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  • Print publication year: 2010
  • Online publication date: January 2011

6 - Myelodysplastic syndromes (MDS)

Summary

Introduction

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders which are distinguished by cytopenias in the face of hypercellular marrows and dysplastic hematopoietic cell lines. Up into the 1970s MDS have been called “preleukemia” expressing the proximity of MDS to acute myeloid leukemia (AML), and their capacity to evolve into AML over time. Although MDS is the currently accepted term, the pathophysiology of MDS varies widely extending from abnormalities of apoptosis and differentiation to proliferation and maturation arrest. It is nowadays also better understood that there are notable differences between MDS and AML, a separation which is also underlined by the clinical manifestations and prognosis of MDS, which are primarily determined by cytopenias and not leukemic transformation. The complexity of pathophysiology and resultant heterogeneity of prognosis have led to several recent attempts to fine tune criteria for diagnosis and classification. In addition, recent years have also seen important advances of treatment with respect to hematopoietic growth factors, iron chelation, and particularly epigenetic therapy and immunomodulatory inhibitory derivatives (e.g., lenalidomide). These developments have made the care of patients with MDS more demanding but at the same time more satisfying as the possibilities for patients with MDS are now larger than before.

References
Heaney, M, Golde, D. Myelodysplasia. New Engl J Med 1999;340:1649–60.
Albitar, M, Manshouri, T, Shen, Y, et al. Myelodysplastic syndrome is not merely “preleukemia.”Blood 2002;100:791–8.
Kuendgen, A, Strupp, C, Avivado, M, et al. Myelodysplastic syndromes in patients younger than age 50. J Clin Oncol 2006;24:5358–65.
Rollison, , Hayat, M, Smith, M, et al. First report of national estimates of the incidence of myelodysplastic syndromes and chronic myeloproliferative disorders from the U.S. SEER Program. Blood 2006;108:77a.
Goldberg, SL, Mody-Patel, N, Chen, ER. Clinical and economic consequences of myelodysplastic syndromes in the United States: an analysis of the Medicare database. Blood 2008;112:237.
Nagata, C, Shimizu, H, Hirashima, K, et al. Hair dye use and occupational exposure to organic solvents as risk factors for myelodysplastic syndrome. Leuk Res 1999;23:57–62.
Kimura, A, Takeuchi, Y, Tanaka, H, et al. Atomic bomb radiation increases the risk of MDS. Leuk Res 2001;25:S13.
Park, DJ, Koeffler, HP. Therapy-related myelodysplastic syndromes. Semin Hematol 1996;33:256–73.
Armitage, JO, Carbone, PP, Connors, JM, et al. Treatment-related myelodysplasia and acute leukemia in non-Hodgkin's lymphoma patients. J Clin Oncol 2003;21:897–906.
Bowen, D, Culligan, D, Jowitt S, et al. of the UK MDS Guidelines Group. Guidelines for the diagnosis and therapy of adult myelodysplastic syndromes. Br J Haematol 2003;120:187–200.
Rosenfeld, C, List, A. A hypothesis for the pathogenesis of myelodysplastic syndromes: implications for new therapies. Leukemia 2000;14:2–8.
Testa, LJ. Apoptotic mechanisms in the control of erythropoiesis. Leukemia 2004;18:1176–99.
Parker, JE, Mufti, GJ, Rasool, F, et al. The role of apoptosis, proliferation, and the BCL2-related proteins in the myelodysplastic syndromes and acute myeloid leukemia secondary to MDS. Blood 2000;96:3932–8.
Campioni, D, Secchiero, P, Corallini, F, et al. Evidence for a role of TNF-related apoptosis-inducing ligand (TRAIL) in the anemia of myelodysplastic syndromes. Am J Pathol 2005;166:557–63.
Bruce Galili, N, Mehdi, M, Mumtaz, J, et al. Can molecular profiling of cytogenetic subgroups draw a roadmap for individualizing therapy in myelodysplastic syndromes?Future Oncol 2006;2:407–15.
Haase, D, Steidl, D, Schanz, J, et al. Correlation of cytogenetic findings with morphology, clinical course, and prognosis in 2124 patients with MDS. Blood 2005;106:232a.
Haase, D, Germing, U, Schanz, J, 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;110:4385–95.
Vardiman, JW, Harris, NL, Brunning, RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002;100:2292–302.
Ebert, B, Pretz, J, Bosco, J, et al. Identification of RPS14 as a 5q- syndrome gene by RNA interference screen. Nature 2008;451:335–9.
Hirai, H, Kobayashi, Y, Mano, H, et al. A point mutation at codon 13 of the N-ras oncogene in myelodysplastic syndrome. Nature 1987;327:430–32.
