The myelodysplastic syndromes (MDS) are a group of biologically and clinically heterogeneous clonal disorders characterised by ineffective haematopoiesis and peripheral cytopenia due to increased apoptosis and by a variable tendency to evolve to acute myeloblastic leukaemia.


Predominantly affects elderly but may occur at any age; median age 69; annual incidence 4/100,000 in general population; rising from 0.5/100,000 aged <50 years to 89/100,000 aged >80 years.

Risk factors

• Prior cancer therapy: notably with radiotherapy, alkylating agents (chlorambucil, cyclophosphamide, melphalan; peak 4-10 years after therapy) or epipodophyllotoxins (etoposide, teniposide; peak within 5 years). Note: prolonged alkylator therapy used in rheumatology and other specialties.

• Environmental toxins: notably benzene and other organic solvents; related to intensity and duration of exposure; also smoking, petroleum products, fertilisers, semi-metal, stone dusts and cereal dusts.

• Genetic: rare familial syndromes; MDS increased in children with Schwachman-Diamond syndrome, Fanconi anaemia and neurofibro-matosis type 1.


• Clonal haematopoietic stem cell disorder characterised by stepwise genetic progression possibly due to a combination of genetic predisposition and environmental exposures.

• Abnormalities in the marrow microenvironment described: e.g. aberrant cytokine production (increased inhibitory pro-apoptotic cytokines including TNF-a, IL-6, TGF-|3, IFN-gand Fas ligand) and altered stem cell adhesion.

• MDS marrow stem cells display lowered apoptotic threshold to TNF-a, IFN-g & anti-Fas antibodies and less response to haemopoietic growth factors.

• Early indolent pro-apoptotic MDS transforms to aggressive proliferative MDS as genetic lesions accumulate (ras, FLT3, FMS and p53 mutations associated with disease progression).

• Symptoms relate not only to the degree of cytopenia but to impaired function of granulocytes and platelets and may occur at near-normal or normal levels.

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