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Prognosis of the myelodysplastic syndromes in adults

Authors
Elihu H Estey, MD
Stanley L Schrier, MD
Section Editor
Richard A Larson, MD
Deputy Editor
Alan G Rosmarin, MD

INTRODUCTION

The myelodysplastic syndromes (MDS) encompass a series of hematologic conditions characterized by chronic cytopenias (anemia, neutropenia, thrombocytopenia) accompanied by abnormal cellular maturation. As a result, patients with MDS are at risk for symptomatic anemia, infection, and bleeding, as well as progression to acute myeloid leukemia (AML), which is often refractory to standard treatment.

Most patients with MDS die because of the consequences of bone marrow failure, rather than transformation to AML. Thus, use of such terms as "pre-leukemia" or "smoldering leukemia" can be misleading, if taken to imply that death or morbidity from MDS results only when AML develops. Indeed, the distinction between MDS and AML is itself arbitrary, as patients with 20 to 30 percent blasts in the marrow were considered to have MDS by French-American-British (FAB) criteria, but AML by the World Health Organization (WHO). (See "Clinical manifestations and diagnosis of the myelodysplastic syndromes", section on 'Acute myeloid leukemia'.)

The natural history of patients with MDS is varied. This heterogeneity reflects both known and unknown differences in the pathobiology of specific subtypes within MDS and patient related characteristics, such as age and prior exposure to chemotherapy. While the pathologic classification systems (eg, French American British classification system and WHO classification system) have been valuable as benchmarks for diagnosis, they have been less useful for the determination of prognosis. As a result, further dissection of these classification schemes has been performed, taking into account variables such as age and sex, morphologic features, blast percentage, clinical characteristics, the presence of cytopenias, transfusion requirements, and cytogenetic abnormalities.

There are three main prognostic systems that have been developed and validated in patients with MDS:

International prognostic scoring system (IPSS) and a revised IPSS (IPSS-R)

              