Liu, E, Hjelle, B, Morgan, R, et al. Mutations of the Kirsten-ras proto-oncogene in human preleukaemia. Nature 1987;330:186–8.
Wu, S-J, Chou, W-C, Yao, M, et al. SOCS1 methylation predicts a high risk of acute leukemic transformation in primary myelodysplastic syndrome. Blood 2006;108:742a.
Bennett, JM, Catovsky, D, Daniel, MT, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982;51:189–99.
Verhoef, GEG, Pittaluga, S, Wolfe-Peters, CDE, et al. FAB classification of myelodysplastic syndromes: merits and controversies. Ann Hematol 1995;71:3–11.
Germing, U, Strupp, C, Kuendgen, A, et al. Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes. Haematologica 2006;91:1596–604.
Greenberg, P, Cox, C, LeBeau, MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997;89:2079–88.
Estey, E, Keating, M, Pierce, S, et al. Application of the international scoring system for myelodysplasia to MD Anderson patients. Blood 1997;90:2843–4.
Cazzola, M, Malcovati, L. Myelodysplastic syndromes: coping with ineffective hematopoiesis. N Engl J Med 2005;352:536–8.
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;113:1351–61.
Wong, KF, So, CC. Hyoplastic myelodysplastic syndrome – a clinical, morphologic, or genetic diagnosis?Cancer Genet Cytogenet 2002;138:85–8.
Matsui, WH, Brodksy, RA, Smith, BD, et al. Quantitative analysis of bone marrow CD34 cells in aplastic anemia and hypoplastic myelodysplastic syndromes. Leukemia 2006;20:458–62.
Della Porta, MG, Malcovati, L, Boveri, E, et al. Clinical clusters of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes. J Clin Oncol 2009;27:754–62.
Bowen, DT. Chronic myelomonocytic leukemia: lost in classification?Hematol Oncol 2005;23:26–33.
Remacha, AF, Nomdedéu, JF, Puget, G, et al. Occurrence of the JAK2 V617F mutation in the WHO provisional entity: myelodysplastic/myeloproliferative disease, unclassifiable-refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Haematologica 2006;91:719–20.
David, M, Cross, NCP, Burgstaller, S, et al. Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders. Blood 2007;109:61–4.
Cheson, BD, Bennett, JM, Kantarjian, HM, et al. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 2000;96:3671–4.
Cheson, BD, Greenberg, PL, Bennett, JM, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 2006;108:419–25.
Gattermann, N, Schmid, M, Della Porta, M, et al. Efficacy and safety of Deferasirox (Exjade®) during 1 year of treatment in transfusion-dependent patients with myelodysplastic syndromes: results from EPIC trial. Blood 2008;112:235.
List, AF, Baer, MR, Steensma, D, et al. Iron chelation with Deferasirox (Exjade®) improves iron burden in patients with myelodysplastic syndromes (MDS). Blood 2008;112:236.
Hellström-Lindberg, E, Gulbrandsen, N, Lindberg, G, et al. A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life. Br J Haematol 2003;120:1037–46.
Park, S, Kelaidi, C, Grabar, S, et al. Prognostic factors and response duration in 419 MDS treated with erythropoietin ± G-CSF: The GFM experience. Blood 2006;108:158a.
Jädersten, M, Montgomery, SM, Dybedal, I, et al. Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood 2005;106:803–11.
Kantarjian, HM, Giles, F, List, AF, et al. The incidence and impact of thrombocytopenia in myelodysplastic syndrome (MDS). Blood 2006;108:739a.
Montero, AJ, Estrov, Z, Freireich, EJ, et al. Phase II study of low-dose interleukin-11 in patients with myelodysplastic syndrome. Leuk Lymphoma 2006;47:2049–54.
Bussel, JB, Cheng, G, Saleh, MN, et al. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med 2007;357:2237–47.
Bussel, JB, Kuter, DJ, George, JN, et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med 2006;355:2054.
Kantarjian, H, Fenaux, P, Sekeres, MA, et al. Phase 1/2 study of AMG 531 in thrombocytopenic patients (Pts) with low-risk myelodysplastic syndrome (MDS): update including extended treatment. Blood 2007;110:81a.
Molldrem, JJ, Leifer, E, Bahceci, E, et al. Antithymocyte globulin for treatment of the bone marrow failure associated with myelodysplastic syndromes. Ann Intern Med 2002;137:156–63.
Stadler, M, Germing, U, Kliche, K-O, et al. A prospective, randomized, phase II study of horse antithymocyte globulin vs rabbit antithymoycte globulin as immune-modulating therapy in patients with low-risk myelodysplastic syndrome. Leukemia 2004;18:460–5.
