Myelodysplastic syndromes: Contemporary review and how we treat

American Journal of Hematology

Volumn 91, Issue 1, 2016, Pages 76-89

  Gangat, Naseema ^a   Patnaik, Mrinal M ^a   Tefferi, Ayalew ^a  

^a MAYO CLINIC ROCHESTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AZACITIDINE; CYCLOSPORIN; DANAZOL; DECITABINE; DEFERASIROX; ELTROMBOPAG; ENZYME INHIBITOR; GSK 2879552; IMETELSTAT; LENALIDOMIDE; LUSPATERCEPT; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; PINOMETOSTAT; ROMIPLOSTIM; SOTATERCEPT; TAZEMETOSTAT; THYMOCYTE ANTIBODY; UNCLASSIFIED DRUG; ANTINEOPLASTIC ANTIMETABOLITE;

ALLOGENEIC STEM CELL TRANSPLANTATION; ANEMIA; ARTICLE; CYTOGENETICS; DISEASE CLASSIFICATION; DISEASE COURSE; EPIGENETICS; GENETIC SCREENING; HUMAN; INTERMEDIATE RISK PATIENT; INTERNATIONAL PROGNOSTIC SCORING SYSTEM; IRON CHELATION; IRON OVERLOAD; LOW RISK PATIENT; MOLECULAR GENETICS; MOLECULAR PATHOLOGY; MYELODYSPLASTIC SYNDROME; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROGNOSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); THROMBOCYTOPENIA; ANALOGS AND DERIVATIVES; DISEASE FREE SURVIVAL; GENETICS; MORTALITY; MYELODYSPLASTIC SYNDROMES; STEM CELL TRANSPLANTATION;

ANTIMETABOLITES, ANTINEOPLASTIC; AZACITIDINE; DISEASE-FREE SURVIVAL; HUMANS; MYELODYSPLASTIC SYNDROMES; STEM CELL TRANSPLANTATION;

EID: 84954286325     PISSN: 03618609     EISSN: 10968652     Source Type: Journal    
DOI: 10.1002/ajh.24253     Document Type: Article

References (91)

