Leukemia Research
Volume 36, Issue 3 , Pages 264-270 , March 2012

Update on developments in the diagnosis and prognostic evaluation of patients with myelodysplastic syndromes (MDS): Consensus statements and report from an expert workshop

  • Uwe Platzbecker

      Affiliations

    • Universitätsklinikum Carl-Gustav-Carus, Medizinische Klinik I, Dresden 01307, Germany
    • Corresponding Author InformationCorresponding author. Tel.: +49 351 458 4190; fax: +49 351 458 5362.
  • ,
  • Valeria Santini

      Affiliations

    • AOU Careggi, University of Florence, Italy
  • ,
  • Ghulam J. Mufti

      Affiliations

    • Kings College London and Kings College Hospital, Department of Haematological Medicine, London, UK
  • ,
  • Claudia Haferlach

      Affiliations

    • MLL Munich Leukemia Laboratory, Munich, Germany
  • ,
  • Jaroslaw P. Maciejewski

      Affiliations

    • Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
  • ,
  • Sophie Park

      Affiliations

    • Hôpital Cochin, Université, Paris V, Assistance Publique des Hopitaux de Paris, Paris, France
  • ,
  • Francesc Solé

      Affiliations

    • Hospital del Mar-Parc de Salut Mar, Barcelona, Spain
  • ,
  • Arjan A. van de Loosdrecht

      Affiliations

    • Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands
  • ,
  • Detlef Haase

      Affiliations

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

Received 15 September 2011 ,Revised 7 November 2011 ,Accepted 8 November 2011.