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Literature review current through: Nov 2016. | This topic last updated: Fri Sep 16 00:00:00 GMT+00:00 2016.
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References
Top
  1. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis 2011; 52:e56.
  2. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89:2079.
  3. Onida F, Kantarjian HM, Smith TL, et al. Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients. Blood 2002; 99:840.
  4. Beran M, Wen S, Shen Y, et al. Prognostic factors and risk assessment in chronic myelomonocytic leukemia: validation study of the M.D. Anderson Prognostic Scoring System. Leuk Lymphoma 2007; 48:1150.
  5. Such E, Germing U, Malcovati L, et al. Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia. Blood 2013; 121:3005.
  6. Germing U, Strupp C, Aivado M, Gattermann N. New prognostic parameters for chronic myelomonocytic leukemia. Blood 2002; 100:731.
  7. Swerdlow SH, Campo E, Harris NL, et al. World Health Organization classification of tumours of haematopoietic and lymphoid tissues, IARC Press, Lyon 2008.
  8. Greenberg, PL. Myelodysplastic Syndrome. In: Hematology: Basic Principles and Practice, 3rd, Hoffman, R, Benz, EJ, Shattil, SJ (Eds), Churchill Livingstone, New York 2000. p.1106.
  9. Sanz GF, Sanz MA, Vallespí T, 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.
  10. Schanz J, Tüchler H, Solé F, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol 2012; 30:820.
  11. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012; 120:2454.
  12. Kuendgen A, Strupp C, Aivado M, et al. Myelodysplastic syndromes in patients younger than age 50. J Clin Oncol 2006; 24:5358.
  13. Voso MT, Fenu S, Latagliata R, et al. Revised International Prognostic Scoring System (IPSS) predicts survival and leukemic evolution of myelodysplastic syndromes significantly better than IPSS and WHO Prognostic Scoring System: validation by the Gruppo Romano Mielodisplasie Italian Regional Database. J Clin Oncol 2013; 31:2671.
  14. Della Porta MG, Alessandrino EP, Bacigalupo A, et al. Predictive factors for the outcome of allogeneic transplantation in patients with MDS stratified according to the revised IPSS-R. Blood 2014; 123:2333.
  15. Gangat N, Patnaik MM, Begna K, et al. Primary Myelodysplastic Syndromes: The Mayo Clinic Experience With 1000 Patients. Mayo Clin Proc 2015; 90:1623.
  16. Koenecke C, Göhring G, de Wreede LC, et al. Impact of the revised International Prognostic Scoring System, cytogenetics and monosomal karyotype on outcome after allogeneic stem cell transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia evolving from myelodysplastic syndromes: a retrospective multicenter study of the European Society of Blood and Marrow Transplantation. Haematologica 2015; 100:400.
  17. Komrokji, RS, Bennett, JM. What is "WHO"? Myelodysplastic syndromes classification. Clinical Leukemia 2008; 2:20.
  18. Garcia-Manero G. Prognosis of myelodysplastic syndromes. Hematology Am Soc Hematol Educ Program 2010; 2010:330.
  19. Yoshimi A, Abdel-Wahab O. Defining risk in MDS over time. Blood 2016; 128:885.
  20. Pfeilstöcker M, Tuechler H, Sanz G, et al. Time-dependent changes in mortality and transformation risk in MDS. Blood 2016; 128:902.
  21. Schanz J, Steidl C, Fonatsch C, et al. Coalesced multicentric analysis of 2,351 patients with myelodysplastic syndromes indicates an underestimation of poor-risk cytogenetics of myelodysplastic syndromes in the international prognostic scoring system. J Clin Oncol 2011; 29:1963.
  22. Solé F, Luño E, Sanzo C, et al. Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes. Haematologica 2005; 90:1168.
  23. Steidl, C, Schanz, J, Pfeilstocker, M, et al. Growing evidence for an underestimation of poor-risk cytogenetics in the International Prognostic Scoring System in myelodysplastic syndromes. Clin Leukemia 2007; 1:353.
  24. Garcia-Manero G, Shan J, Faderl S, et al. A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia 2008; 22:538.
  25. Itzykson R, Thépot S, Quesnel B, et al. Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood 2011; 117:403.
  26. Sekeres MA. Bone marrow transplantation (BMT) in myelodysplastic syndromes: to BMT or not to BMT--that is the question. J Clin Oncol 2013; 31:2643.
  27. Malcovati L, Porta MG, Pascutto C, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol 2005; 23:7594.
  28. Remacha AF, Arrizabalaga B, Del Cañizo C, et al. Iron overload and chelation therapy in patients with low-risk myelodysplastic syndromes with transfusion requirements. Ann Hematol 2010; 89:147.