1. 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;114:937-951.
2. Sekeres MA. The epidemiology of myelodysplastic syndromes. Hematol Oncol Clin North Am 2010;24:287-294.
3. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012;120:2454-2465.
4. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997;89:2079-2088.
5. 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;25:3503-3510.
6. 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;113:1351-1361.
7. Patnaik MM, Hanson CA, Hodnefield JM, et al. Differential prognostic effect of IDH1 versus IDH2 mutations in myelodysplastic syndromes: a Mayo Clinic study of 277 patients. Leukemia 2012;26:101-105.
8. Patnaik MM, Lasho TL, Hodnefield JM, et al. SF3B1 mutations are prevalent in myelodysplastic syndromes with ring sideroblasts but do not hold independent prognostic value. Blood 2012;119:569-572.
9. Walter MJ, Ding L, Shen D, et al. Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia 2011;25:1153-1158.
10. Yoshida K, Sanada M, Shiraishi Y, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 2011;478:64-69.
11. Bejar R, Stevenson K, Abdel-Wahab O, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med 2011;364:2496-2506.
12. 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;30:3376-3382.
13. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, 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.
14. Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 2006;106:1794-1803.
15. List A, Kurtin S, Roe DJ, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 2005;352:549-557.
16. Papaemmanuil E, Gerstung M, Malcovati L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood 2013;122:3616-3627.
17. Butturini A, Gale RP, Verlander PC, et al. Hematologic abnormalities in Fanconi anemia: an International Fanconi Anemia Registry study. Blood 1994;84:1650
18. Dokal I. Dyskeratosis congenita in all its forms. Br J Haematol 2000;110:768-779.
19. Vyas P, Roberts I. Down myeloid disorders: a paradigm for childhood preleukaemia and leukaemia and insights into normal megakaryopoiesis. Early Hum Dev 2006;82:767-773.
20. Preudhomme C, Renneville A, Bourdon V, et al. High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder. Blood 2009;113:5583-5587.
21. Bennett JM, Orazi A. Diagnostic criteria to distinguish hypocellular acute myeloid leukemia from hypocellular myelodysplastic syndromes and aplastic anemia: recommendations for a standardized approach. Haematologica 2009;94:264-268.
22. Font P, Loscertales J, Benavente C, et al. Inter-observer variance with the diagnosis of myelodysplastic syndromes (MDS) following the 2008 WHO classification. Ann Hematol 2013;92:19-24.
23. Ohba R, Furuyama K, Yoshida K, et al. Clinical and genetic characteristics of congenital sideroblastic anemia: comparison with myelodysplastic syndrome with ring sideroblast (MDS-RS). Ann Hematol 2013;92:1-9.
24. Kim M, Lee SE, Park J, et al. Vitamin B(12)-responsive pancytopenia mimicking myelodysplastic syndrome. Acta Haematol 2011;125:198-201.
25. Halfdanarson TR, Walker JA, Litzow MR, et al. Severe vitamin B12 deficiency resulting in pancytopenia, splenomegaly and leukoerythroblastosis. Eur J Haematol 2008;80:448-451.
26. Halfdanarson TR, Kumar N, Li CY, et al. Hematological manifestations of copper deficiency: a retrospective review. Eur J Haematol 2008;80:523-531.
27. Parmentier S, Schetelig J, Lorenz K, et al. Assessment of dysplastic hematopoiesis: lessons from healthy bone marrow donors. Haematologica 2012;97:723-730.
28. Matsuda A, Germing U, Jinnai I, et al. Improvement of criteria for refractory cytopenia with multilineage dysplasia according to the WHO classification based on prognostic significance of morphological features in patients with refractory anemia according to the FAB classification. Leukemia 2007;21:678-686.
29. Hasserjian RP, Zuo Z, Garcia C, et al. Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification. Blood 2010;115:1985-1992.
30. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982;51:189-199.
31. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002;100:2292-2302.
32. Papaemmanuil E, Cazzola M, Boultwood J, et al. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med 2011;365:1384-1395.
33. Visconte V, Rogers HJ, Singh J, et al. SF3B1 haploinsufficiency leads to formation of ring sideroblasts in myelodysplastic syndromes. Blood 2012;120:3173-3186.
34. Patnaik MM, Hanson CA, Sulai NH, et al. Prognostic irrelevance of ring sideroblast percentage in World Health Organization-defined myelodysplastic syndromes without excess blasts. Blood 2012;119:5674-5677.
35. Van den Berghe H, Cassiman JJ, David G, et al. Distinct haematological disorder with deletion of long arm of no. 5 chromosome. Nature 1974;251:437-438.