Lim, Z, Killick, S, Cavenagh, J, et al. European multi-centre study on the use of anti-thymocyte globulin in the treatment of myelodysplastic syndromes. Blood 2005;106:707a.
Sloand, EM, Wu, C, Greenberg, P, et al. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol 2008;26:2505–11.
Paquette, RL, Tebyani, N, Frane, M, et al. Long-term outcome of aplastic anemia in adults treated with antithymocyte globulin: comparison with bone marrow transplantation. Blood 1995;85:283–90.
List, A, Kurtin, S, Roe, DJ, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 2005;352:549–57.
List, A, Dewald, G, Bennett, J, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 2006;355:1456–65.
Raza, A, Reeves, JA, Feldman, EJ, et al. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood 2008;111:86–93.
Issa, J-P. Optimizing therapy with methylation inhibitors in myelodysplastic syndromes: dose, duration, and patient selection. Nat Clin Pract Oncol 2005;2 Suppl 1:S24–9.
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;20:2429–40.
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 randomized, open-label, phase III study. Lancet Oncol 2009;10:223–32.
Wijermans, P, Lübbert, M, Verhoef, G, et al. An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2'-deoxycytidine (decitabine) in 177 patients. Ann Hematol 2005;84:9–17.
Kantarjian, H, Issa, J-P, Rosenfeld, CS, et al. Decitabine improves patient outcome in myelodysplastic syndrome. Cancer 2006;106:1794–803.
Kantarjian, H, Oki, Y, Garcia-Manero, G, et al. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 2007;109:52–7.
Steensma, DP, Baer, MR, Slack, JL, et al. Preliminary results of a phase II study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndrome (MDS). Blood 2007;110:434a.
Wijermans, P, Suciu, S, Baila, L, et al. Low dose decitabine versus best supportive care in elderly patients with intermediate or high risk MDS not eligible for intensive chemotherapy: final results of the randomized phase III study (06011) of the EORTC leukemia and German MDS Study Groups. Blood 2008;112:90.
Silverman, LR, McKenzie, DR, Peterson, BL, et al. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol 2006;24:3895–902.
Borthakur, G, Ahdab, SE, Ravandi, F, et al. Activity of decitabine in patients with myelodysplastic syndrome previously treated with azacitdine. Leuk Lymphoma 2008;49:650–1.
Vey, N, Bosly, A, Guerci, A, et al. Arsenic trioxide in patients with myelodysplastic syndromes: a phase II multicenter study. J Clin Oncol 2006;24:2465–72.
Schiller, GJ, Slack, J, Hainsworth, JD, et al. Phase II multicenter study of arsenic trioxide in patients with myelodysplastic syndromes. J Clin Oncol 2006;24:2456–64.
Cain, JA, Grisolano, JL, Laird, AD, et al. Complete remission of TEL-PDGFRB-induced myeloproliferative disease in mice by receptor tyrosine kinase inhibitor SU11657. Blood 2004;104:561–4.
Raza, A, Callander, N, Ochoa, L, et al. Hematologic improvement (HI) by TLK199 (Telintra™), a novel glutathione analog, in myelodysplastic syndrome: phase 2 study results. Blood 2005;106:708a.
Borthakur, G, O'Brien, S, Ravandi-Kashani, F, et al. A phase I trial of the small molecule pan-BCL2 family inhibitor Obatoclax (GX15–070) administered by 24 hour infusion every 2 weeks to patients with myeloid malignancies and chronic lymphocytic leukemia (CLL). Blood 2006;108:750a.
Faderl, S, Garcia-Manero, G, Ravandi, F, et al. Oral (po) and intravenous (iv) clofarabine for patients (pts) with myelodysplastic syndrome (MDS). Blood 2008;112:89.
Jabbour, E, Kantarjian, HM, Cortes, J, et al. Survival benefit with decitabine compared to historical experience with intensive chemotherapy in patients with high risk myelodysplastic syndrome (MDS). Blood 2006;108:749a.
Beran, M, Shen, Y, Kantarjian, H, et al. High-dose chemotherapy in high-risk myelodysplastic syndrome – covariate-adjusted comparison of five regimens. Cancer 2001;92:1999–2015.
Deeg, HJ, Appelbaum, FR. Hematopoietic stem cell transplantation in patients with myelodysplastic syndrome. Leuk Res 2000;24:653–63.
Sierra, J, Perez, WS, Rozman, C, et al. Bone marrow transplantation from HLA-identical siblings as treatment for myelodsyplasia. Blood 2002;200:1997–2004.
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;104:579–85.
Martino, R, Iacobelli, S, Brand, R, et al. Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes. Blood 2006;108:836–46.
Deeg, HJ, Storer, B, Slattery, JT, et al. Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome. Blood 2002;100:1201–7.