MYELODYPLASTIC SYNDROME

Question 1

What is myelodysplastic syndrome?

Answer 1

Clonal haemopoietic disorders characterised by ineffective haemopoiesis resulting in peripheral blood cytopenia (especially anaemia). There is an increased risk of developing acute leukaemia.

Question 2

What age group is most commonly affected by myelodysplastic syndrome?

Answer 2

Elderly - 60-75 but it does affect younger people as well

Question 3

Are the majority of cases of myelodysplastic syndrome primary or secondary?

Answer 3

Primary

Question 4

What are the causes of secondary myelodysplastic syndrome?

Answer 4

Exposure to occupational chemicals especially benzene

Previous high dose chemotherapy (eg before bone marrow transplant) or radiotherapy

Question 5

How do secondary therapy related cases of myelodysplastic syndrome compare to cases of primary myelodysplastic syndrome?

Answer 5

Therapy related MDS involves:
More severe cytopenia
Occurrence at younger age
A higher rate of transformation into acute leukaemias
More clonal chromosomal abnormalities
A generally poorer prognosis

Question 6

What is the pathogenesis of myelodysplastic syndrome?

Answer 6

DNA damage of a pluripotent stem cell leads to development of myelodyplastic clone which has a growth advantage. Increased cellular proliferation within bone marrow results in hypercellular marrow. However, these cells do not differentiate properly and there is increased rate of apoptosis. Therefore, fewer mature cells leave the bone marrow, resulting cytopenia.

Question 7

How might someone with myelodysplastic syndrome present?

Answer 7

Often asymptomatic and found on incedental FBC

Signs and symptoms of pan-cytopenia: fatigue, shortness of breath, bleeding, infection

Question 8

What investigations should be ordered for someone with suspected myelodysplastic syndrome?

Answer 8

FBC
Blood film
B12
Folate
Bone marrow aspirate and trephine biopsy
Cytogenetics - presence of same cytogenic abnormality in multiple cells in the marrow

Question 9

What are the changes seen on a blood film of someone with myelodysplastic syndrome?

Answer 9

Red cells:
Macrocytosis
Anisocytosis (abnormal size)
Poikilocytosis (abnormal shape)
Basophilic stippling

White cells:
Hypogranular
Unusual nuclear shape

Platelets;
Hypogranular

Question 10

What are the three main types of myelodysplastic syndrome?

Answer 10

Refractory anaemia

Refractory anaemia with ringed sideroblasts

Refractory anaemia with excess blasts

Question 11

What are the changes that might be seen on bone marrow biopsy from someone with myelodysplastic syndrome?

Answer 11

Ringed sideroblasts
Increased blasts
Megakaryocytes with separated nuclei

Question 12

What is the prognosis of someone diagnosed with myelodysplastic syndrome?

Answer 12

6 months to 6 years

Question 13

How are myelodysplatic syndrome patients managed?

Answer 13

Supportive transfusions of red cells and platelets
EPO injections may reduce number of transfusions needed - particularly useful in refractory anaemia with ringed sideroblasts
Immunosuppressives such as ciclosporins or antithymocyte globulins
Allogeneic stem cell transplant

Question 14

What is the genetic abnormality associated with myelodysplastic syndrome in middle aged woman which is associated with a longer survival and a lower risk of transformation into acute myeloid leukaemia?

Answer 14

Loss of the long arm of chromosome 5

Question 15

What drug is useful in treating patients with myelodysplastic syndrome associated with 5q- (loss of long arm of chromosome 5)?

Answer 15

Thalidomide analogues such as lenalidomide