36. Mallo M, Cervera J, Schanz J, et al. Impact of adjunct cytogenetic abnormalities for prognostic stratification in patients with myelodysplastic syndrome and deletion 5q. Leukemia 2011;25:110-120.
37. Jadersten M, Saft L, Smith A, et al. TP53 mutations in low-risk myelodysplastic syndromes with del(5q) predict disease progression. J Clin Oncol 2011;29:1971-1979.
38. Germing U, Lauseker M, Hildebrandt B, et al. Survival, prognostic factors and rates of leukemic transformation in 381 untreated patients with MDS and del(5q): a multicenter study. Leukemia 2012;26:1286-1292.
39. Tang G, Jorgensen LJ, Zhou Y, et al. Multi-color CD34(+) progenitor-focused flow cytometric assay in evaluation of myelodysplastic syndromes in patients with post cancer therapy cytopenia. Leuk Res 2012;36:974-981.
40. Kern W, Haferlach C, Schnittger S, et al. Serial assessment of suspected myelodysplastic syndromes: significance of flow cytometric findings validated by cytomorphology, cytogenetics, and molecular genetics. Haematologica 2013;98:201-207.
41. Jevremovic D, Timm MM, Reichard KK, et al. Loss of blast heterogeneity in myelodysplastic syndrome and other chronic myeloid neoplasms. Am J Clin Pathol 2014;142:292-298.
42. Kwok B, Hall JM, Witte JS, et al. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance. Blood 2015;126:2355-2361.
43. Porwit A, van de Loosdrecht AA, Bettelheim P, et al. Revisiting guidelines for integration of flow cytometry results in the WHO classification of myelodysplastic syndromes-proposal from the International/European LeukemiaNet Working Group for Flow Cytometry in MDS. Leukemia 2014;28:1793-1798.
44. Schanz J, Tuchler H, Sole 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;30:820-829.
45. Gangat N, Patnaik M, Begna KH, et al. Primary myelodysplastic syndromes: The Mayo Clinic Experience with 1000 patients. Mayo Clinic Proc, in press.
46. Wassie E, Finke C, Gangat N, et al. A compendium of cytogenetic abnormalities in myelofibrosis: molecular and phenotypic correlates in 826 patients. Br J Haematol 2015;169:71-76.
47. Wiktor A, Rybicki BA, Piao ZS, et al. Clinical significance of Y chromosome loss in hematologic disease. Genes Chromosomes Cancer 2000;27:11-16.
48. Ebert BL, Pretz J, Bosco J, et al. Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature 2008;451:335-339.
49. Starczynowski DT, Kuchenbauer F, Argiropoulos B, et al. Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype. Nat Med 2010;16:49-58.
50. Abdel-Wahab O, Levine RL. Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia. Blood 2013;121:3563-3572.
51. Thol F, Friesen I, Damm F, et al. Prognostic significance of ASXL1 mutations in patients with myelodysplastic syndromes. J Clin Oncol 2011;29:2499-2506.
52. Soriano AO, Yang H, Faderl S, et al. Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome. Blood 2007;110:2302-2308.
53. Ko M, Huang Y, Jankowska AM, et al. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature 2010;468:839-843.
54. Figueroa ME, Abdel-Wahab O, Lu C, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 2010;18:553-567.
55. Itzykson R, Kosmider O, Cluzeau T, et al. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia 2011;25:1147-1152.
56. Traina F, Visconte V, Elson P, et al. Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms. Leukemia 2014;28:78-87.
57. Song SJ, Ito K, Ala U, et al. The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation. Cell Stem Cell 2013;13:87-101.
58. Verburgh E, Achten R, Maes B, et al. Additional prognostic value of bone marrow histology in patients subclassified according to the International Prognostic Scoring System for myelodysplastic syndromes. J Clin Oncol 2003;21:273-282.
59. 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;31:2671-2677.
60. Mishra A, Corrales-Yepez M, Ali NA, et al. Validation of the revised International Prognostic Scoring System in treated patients with myelodysplastic syndromes. Am J Hematol 2013;88:566-570.
61. Garcia-Manero G, Shan J, Faderl S, et al. A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia 2008;22:538-543.
62. Damm F, Chesnais V, Nagata Y, et al. BCOR and BCORL1 mutations in myelodysplastic syndromes and related disorders. Blood 2013;122:3169-3477.
63. Thol F, Kade S, Schlarmann C, et al. Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes. Blood 2012;119:3578-3584.
64. 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;32:2691-2698.
65. Santini V. Clinical use of erythropoietic stimulating agents in myelodysplastic syndromes. Oncologist 2011;16:35-42.
66. Greenberg PL, Sun Z, Miller KB, et al. Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996). Blood 2009;114:2393-2400.
