiffer

  2. Clinical Research Division, Transplantation Biology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    H J Deeg

  3. Department of Biostatistics, Dana-Farber Cancer Institute, Boston, MA, USA

    H T Kim

  4. Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, NY, USA

    H Lee

  5. Department of Stem Cell Transplantation and Cell Therapy, MD Anderson Cancer Center, Houston, TX, USA

    P Armistead & M de Lima

  6. Department of Medicine, Princess Margaret Hospital, Toronto, Ontario, Canada

    V Gupta

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  1. P Armand
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Correspondence to P Armand.

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Armand, P., Deeg, H., Kim, H. et al. Multicenter validation study of a transplantation-specific cytogenetics grouping scheme for patients with myelodysplastic syndromes. Bone Marrow Transplant 45, 877–885 (2010). https://doi.org/10.1038/bmt.2009.253

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