Haematology 13 - Myelodysplastic syndromes and aplastic anaemias

Question 1

What are the possible causes of death in myelodysplastic syndromes?

Answer 1

1/3 die of bleeding
1/3 die of infection
1/3 die of AML

Question 2

What are the 2 possible curative treatments for myelodysplastic syndromes, and what is the biggest issue with them?

Answer 2

1. Allogenic stem cell transplant
2. Intensive chemotherapy
   Sadly, most patients can’t benefit from either (very elderly, difficult for them to undergo such aggressive treatments)

Question 3

In myelodysplastic syndrome patients who are not suitable for curative treatment, how should disease be managed?

Answer 3

Supportive treatments include: 
- Blood products
- Antibiotics
- GF
Can add biological modifiers: 
- Immunosuppressive therapy
- Azacytidine

Question 4

How does azacytidine work in the treatment of myelodysplastic syndromes?

Answer 4

Hypomethylating agent

Stops abnormal proliferation- helps increase quantities of normal cells

Question 5

Recall drugs that can cause bone marrow failure

Answer 5

• Predictable (dose-dependent, common)
o Cytotoxic drugs

• Idiosyncratic (not dose-dependent, rare)
o Phenylbutazone
o Gold salts

• Antibiotics
o Chloramphenicol
o Sulphonamide

• Diuretics
o Thiazides

• Antithyroid drugs
o Carbimazole

Question 6

What is the age distribution of aplastic anaemia?

Answer 6

Bimodal
Peak 1: 15-24 years
Peak 2: >60 years

Question 7

What are the possible causes of aplastic anaemia

Answer 7

o Idiopathic
 Vast majority (70-80%)

o Congenital/ Inherited
 Dyskeratosis congenita (DC)
 Fanconi anaemia (FA)
 Schwachman-Diamond syndrome

o Acquired
 Radiation – Predictable

 Drugs
• Predictable – Cytotoxic agents
• Idiosyncratic – Chloramphenicol, NSAIDs

 Viruses – hepatitis viruses (idiosyncratic)

 Immune – SLE
o Miscellaneous

 PNH (paroxysmal nocturnal haemoglobinuria)

 Thymoma

Question 8

What are the 2 classifications of aplastic anaemia, and how is classification decided?

Answer 8

Severe or non-severe
Decided by Camitta criteria:
- Aplastic anaemia is severe if 2 or more of the following peripheral blood features are present:
- Reticulocytes <1%
- Neutrophils <0.5
- Platelets <20
PLUS: Bone marrow cellularity must be <25%

Question 9

How should idiopathic aplastic anaemia be treated?

Answer 9

For all patients: androgens (oxymethalone)- upregulates telomerase-enhances BM activity
For older patients: immunosuppression
- anti-lymphocyte globulin
- ciclosporin
For younger patients: stem cell transplant

Question 10

Recall some symtoms of Fanconi’s anaemia

Answer 10

Short stature, hypogonadism, thumb abnormality, cafe au lait spots (due to abnormal mutated genes)

Question 11

What is the triad of clinical features of dyskeratosis congenita?

Answer 11

1. Skin pigmentation
2. Nail dystrophy
3. Oral leukoplakia
   “SNOB” = the above triad + BM failure - useful mnemonic

Question 12

What is the genetic basis of dyskeratosis congenita?

Answer 12

Telomere shortening

Question 13

What is the pseudo-pelger-huet anomaly?

Answer 13

Hyposegmented neutrophils seen in myelodysplastic syndromes (bilobed)

Question 14

Recall the options for treatment in essential thrombocytosis

Answer 14

1. Aspirin (to reduce thrombus formation)
2. Anagrelide (reduced formation of platelets from megakaryocytes)
3. Hydroxycarbamide (inhibits dna synthesis- also increases foetal haemoglobin)

Question 15

Good prognostic factors in MDS

Answer 15

5q, 20q deletion

^more common in females

Question 16

Poor prognostic factors in MDS

Answer 16

high/increasing percentage of blasts
high number of cytopenias
increasing age
cytogenic anomalies on chromosome 7

Question 17

MDS vs aplastic anaemia

Answer 17

both have cytopenias

but MDS is hypercellular marrow while aa is hypocellular

Question 18

diagnostic findings of MDS

Answer 18

FBC: pancytopenia, decreased reticulocyte count and increased MCV because immature cells are larger
Peripheral smear: pelger huet abnormalities, basophilic stipling of RBCs, large agranular platelets, ringed sideroblasts
Bone marrow biopsy: <20% blasts, hypercellular marrow, dysplasia and pancytopenia

Question 19

aplastic anaemia bone marrow biopsy:

Answer 19

hypocellularity: fat and stroma, haematopoetic cells <25% of bone marrow
no malignant or fibrotic cells (would point to myelofibrosis instead)
morphologically normal remaining haematopoetic cells