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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Biol Blood Marrow Transplant. Author manuscript; available in PMC 2011 January 1.
Published in final edited form as:
PMCID: PMC2832713

Myelodysplastic Syndromes: From Neglect to Prominence

Bone marrow disorders that would qualify as what we now call myelodysplastic syndromes (MDS) have been recognized for at least a century [1]. However, it was not until the 1970s and early 1980s that Bennett et al. presented a classification system [2]. This French-American-British (FAB) classification proved to be very helpful for clinical prognostication and treatment decisions. The more recent development of the International Prognostic Scoring System (IPSS) by Greenberg, et al. [3], and the subsequent proposal by the World Health Organization [4,5] reflect our improving understanding of various parameters that impact the disease course. The addition of red blood cell transfusion dependence to the WHO scoring system in the WPSS may have further improved our ability to predict patient risk and prognosis [6].

The recognition as a clonal disorder of hematopoietic stem/precursor cells identified MDS as a disease that should be treatable and potentially curable by hematopoietic cell transplantation (HCT) [7]. This proved indeed to be the case, and by now some patients have been followed for more than 25 years, apparently cured of their disease [8]. However, this modality of treatment has been applied only to a small proportion of patients, either because of concerns about the toxicity associated with HCT in patients who might have a life expectancy of several years with conservative management; because of age, a most relevant factor since the median age at diagnosis of MDS is in the eighth decade of life; or because of the lack of a suitable donor [9,10]. Various developments in the field of HCT, however, have expanded the indications for transplantation and have reduced the morbidity and toxicity associated with the procedure [11-13].

Concurrently, studies aimed at characterizing at the cellular and molecular levels the pathophysiology of MDS have resulted in new insights and the development of non-transplant therapies. The FDA approval of three drugs (5 azacitidine; 5 aza-2′deoxyazacitidine; lenalidomide) for the treatment of MDS over the past few years has led to extensive studies on the indications, efficacy and limitations of these drugs [14-18]. Other modalities of treatment such as immunosuppression or cytokine blockade have shown promise in subgroups of patients [19-22]. Those studies, in turn, have stimulated interest in further defining various aspects of the pathogenesis and pathophysiology of MDS.

At the same time, a proportion of patients who are being treated successfully with chemotherapy or radiation for various diagnoses has been found to develop MDS, apparently secondary to the effects of cytotoxic therapy [23-25]. These treatment-related cases of MDS tend to behave more aggressively and generally are more difficult to treat than de novo MDS.

In this symposium, three experts are providing an update on transplant and non-transplant therapy for MDS and our current understanding of secondary MDS.


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1. The Myelodysplatic Syndromes: Pathobiology and Clinical Management. New York, NY: Marcel Dekker, Inc.; 2002.
2. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982;51:189–199. [PubMed]
3. Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079–2088. erratum appears in Blood 1998 Feb 1;91(3):1100. [PubMed]
4. Harris NL, Jaffe ES, Diebold J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the clinical advisory committee meeting - Airlie House, Virginia, November 1997. J Clin Oncol. 1999;17:3835–3849. [PubMed]
5. 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. [PubMed]
6. 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. [PubMed]
7. Appelbaum FR, Storb R, Ramberg RE, et al. Allogeneic marrow transplantation in the treatment of preleukemia. Ann Intern Med. 1984;100:689–693. [PubMed]
8. Deeg HJ. Hematopoietic cell transplantation for myelodysplastic syndrome and myeloproliferative disorders. In: Appelbaum FR, Forman SJ, Negrin RS, Blume KG, editors. Thomas' Hematopoietic Cell Transplantation. Oxford, UK: Wiley-Blackwell; 2009. pp. 827–844.
9. Oosterveld M, Suciu S, Verhoef G, et al. The presence of an HLA-identical sibling donor has no impact on outcome of patients with high-risk MDS or secondary AML (sAML) treated with intensive chemotherapy followed by transplantation: results of a prospective study of the EORTC, EBMT, SAKK and GIMEMA Leukemia Groups (EORTC study 06921) Leukemia. 2003;17:859–868. [PubMed]
10. de Lima M, Couriel D, Shahjahan M, et al. Allogeneic transplantation for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) using a low-toxicity combination of intravenous (IV) busulfan (Bu) and fludarabine (Flu) ± ATG. Blood. 2002;100(Part 1):853a. #3366[abstr.]
11. 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;108:836–846. [PubMed]
12. Ho AYL, Pagliuca A, Kenyon M, et al. Reduced-intensity allogeneic hematopoietic stem cell transplantation for myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using fludarabine, busulphan and alemtuzumab (FBC) conditioning. Blood. 2004;104:1616–1623. [PubMed]
13. Scott BL, Sandmaier BM, Storer B, et al. Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia. 2006;20:128–135. [PubMed]
14. 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. [PubMed]
15. 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. [PMC free article] [PubMed]
16. Wijermans PW, Krulder JW, Huijgens PC, Neve P. Continuous infusion of low-dose 5-Aza-2′-deoxycytidine in elderly patients with high-risk myelodysplastic syndrome. Leukemia. 1997;11:1–5. [PubMed]
17. Lubbert M, Wijermans P, Kunzmann R, et al. Cytogenetic responses in high-risk myelodysplastic syndrome following low-dose treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine. Br J Haematol. 2001;114:349–357. [PubMed]
18. 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;109:52–57. [PubMed]
19. Molldrem JJ, Leifer E, Bahceci E, et al. Antithymocyte globulin for treatment of the bone marrow failure associated with myelodysplastic syndrome. Ann Intern Med. 2002;137:156–163. summary for patients in Ann Intern Med. 2002 Aug 6;137(3):I-27. [PubMed]
20. Sloand EM, Wu CO, Greenberg P, Young N, Barrett J. Factors affecting response and survival in patients with myelodysplasia treated with immunosupporessive therapy. J Clin Oncol. 2008;26:2505–2511. [PubMed]
21. Killick SB, Mufti G, Cavenagh JD, et al. A pilot study of antithymocyte globulin (ATG) in the treatment of patients with ‘low-risk’ myelodysplasia. Br J Haematol. 2003;120:679–684. [PubMed]
22. Deeg HJ, Jiang PYZ, Holmberg LA, Scott B, Petersdorf EW, Appelbaum FR. Hematologic responses of patients with MDS to antithymocyte globulin plus etanercept correlate with improved flow scores of marrow cells. Leuk Res. 2004;28:1177–1180. [PubMed]
23. Neglia JP, Friedman DL, Yasui Y, et al. Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study. J Natl Cancer Inst. 2001;93:618–629. [PubMed]
24. Metayer C, Curtis RE, Vose J, et al. Myelodysplastic syndrome and acute myeloid leukemia after autotransplantation for lymphoma: a multicenter case-control study. Blood. 2003;101:2015–2023. [PubMed]
25. Witherspoon RP, Deeg HJ, Storer B, Anasetti C, Storb R, Appelbaum FR. Hematopoietic stem-cell transplantation for treatment-related leukemia or myelodysplasia. J Clin Oncol. 2001;19:2134–2141. [PubMed]