Myelodysplastic syndrome
Myelodysplastic syndrome (MDS) consists of a group of clonal
haematopoietic disorders which represent steps in the progression to
the development of leukaemia. MDS presents with consequences of
bone marrow failure (anaemia, recurrent infections or bleeding), usually
in older people (median age at diagnosis is 69 years).
The blood film is characterised by cytopenias and abnormal-looking
(dysplastic) blood cells, including macrocytic red cells and hypogranular
neutrophils with nuclear hyper- or hyposegmentation. The bone marrow
is hypercellular, with dysplastic changes in all three cell lines. Blast cells
may be increased but do not reach the 20% level that indicates acute
leukaemia. Chromosome analysis frequently reveals abnormalities,
particularly of chromosome 5 or 7.
Inevitably, MDS progresses to AML, although the time to progression
varies (from months to years) with the subtype of MDS, being slowest in
refractory anaemia and most rapid in refractory anaemia with excess of
blasts. An international prognostic scoring system (IPSS) predicts clinical
outcome based upon karyotype and cytopenias in blood, as well as
percentage of bone marrow blasts. In low-risk patients, median survival
is 5.7 years and time for 25% of patients to develop AML is 9.4 years;
equivalent figures in high-risk patients are 0.4 and 0.2 years,
respectively.
WHO classification of myelodysplastic syndromes
Refractory anaemia (RA) Blasts < 5% Erythroid dysplasia only
Refractory anaemia with sideroblasts (RARS) Blasts < 5% Ringed
sideroblasts > 15%
Refractory cytopenias with multilineage dysplasia (RCMD) Blasts < 5%
2–3 lineage dysplasia
Refractory anaemia with excess blasts (RAEB) Blasts 5–20% 2–3 lineage
dysplasia
Myelodysplastic syndrome with 5q− Myelodysplastic syndrome
associated with a del (5q) cytogenetic abnormality Blasts < 5% Often
normal or increased blood platelet count
Myelodysplastic syndrome Unclassified None of the above or
inadequate material
Management
For the vast majority of patients who are elderly, the disease is
incurable, and supportive care with red cell and platelet transfusions is
the mainstay of treatment. A trial of erythropoietin and granulocyte–
colony-stimulating factor (G–CSF) is recommended in some patients with
early disease to improve haemoglobin and white cell counts. For
younger patients with higher-risk disease, allogeneic HSCT may afford a
cure. Transplantation should be preceded by intensive chemotherapy in
those with more advanced disease. More recently, the hypomethylating
agent azacytidine has improved survival by a median of 9 months for
high-risk patients,