67. Chabannon C, Molina L, Pegourie-Bandelier B, et al. A review of 76 patients with myelodysplastic syndromes treated with danazol. Cancer 1994;73:3073-3780.
68. Letendre L, Levitt R, Pierre RV, et al. Myelodysplastic syndrome treatment with danazol and cis-retinoic acid. Am J Hematol 1995;48:233-236.
69. Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 2006;108:2509-2519.
70. Sloand EM, Wu CO, Greenberg P, et al. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol 2008;26:2505-2511.
71. Aalbers AM, van der Velden VH, Yoshimi A, et al. The clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory cytopenia of childhood: a prospective study by EWOG-MDS. Leukemia 2014;28:189-192.
72. Passweg JR, Giagounidis AA, Simcock M, et al. Immunosuppressive therapy for patients with myelodysplastic syndrome: a prospective randomized multicenter phase III trial comparing antithymocyte globulin plus cyclosporine with best supportive care-SAKK 33/99. J Clin Oncol 2011;29:303-309.
73. Kronke J, Fink EC, Hollenbach PW, et al. Lenalidomide induces ubiquitination and degradation of CK1alpha in del(5q) MDS. Nature 2015;523:183-188.
74. List A, Dewald G, Bennett J, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 2006;355:1456-1465.
75. Komrokji RS, Garcia-Manero, G, Ades L, et al. An open-label, phase 2, dose-finding study of sotatercept (ACE-011) in patients with low or intermediate-1 (Int-1)-risk myelodysplastic syndromes (MDS) or non-proliferative chronic myelomonocytic leukemia (CMML) and anemia requiring transfusion. Blood 2014;124:3251.
76. Platzbecker U, Germing U, Giagounidis A, et al. ACE-536 increases hemoglobin and reduces transfusion burden in patients with low or intermediate-1 risk myelodysplastic syndromes (MDS): preliminary results from a phase 2 study. Blood 2014;124:411.
77. Alessandrino EP, Della Porta MG, Bacigalupo A, et al. Prognostic impact of pre-transplantation transfusion history and secondary iron overload in patients with myelodysplastic syndrome undergoing allogeneic stem cell transplantation: a GITMO study. Haematologica 2010;95:476-484.
78. Neukirchen J, Fox F, Kundgen A, et al. Improved survival in MDS patients receiving iron chelation therapy - a matched pair analysis of 188 patients from the Dusseldorf MDS registry. Leuk Res 2012;36:1067-1070.
79. Chacko J, Pennell DJ, Tanner MA, et al. Myocardial iron loading by magnetic resonance imaging T2* in good prognostic myelodysplastic syndrome patients on long-term blood transfusions. Br J Haematol 2007;138:587-593.
80. Giagounidis A, Mufti GJ, Fenaux P, et al. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1-risk myelodysplastic syndrome and thrombocytopenia. Cancer 2014;120:1838-1846.
81. Natalie Oliva E, Santini V, Gini Z. Efficacy and safety of eltrombopag for the treatment of thrombocytopenia of low and intermediate-1 IPSS risk myelodysplastic syndromes: interim analysis of a prospective, randomized, single-blind, placebo-controlled trial (EQoL-MDS). Blood 2012; 120: (Abstract 923).
82. Townsley D, Desmond R, Weinstein B, et al. Eltrombopag for low to intermediate-2 risk myelodysplastic syndrome. Leuk Res 2015;39:1s.
83. Voso MT, Breccia M, Lunghi M, et al. Rapid loss of response after withdrawal of treatment with azacitidine: a case series in patients with higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia. Eur J Haematol 2013;90:345-348.
84. Silverman LR, Fenaux P, Mufti GJ, et al. Continued azacitidine therapy beyond time of first response improves quality of response in patients with higher-risk myelodysplastic syndromes. Cancer 2011;117:2697-2702.
85. Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol 2002;20:2429-2440.
86. Steensma DP, Baer MR, Slack JL, et al. Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. J Clin Oncol 2009;27:3842-3848.
87. Lubbert M, Suciu S, Baila L, et al. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol 2011;29:1987-1996.
88. Garcia-Manero G, Kantarjian HM, Sanchez-Gonzalez BY, et al. Phase 1/2 study of the combination of 5-aza-2′-deoxycytidine with valproic acid in patients with leukemia. Blood 2006;108:3271-3279.
89. Prebet T, Gore SD, Esterni B, et al. Outcome of high-risk myelodysplastic syndrome after azacitidine treatment failure. J Clin Oncol 2011;29:3322-3327.
90. Cutler CS, Lee SJ, Greenberg P, et al. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood 2004;104:579-585.
91. Koreth J, Pidala J, Perez WS, et al. Role of reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation in older patients with de novo myelodysplastic syndromes: an international collaborative decision analysis. J Clin Oncol 2013;31:2662-2670.