Myelodysplastic syndromes

Myelodysplastic and myeloproliferative disorders

Myelodysplastic syndromes

Definition

Myelodysplastic syndrome (MDS) is a premalignant condition  in  which  there  are  abnormal  stem  cells resulting in production of abnormal cells, anaemia, neutropenia and thrombocytopenia.

Incidence

20 per 100,000 per year over the age of 70 years.

Age

More than 80% of patients are over the age of 60 years.

Sex

M>F

Aetiology

Myelodysplastic syndromes are classified using the WHO classification dependent on the peripheral blood and bone marrow findings into:

·        Refractory anaemia (RA).

·        Refractory anaemia with ringed sideroblasts (RARS).

·        Refractory cytopenia with multilineage dysplasia(RCMD).

·        Refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS).

·        Refractory anaemia with excess blasts-1 (RAEB-1).

·        Refractory anaemia with excess blasts-2 (RAEB-2).

·        Myelodysplastic syndrome, unclassified (MDS-U).

·        MDS associated with isolated deletion (5q).

Pathophysiology

The disorder arises from a single abnormal stem cell. MDS is initially indolent due to inhibitory cytokines, however over time oncogenes are activated and tumour suppressor genes inactivated resulting in a proproliferative aggressive condition which may progress to acute myeloid leukaemia. Dysplastic stem cells are refractory to haemopoetic growth factors resulting in a peripheral cytopenia.

Clinical features

Patients with myelodysplastic syndrome typically present with symptoms of anaemia, thrombocytopenia (spontaneous bruising and petechiae or mucosal bleeding) or leucopenia (recurrent infections of the skin, mucosal surfaces or lungs).

Investigations

Bone marrow aspirate examination shows normal or increased cellularity with megaloblastic cells and sometimes ring sideroblasts and abnormal myeloblasts.

Management

Supportive therapy includes red blood cell and platelet transfusions and the use of antibiotics for infections. Allogeneic stem cell transplantation is potentially curative but is only used in the rare cases arising in young patients. In older patients chemotherapy may be used especially in the more aggressive forms of MDS. Patients with less aggressive forms of MDS may benefit from the use of haemopoetic growth factors.