  29. Malcovati L, Germing U, Kuendgen A, et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol 2007; 25:3503.
  30. Alessandrino EP, Della Porta MG, Bacigalupo A, 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.
  31. Vardiman JW, Thiele J, Arber DA, 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.
  32. Kantarjian H, O'Brien S, Ravandi F, et al. Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System. Cancer 2008; 113:1351.
  33. Komrokji RS, Corrales-Yepez M, Al Ali N, et al. Validation of the MD Anderson Prognostic Risk Model for patients with myelodysplastic syndrome. Cancer 2012; 118:2659.
  34. Walter RB, Othus M, Paietta EM, et al. Effect of genetic profiling on prediction of therapeutic resistance and survival in adult acute myeloid leukemia. Leukemia 2015; 29:2104.
  35. Christiansen DH, Andersen MK, Pedersen-Bjergaard J. Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis. J Clin Oncol 2001; 19:1405.
  36. Kita-Sasai Y, Horiike S, Misawa S, et al. International prognostic scoring system and TP53 mutations are independent prognostic indicators for patients with myelodysplastic syndrome. Br J Haematol 2001; 115:309.
  37. Padua RA, Guinn BA, Al-Sabah AI, et al. RAS, FMS and p53 mutations and poor clinical outcome in myelodysplasias: a 10-year follow-up. Leukemia 1998; 12:887.
  38. Wattel E, Preudhomme C, Hecquet B, et al. p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. Blood 1994; 84:3148.
  39. Jädersten M, Saft L, Smith A, et al. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol 2011; 29:1971.
  40. Bejar R, Stevenson K, Abdel-Wahab O, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 2011; 364:2496.
  41. Koh Y, Lee HR, Song EY, et al. Hypoplastic myelodysplastic syndrome (h-MDS) is a distinctive clinical entity with poorer prognosis and frequent karyotypic and FISH abnormalities compared to aplastic anemia (AA). Leuk Res 2010; 34:1344.
  42. Tong WG, Quintás-Cardama A, Kadia T, et al. Predicting survival of patients with hypocellular myelodysplastic syndrome: development of a disease-specific prognostic score system. Cancer 2012; 118:4462.
  43. Tiu RV, Gondek LP, O'Keefe CL, et al. Prognostic impact of SNP array karyotyping in myelodysplastic syndromes and related myeloid malignancies. Blood 2011; 117:4552.
  44. Itzykson R, Thépot S, Quesnel B, et al. Long-term outcome of higher-risk MDS patients treated with azacitidine: an update of the GFM compassionate program cohort. Blood 2012; 119:6172.
  45. Sperr WR, Wimazal F, Kundi M, et al. Comorbidity as prognostic variable in MDS: comparative evaluation of the HCT-CI and CCI in a core dataset of 419 patients of the Austrian MDS Study Group. Ann Oncol 2010; 21:114.
  46. Breccia M, Federico V, Latagliata R, et al. Evaluation of comorbidities at diagnosis predicts outcome in myelodysplastic syndrome patients. Leuk Res 2011; 35:159.
  47. Della Porta MG, Malcovati L, Strupp C, et al. Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome. Haematologica 2011; 96:441.
  48. Naqvi K, Garcia-Manero G, Sardesai S, et al. Association of comorbidities with overall survival in myelodysplastic syndrome: development of a prognostic model. J Clin Oncol 2011; 29:2240.
  49. Wimazal F, Germing U, Kundi M, et al. Evaluation of the prognostic significance of eosinophilia and basophilia in a larger cohort of patients with myelodysplastic syndromes. Cancer 2010; 116:2372.
  50. Jacobs NL, Holtan SG, Porrata LF, et al. Host immunity affects survival in myelodysplastic syndromes: Independent prognostic value of the absolute lymphocyte count. Am J Hematol 2010; 85:160.
  51. Kao JM, McMillan A, Greenberg PL. International MDS risk analysis workshop (IMRAW)/IPSS reanalyzed: impact of cytopenias on clinical outcomes in myelodysplastic syndromes. Am J Hematol 2008; 83:765.
  52. Breccia M, Latagliata R, Cannella L, et al. Refractory cytopenia with unilineage dysplasia: analysis of prognostic factors and survival in 126 patients. Leuk Lymphoma 2010; 51:783.
  53. Gonzalez-Porras JR, Cordoba I, Such E, et al. Prognostic impact of severe thrombocytopenia in low-risk myelodysplastic syndrome. Cancer 2011; 117:5529.
  54. Cazzola M, Malcovati L. Myelodysplastic syndromes--coping with ineffective hematopoiesis. N Engl J Med 2005; 352:536.
  55. Balducci L. Transfusion independence in patients with myelodysplastic syndromes: impact on outcomes and quality of life. Cancer 2006; 106:2087.
  56. Starczynowski DT, Vercauteren S, Telenius A, et al. 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 2008; 112:3412.