References 

  1. Malcovati L, Nimer SD. Myelodysplastic syndromes: diagnosis and staging. Cancer Control. 2008;15(Suppl.):4–13
  2. Bacher U, Haferlach T, Kern W, Weiss T, Schnittger S, Haferlach C. The impact of cytomorphology, cytogenetics, molecular genetics, and immunophenotyping in a comprehensive diagnostic workup of myelodysplastic syndromes. Cancer. 2009;115:4524–4532
  3. Catenacci DV, Schiller GJ. Myelodysplasic syndromes: a comprehensive review. Blood Rev. 2005;19:301–319
  4. Komrokji RS, Bennett JM. Evolving classifications of the myelodysplastic syndromes. Curr Opin Hematol. 2007;14:98–105
  5. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10:223–232
  6. Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006;106:1794–1803
  7. List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006;355:1456–1465
  8. Sloand EM, Wu CO, Greenberg P, Young N, Barrett J. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol. 2008;26:2505–2511
  9. 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
  10. Schanz J, Tüchler F, Sole F, Mallo M, Hildebrandt B, Slovak M, et al. Proposal of a new, comprehensive cytogenetic scoring system for primary MDS. Haematologica. 2010;95(Suppl. 2):219;[Abstract 0535]
  11. Tricot G, Boogaerts MA, De Wolf-Peeters C, Van den Berghe H, Verwilghen RL. The myelodysplastic syndromes: different evolution patterns based on sequential morphological and cytogenetic investigations. Br J Haematol. 1985;59:659–670
  12. Valent P, Horny HP, Bennett JM, Fonatsch C, Germing U, Greenberg P, et al. Definitions and standards in the diagnosis and treatment of the myelodysplastic syndromes: consensus statements and report from a working conference. Leuk Res. 2007;31:727–736
  13. 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
  14. Santini V, Alessandrino PE, Angelucci E, Barosi G, Billio A, Di MM, et al. Clinical management of myelodysplastic syndromes: update of SIE, SIES, GITMO practice guidelines. Leuk Res. 2010;34:1576–1588
  15. Valent P, Orazi A, Busche G, Schmitt-Graff A, George TI, Sotlar K, et al. Standards and impact of hematopathology in myelodysplastic syndromes (MDS). Oncotarget. 2010;1:483–496
  16. Steidl C, Steffens R, Gassmann W, Hildebrandt B, Hilgers R, Germing U, et al. Adequate cytogenetic examination in myelodysplastic syndromes: analysis of 529 patients. Leuk Res. 2005;29:987–993
  17. Braulke F, Schanz J, Jung K, Shirneshan K, Schulte K, Schuetze C, et al. FISH analysis of circulating CD34+ cells as a new tool for genetic monitoring in MDS: verification of the method and application to 27 MDS patients. Leuk Res. 2010;34:1296–1301
  18. Galvan AB, Mallo M, Arenillas L, Salido M, Espinet B, Pedro C, et al. Does monosomy 5 really exist in myelodysplastic syndromes and acute myeloid leukemia?. Leuk Res. 2010;34:1242–1245
  19. Mallo M, Arenillas L, Espinet B, Salido M, Hernandez JM, Lumbreras E, et al. Fluorescence in situ hybridization improves the detection of 5q31 deletion in myelodysplastic syndromes without cytogenetic evidence of 5q-. Haematologica. 2008;93:1001–1008
  20. Cherry AM, Slovak ML, Campbell LJ, Chun K, Eclache V, Haase D, et al. Will a peripheral blood (PB) sample yield the same diagnostic and prognostic cytogenetic data as the concomitant bone marrow (BM) on myelodysplasia? An international study comparing cytogenetics and interphase FISH using parallel PB and BM samples. Blood. 2010;116:[Abstract 2922]
  21. Gohring G, Giagounidis A, Busche G, Hofmann W, Kreipe HH, Fenaux P, et al. Cytogenetic follow-up by karyotyping and fluorescence in situ hybridization: implications for monitoring patients with myelodysplastic syndrome and deletion 5q treated with lenalidomide. Haematologica. 2011;96:319–322
  22. Braulke F, Schanz J, Detken S, Seraphin J, Metz M, Brümmerdörf T, et al. Detection of rare abnormalities and karyotype evolution in MDS patients from peripheral blood: first results from The Mulitcenter German Prospective Diagnostic CD34+FISH-Study. Haematologica. 2010;95:219;[Abstract 0536]
  23. 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
  24. van de Loosdrecht AA, Alhan C, Bene MC, la Porta MG, Drager AM, Feuillard J, et al. Standardization of flow cytometry in myelodysplastic syndromes: report from the first European LeukemiaNet working conference on flow cytometry in myelodysplastic syndromes. Haematologica. 2009;94:1124–1134
  25. Wells DA, Benesch M, Loken MR, Vallejo C, Myerson D, Leisenring WM, et al. Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation. Blood. 2003;102:394–403
  26. 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
  27. Westers TM, Alhan C, Chamuleau ME, van der Vorst MJ, Eeltink C, Ossenkoppele GJ, et al. Aberrant immunophenotype of blasts in myelodysplastic syndromes is a clinically relevant biomarker in predicting response to growth factor treatment. Blood. 2010;115:1779–1784
  28. Alhan C, Westers TM, Eeltink C, Cali C, Ossenkoppele GJ, Van de Loosdrecht AA. Flow cytometric score correlates with clinical response to azacitidine in intermediate-2 and high risk myelodysplastic syndrome patients. Blood. 2010;116:[Abstract 441]
  29. Maciejewski JP, Mufti GJ. Whole genome scanning as a cytogenetic tool in hematologic malignancies. Blood. 2008;112:965–974
  30. Mohamedali A, Gaken J, Twine NA, Ingram W, Westwood N, Lea NC, et al. Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes. Blood. 2007;110:3365–3373
  31. Gondek LP, Tiu R, O’Keefe CL, Sekeres MA, Theil KS, Maciejewski JP. Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML. Blood. 2008;111:1534–1542
  32. Mohamedali AM, Smith AE, Gaken J, Lea NC, Mian SA, Westwood NB, et al. Novel TET2 mutations associated with UPD4q24 in myelodysplastic syndrome. J Clin Oncol. 2009;27:4002–4006
  33. Delhommeau F, Dupont S, Della VV, James C, Trannoy S, Masse A, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360:2289–2301
  34. Langemeijer SM, Kuiper RP, Berends M, Knops R, Aslanyan MG, Massop M, et al. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet. 2009;41:838–842
  35. Gelsi-Boyer V, Trouplin V, Adelaide J, Bonansea J, Cervera N, Carbuccia N, et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol. 2009;145:788–800
  36. Nikoloski G, Langemeijer SM, Kuiper RP, Knops R, Massop M, Tonnissen ER, et al. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat Genet. 2010;42:665–667
  37. Garcia-Manero G. Prognosis of myelodysplastic syndromes. Hematology Am Soc Hematol Educ Program 2010. 2010;330–337
  38. Kulasekararaj AG, Mohamedali AM, Smith AE, Lea NC, Kizilors A, Abdallah A, et al. Polycomb complex group gene mutations and their prognostic relevance in 5-azacitidine treated myelodysplastic syndrome patients. Blood. 2010;116:[Abstract 125]
  39. Jadersten M, Saft L, Pellagatti A, Gohring 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
  40. Itzykson R, Kosmider O, Cluzeau T, Mansat-De MV, Dreyfus F, Beyne-Rauzy O, et al. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia. 2011;April 15 [Epub ahead of print]
  41. Smith AE, Mohamedali AM, Kulasekararaj A, Lim Z, Gaken J, Lea NC, et al. Next-generation sequencing of the TET2 gene in 355 MDS and CMML patients reveals low-abundance mutant clones with early origins, but indicates no definite prognostic value. Blood. 2010;116:3923–3932
  42. Mills KI, Kohlmann A, Williams PM, Wieczorek L, Liu WM, Li R, et al. Microarray-based classifiers and prognosis models identify subgroups with distinct clinical outcomes and high risk of AML transformation of myelodysplastic syndrome. Blood. 2009;114:1063–1072
  43. Malcovati L, Germing U, Kuendgen A, la 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
  44. Gale RP, Barosi G, Barbui T, Cervantes F, Dohner K, Dupriez B, et al. What are RBC-transfusion-dependence and -independence?. Leuk Res. 2011;35:8–11
  45. Malcovati L, la Porta MG, Strupp C, Ambaglio I, Kuendgen A, Nachtkamp K, et al. Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based Prognostic Scoring System (WPSS). Haematologica. 2011;June 9 [Epub ahead of print]
  46. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937–951
  47. Greenberg P, Tuechler H, Schanz J, et al. Revised International Prognostic Scoring System (IPSS-R), developed by the International Prognostic Working Group for Prognosis in MDS (lWG-PM). Leuk Res. 2011;35:S6
  48. Bernasconi P, Klersy C, Boni M, Dambruoso I, Zappatore R, Cavigliano P, et al. The International Multicentric Cooperation cytogenetic scoring system effectively predicts disease outcome in de novo MDS. Haematologica. 2011;96(S2):99
  49. Makishima H, Rataul M, Gondek LP, Huh J, Cook JR, Theil KS, et al. FISH and SNP-A karyotyping in myelodysplastic syndromes: improving cytogenetic detection of del(5q), monosomy 7, del(7q), trisomy 8 and del(20q). Leuk Res. 2010;34:447–453

PII: S0145-2126(11)00537-6

doi: 10.1016/j.leukres.2011.11.005

Leukemia Research
Volume 36, Issue 3 , Pages 264-270 , March 2012