Pathogenesis, classification, and treatment of myelodysplastic syndromes (MDS)

Abstract

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal myeloid disorders characterized by morphologic dysplasia in one or more cell lineages. Dysplasia in MDS is associated with insufficient production of blood cells and consecutive cytopenia(s). The natural course and prognosis of MDS vary among patients and depend on genetic defects that occur during clonal evolution. In a significant group of patients (roughly 30%) progression to secondary leukemia is observed. These patients appear to have a grave prognosis. The treatment of patients with MDS has to be adjusted to the individual situation and age in each case. In many patients, control of blast cell production by palliative cytoreduction, continuous support with red blood cells, as well as other supportive measures, seem appropriate. In other patients, however, curative therapy (chemotherapy, stem cell transplantation) should be considered. The final decision to offer curative therapy must be based on many different factors including age and the overall situation of the patient. Recently established scoring systems aimed at predicting survival and evolution of leukemia in MDS may be helpful in this regard.

Differentiation and hematopoietic-support of clonal cells in myelodysplastic syndromes

“…The pathophysiology of myelodysplastic syndromes (MDS) is still not completely understood [1]. Some patients with MDS remain clinically stable for extended periods while most AML cases show rapid expansion of malignant clonal cells.…”

Iron overload in myelodysplastic syndromes (MDS) – diagnosis, management, and response criteria: a proposal of the Austrian MDS platform

“…Myelodysplastic syndromes (MDS) are a heterogeneous group of myeloid neoplasms defined by abnormal differentiation and maturation of myeloid cells, bone marrow failure, and a genetic instability with an enhanced risk of transformation to secondary leukaemia [1][2][3][4][5]. Most patients with MDS present with transfusion-dependent anaemia with or without additional cytopenias [1][2][3][4].…”

“…More recently, the World Health Organization (WHO) has worked out an updated classification [8] that represents an extension of the FAB proposal, with several modifications, that include the removal of the subvariant ‘refractory anaemia with excess of blasts in transformation’ (RAEB‐T; now in the group ‘acute myeloid leukaemia’, AML) and of chronic myelomonocytic leukaemia (CMML), recognition of the impact of multilineage dysplasia, and delineation of a cytogenetically defined variant, the 5q‐syndrome [3,4,8]. However, in one particular WHO category, the prognosis and clinical picture may vary among patients depending on deregulated genes and the specific biological properties of the clone(s) [3–6]. Whereas some patients transform to leukaemia or die from complications of bone marrow failure within a short time, other patients survive for many years.…”

“…Whereas some patients transform to leukaemia or die from complications of bone marrow failure within a short time, other patients survive for many years. The International Prognostic Scoring System (IPSS) and other scoring systems (like the Düsseldorf‐score, Toyama‐score, Mufti‐score or Sanz‐score) can assist in prognostication in MDS concerning survival and leukaemia‐free survival [3–5,9]. All these score systems are based on multiple prognostic parameters.…”

Classification, Treatment Goals, and Management Principles for Myelodysplasic Syndromes

“…[6][7][8] To improve prognostic utility, the World Health Organization (WHO) published a new standard classification system. 2,9,10 Regardless of the precision in classifying disease characteristics, a classification system alone does not predict outcomes. While the WHO has added some important cate-…”