  57. Della Porta MG, Malcovati L, Boveri E, et al. Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes. J Clin Oncol 2009; 27:754.
  58. Mills KI, Kohlmann A, Williams PM, 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.
  59. Pellagatti A, Benner A, Mills KI, et al. Identification of gene expression-based prognostic markers in the hematopoietic stem cells of patients with myelodysplastic syndromes. J Clin Oncol 2013; 31:3557.
  60. Shen L, Kantarjian H, Guo Y, et al. DNA methylation predicts survival and response to therapy in patients with myelodysplastic syndromes. J Clin Oncol 2010; 28:605.
  61. Jabbour E, Garcia-Manero G, Batty N, et al. Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy. Cancer 2010; 116:3830.
  62. Tennant GB, Al-Sabah AI, Burnett AK. Prognosis of myelodysplasic patients: non-parametric multiple regression analysis of populations stratified by mean corpuscular volume and marrow myeloblast number. Br J Haematol 2002; 119:87.
  63. Wang H, Wang X, Xu X, Lin G. Mean corpuscular volume predicts prognosis in MDS patients with abnormal karyotypes. Ann Hematol 2010; 89:671.
  64. Cilloni D, Gottardi E, Messa F, et al. Significant correlation between the degree of WT1 expression and the International Prognostic Scoring System Score in patients with myelodysplastic syndromes. J Clin Oncol 2003; 21:1988.
  65. Galimberti S, Ghio F, Guerrini F, et al. WT1 expression levels at diagnosis could predict long-term time-to-progression in adult patients affected by acute myeloid leukaemia and myelodysplastic syndromes. Br J Haematol 2010; 149:451.
  66. Pellagatti A, Marafioti T, Paterson JC, et al. Marked downregulation of the granulopoiesis regulator LEF1 is associated with disease progression in the myelodysplastic syndromes. Br J Haematol 2009; 146:86.
  67. Gatto S, Ball G, Onida F, et al. Contribution of beta-2 microglobulin levels to the prognostic stratification of survival in patients with myelodysplastic syndrome (MDS). Blood 2003; 102:1622.
  68. Shih LY, Lin TL, Wang PN, et al. Internal tandem duplication of fms-like tyrosine kinase 3 is associated with poor outcome in patients with myelodysplastic syndrome. Cancer 2004; 101:989.
  69. Georgiou G, Karali V, Zouvelou C, et al. Serial determination of FLT3 mutations in myelodysplastic syndrome patients at diagnosis, follow up or acute myeloid leukaemia transformation: incidence and their prognostic significance. Br J Haematol 2006; 134:302.
  70. Bejar R, Stevenson KE, Caughey BA, et al. Validation of a prognostic model and the impact of mutations in patients with lower-risk myelodysplastic syndromes. J Clin Oncol 2012; 30:3376.
  71. Damm F, Chesnais V, Nagata Y, et al. BCOR and BCORL1 mutations in myelodysplastic syndromes and related disorders. Blood 2013; 122:3169.
  72. Bejar R, Stevenson KE, Caughey B, et al. Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation. J Clin Oncol 2014; 32:2691.
  73. Kantarjian H, O'Brien S, Ravandi F, et al. The heterogeneous prognosis of patients with myelodysplastic syndrome and chromosome 5 abnormalities: how does it relate to the original lenalidomide experience in MDS? Cancer 2009; 115:5202.
  74. Tsimberidou AM, Estey E, Wen S, et al. The prognostic significance of cytokine levels in newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndromes. Cancer 2008; 113:1605.
  75. Parnes A, Nikiforow S, Berliner N, Vanasse GJ. Single nucleotide polymorphisms in the human TNF gene are associated with anaemia and neutropenia in a cohort of patients with de novo myelodysplastic syndrome. Br J Haematol 2010; 150:700.
  76. Bowles KM, Warner BA, Baglin TP. Platelet mass has prognostic value in patients with myelodysplastic syndromes. Br J Haematol 2006; 135:198.
  77. Germing U, Platzbecker U, Giagounidis A, Aul C. Platelet morphology, platelet mass, platelet count and prognosis in patients with myelodysplastic syndromes. Br J Haematol 2007; 138:399.
  78. Palmer SR, Tefferi A, Hanson CA, Steensma DP. Platelet count is an IPSS-independent risk factor predicting survival in refractory anaemia with ringed sideroblasts. Br J Haematol 2008; 140:722.
  79. Buesche G, Teoman H, Wilczak W, et al. Marrow fibrosis predicts early fatal marrow failure in patients with myelodysplastic syndromes. Leukemia 2008; 22:313.
  80. Thiele J, Kvasnicka HM, Facchetti F, et al. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica 2005; 90:1128.
  81. Della Porta MG, Malcovati L, Rigolin GM, et al. Immunophenotypic, cytogenetic and functional characterization of circulating endothelial cells in myelodysplastic syndromes. Leukemia 2008; 22:530.