We searched Medline for articles published from January, 1981, to April, 2013, with the term “myelodysplastic syndrome”. We largely selected publications from the past 5 years, but we did not exclude commonly referenced and highly regarded older publications. We also searched the reference lists of articles identified by this search strategy and selected those that we judged relevant. Several review articles were included because they provide comprehensive overviews that are beyond the scope of
SeminarMyelodysplastic syndromes
Introduction
Myelodysplastic syndromes are clonal stem-cell disorders predominantly occurring in elderly people. The pathophysiology is a multistep process involving cytogenetic changes, gene mutations, or both,1 with widespread gene hypermethylation at advanced stages.2, 3, 4 The syndromes are characterised by ineffective haemopoiesis leading to blood cytopenias and by progression to acute myeloid leukaemia in a third of patients.5
Diagnosis of myelodysplastic syndromes is still based on examination of the blood and bone marrow, which shows blood cytopenias and hypercellular marrow with dysplasia, with or without excess of marrow immature cells (blasts).6 Prognosis depends mainly on the marrow blast percentage, number and extent of cytopenias, and cytogenetic abnormalities.7, 8 Treatment, varying from symptomatic treatment of cytopenias, especially by transfusions, to allogeneic stem-cell transplantation, has improved in the past few years.
Section snippets
Incidence and cause
Myelodysplastic syndromes are generally diseases of older people, with a median age at diagnosis of 65–70 years; less than 10% of the patients are younger than 50 years. The disorder shows a slight male predominance except for in the form with isolated 5q deletion in which women predominate.9 The annual incidence of myelodysplastic syndromes is about four cases per 100 000 people (reaching 40–50 per 100 000 after age 70 years).9 There are no known ethnic differences in the incidence, but in
Ineffective haemopoiesis
Ineffective haemopoiesis in myelodysplastic syndromes results from the increased susceptibility of clonal myeloid progenitors to apoptosis, which leads to cytopenias despite a generally hypercellular marrow (figure).19 Progression to acute myeloid leukaemia is thought to result from a subsequent shift from apoptosis to proliferation of these clonal progenitors.20, 21 In many cases expansion is oligoclonal, rather than monoclonal; expansion of minor subclones can also contribute to
Clinical findings
Clinical features are non-specific and mainly result from cytopenias, especially anaemia, which is symptomatic in many patients, leading to fatigue, poor quality of life, and destabilisation of underlying cardiovascular disease. Thrombocytopenia is commonly associated with platelet dysfunction, potentially leading to bleeding symptoms even in moderate thrombocytopenia. Similarly, infections (especially with gram-negative bacilli, gram-positive cocci, and fungi) can occur with only moderate
Classification
Morphological classification of myelodysplastic syndromes is based on the WHO 2008 criteria6 (table 3). The best defined categories are refractory anaemia with excess blasts (type 1 or 2 based on the marrow blast count being below or above 10%), refractory anaemia with or without ringed sideroblasts, refractory cytopenias with multilineage dysplasia, and myelodysplastic syndromes with isolated deleted 5q. Categories of refractory cytopenia with unilineage dysplasia other than refractory anaemia
International prognostic scoring system (IPSS) and its update
Many prognostic factors have been identified in myelodysplastic syndromes but international efforts have concentrated on identification of a small number of features with independent prognostic value, routinely available in all centres, which can be grouped in scoring systems. A high percentage of marrow blasts, increasing number and importance of cytopenias, and abnormal karyotype are the most important independent factors of poor prognosis in myelodysplastic syndromes; the IPSS7 allows
Strategy
Treatment of myelodysplastic syndromes has improved lately but remains challenging. The therapeutic strategy remains largely based on the IPSS. In patients classified as high or intermediate 2 on the IPSS (higher risk) with median survival if untreated of only about 12 months, treatment should aim to modify the disease course, avoiding progression to acute myeloid leukaemia, and extending survival. By contrast, in those classified as low or intermediate 1 on the IPSS (lower risk), survival is
Treatment of lower-risk myelodysplastic syndromes
Treatment approaches mainly focus, at least initially, on the treatment of cytopenias. Anaemia is the predominant cytopenia in most patients with lower-risk myelodysplastic syndromes. Chronic anaemia leads to increased morbidity and lower quality of life,126, 127 and many patients need repeated erythrocyte transfusions, which might (although this notion is disputed) result in potentially deleterious iron overload in various organs.126
High-dose erythropoiesis-stimulating agents, including
Search strategy and selection criteria
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