Haem: Myelodysplastic syndromes and Aplastic anaemia Pt.1

Question 1

Define myelodysplastic syndrome.

Answer 1

Biologically heterogenous group of acquired haematological stem cell disorders

Question 2

What are the key characteristics of myelodysplastic syndromes?

Answer 2

Development of a clone of marrow stem cell with abnormal maturation resulting in

• Functionally defective blood cells
• Numerial reduction in cell counts

This leads to
1. Cytopaenia
2. Functional abnormalities of erythroid, myeloid, and megakaryocyte maturation
3. Increased risk of transformation to leukaemia

Question 3

Which types of patients tend to develop myelodysplastic syndromes?

Answer 3

Elderly

Question 4

How do myelodysplastic syndromes typically present?

Answer 4

Symptoms/signs of bone marrow failure developing over weeks/months

Question 5

List and describe some blood and bone marrow features of myelodysplastic syndromes - seen on blood film

Answer 5

• Pelger-Huet anomaly - bilobed neutrophils
• Dysgranulopoeisis of neutrophils - failure of granulation
• Dyserythropoiesis of red blood cells -lack of separation between red cell precursors (cytoplasmic bridge), presence of abnormal ring of cytoplasm around the nucleus of percursor red cells
• Dysplastic megakaryocytes - micro-megakaryocytes
• Increased proportion of blast cells in the bone marrow (normally < 5%)

Question 6

What does this image show?

Answer 6

Pelger-Huet anomaly
Nucleus appears bilobed or dumb-bell shaped

Normal neutrophils shown below

Question 7

What does this image show?

Answer 7

Refractory anaemia with dysgranulopoiesis - failure of neutrophil granulation

Question 8

What does this image show?

Answer 8

Refractory anaemia-dyserythropoiesis
- Lack of separation between red cell precursors
- Presence of abnormal blebby ring of cytoplasm around the nucleus of precursor red cells

Question 9

What does this image show?
Name the stain used

Answer 9

Ringed sideroblasts
- Accumulation of iron around the nuclei of red blood cell precursors
- Seen in refractory anaemia with ringed sideroblasts (RARS)

Seen on Prussian blue stain

Question 10

What is the presence of myeloblasts with Auer rods suggestive of?

Answer 10

Acute myeloid leukaemia.

Question 11

List the criteria of the WHO classification of MDS

Answer 11

Question 12

What are the five prognostic variables that are used to calculate prognostic risk using the Revised International Prognostic Scoring System (IPSS-R) for Myelodysplastic Syndromes?

Answer 12

The high risk is considered a score > 6, low risk ≤ 1.5
The higher the risk, the lower the survival and time to progress to AML

Question 13

How does myelodysplasia tend to evolve from the time of diagnosis?

Answer 13

• Blood count deterioration - leads to worsening bone marrow failure)
• Development of acute myeloid leukaemia - extremely poor prognosis

Question 14

What are the usual causes of death in patients with myelodysplasia?

Answer 14

• 1/3 infection
• 1/3 bleeding
• 1/3 leukaemia

Question 15

What are the two treatments that can prolong life in myelodysplastic syndromes?

Answer 15

• Allogeneic stem cell transplantation
• Intensive chemotherapy

NOTE: as most MDS patients are elderly, they often cannot tolerate treatment

Question 16

List some other treatments that may be used in myelodysplastic syndromes.

Answer 16

Supportive Care

• Blood products support
• Antimicrobials
• Growth factors e.g. EPO, G-CSF, TPO-agonist (eltrombopag)

Biological modifiers - treating underlying disease

• Immunosuppression
• Azacytidine or Decitabine (hypomethylating agent)
• Lenalidomide (used in del(5q) minus syndrome)

Oral chemotherapy (e.g. hydroxyurea) - if WCC is high (less common)

Low-dose chemotherapy (SC low-dose cytarabine) - not used now

Question 17

What is bone marrow failure a result of?

Answer 17

Results from damage or suppression of stem or progenitor cells

• Damage to pluripotent stem cell - impairs production of ALL peripheral blood cells
• Damage to committed progenitor cells - results in bi- or unicytopenias

Question 18

List some primary and secondary causes of bone marrow failure

Answer 18

Question 19

List some causes of primary aplastic anaemia

Answer 19

Acquired: idiopathic aplastic anaemia (MOST COMMON - 70-80%)

Congential (RARE):

• Fanconi anaemia (multipotent stem cell)
• Dyskeratosis congentia

Question 20

List some secondary causes of aplastic anaemia

Answer 20

• Radiation
• Drugs - cytotoxic drugs (predicable), chloramphenicol, NSAIDS (both idosyncratic)
• Autoimmune - SLE
• Infection - parvovirus B19, hepatitis, HIV

Question 21

List some drugs that can cause bone marrow failure.

Answer 21

• Cytotoxic drugs (predicatble, dose-dependent)
• Phenylbutazone, Gold salts (idiosyncratic, rare)
• Antibiotics - chloramphenicol, sulphonamides
• Diuretics - thiazide
• Antithyroid drugs - carbimazole

Question 22

What is aplastic anaemia

Answer 22

Hypocellular anaemia

(cytopenia without tumour etc in bone marrow)

Question 23

Which age groups are affected by aplastic anaemia?

Answer 23

All age groups can be affected - mainly 15-24 and 60+

NOTE: this is much more rare than MDS

Question 24

What is the most common cause of aplastic anaemia?

Answer 24

Idiopathic (70-80%)