29th May 2023

Myelodysplastic syndromes (MDS)

Myelodysplastic syndromes comprise a group of heterogeneous conditions which share similar underlying features:

1. Malignant clonal proliferation of abnormal cells within the marrow
2. Dysplasia in at least one myeloid cell lineage
3. Ineffective haematopoiesis
4. Propensity to progression to AML

The bone marrow itself is often hypercellular but with ineffective haematopoiesis there is a reduction in healthy cell maturation and so cytopenias result.

It is generally considered a disease of the elderly and prevalence is increasing. 10% of MDS is secondary to exposure to mutagens, including chemo and radiotherapy but also environmental such as benzenes.

Symptoms are usually due to cytopenias:

• Erythroid – anaemia
• Platelets – bleeding
• Granulocytes – infection

Splenomegaly is possible.

Investigations

• Bloods – rule out other causes for cytopenias. Anaemia can be normocytic or macrocytic.
  • Blood film shows dysplastic features in at least one lineage (see image of a dysplastic neutrophil)
• Bone marrow – usually hypercellular with evidence of dysplasia. Blasts may be present (<20%)
• Cytogenetic analysis is important for risk stratification.

Blood film showing a dysplastic neutrophil – the cytoplasm is hypogranular and there is a pseudo-Pelger-Huet nucleus. The accompanying red cell changes in this case are actually a result of splenectomy.

Image Source: Wikimedia Commons (2021). Myelodysplasia, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Myelodysplasia.jpg (Accessed on: 10 January 2023).

Subtypes of MDS:

1. MDS with single lineage dysplasia
2. MDS with multi lineage dysplasia
3. MDS with ring sideroblasts
4. MDS with excess blasts 5-9%
5. MDS with excess blasts 10-19%
6. MDS with isolated del 5q

Some variants of MDS overlap with proliferative phenotypes (MDS/MPN overlap). They show features of both dysplasia and proliferation. Chronic myelomonocytic leukaemia (CMML) is an example.

Prognosis

The IPSS-R is a scoring system which guides prognosis. It is based on the severity of cytopenias, cytogenetic abnormalities and blast percentage. The risk of transformation to AML increases with each risk category.

Management

This is highly individualised and takes into account the severity of MDS, patient age and fitness for treatment. Elderly patients with low risk MDS are more likely to die with MDS than from it.

1. The only truly curative option for MDS is high dose chemotherapy, usually supported by allogeneic stem cell transplant. This option is reserved for high risk MDS and only in those fit enough.
2. Lower intensity chemotherapy such as azacytidine or lenalidomide
3. Supportive therapy
   1. Blood and platelet transfusions
   2. Growth factor support
   3. Antibiotics as necessary

Patients receiving regular transfusions of RBC are at risk for transfusion-associated iron overload and may require iron chelation therapy.