Haematology 13 - Myelodysplastic syndromes and aplastic anaemias

Question 1

MDS vs aplastic anaemia

Answer 1

MDS = functional deficiency;

Aplastic anaemia = qualitative deficiency

Question 2

Recall the pathophysiology of Myelodysplasia

Answer 2

clone of marrow stem cells with abnormal maturation -> Functionally defective blood cells + Numerical reduction

->

Cytopaenia

Qualitative (functional) abnormalities of erythroid, myeloid and megakaryocyte maturation

Increased risk of transformation to leukaemia

BM failure

Question 3

What are the possible causes of death in myelodysplastic syndromes?

Answer 3

1/3 die of bleeding
1/3 die of infection
1/3 die of AML (AML from MDS = v poor prognosis)

Question 4

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

Answer 4

1. Allogenic stem cell transplant
2. Intensive chemotherapy
   Sadly, most patients can’t benefit from either for one reason or another

Question 5

What blood film abnormalities can you see in Myelodysplasia?

Answer 5

• Pelger-Huet anomaly
• Dysgranulopoeisis of neutrophils
• Dyserythropoiesis of red cells
• Ringed sideroblasts
• Dysplastic megakaryocytes

Question 6

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

Answer 6

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

• IMid (lenalidomide)

Question 7

How does azacytidine work in the treatment of myelodysplastic syndromes?

Answer 7

Hypomethylating agent
Causes blood count to rise

Question 8

What are the only treatments that pronlong surival in myelodysplastic syndrome?

Answer 8

allogeneic stem cell transplant (SCT

intensive chemo

• Oral → hydroxyurea

Low dose → SC low dose cytarabine

Intensive chemotherapy / A-SCT:

AML-type regimens

Allo/VUD standard/reduced intensity

Question 9

What are the causes of secondary aplastic anaemia?

Answer 9

1. BM infiltration
2. haem (leukaemia, lymphoma, myelofibrosis)
3. non haem - solid tumours
4. radiation
5. chemicals (benzene)
6. SLE
7. infection - parvovirus, hepatitis
8. drugs

VIRD (virus, immune, radiation, drugs)

Question 10

What are the causes of primary aplastic anaemia?

Answer 10

Congenital: Fanconi’s anaemia (multipotent stem cell)

Diamond-Blackfan anaemia (red cell progenitors)

Kostmann’s syndrome (neutrophil progenitors)

Acquired: Idiopathic aplastic anaemia (multipotent stem cell)

Question 11

Recall 3 drugs that can cause bone marrow failure

Answer 11

PREDICTABLE (dose-dependent, common)

Cytotoxic drugs

IDIOSYNCHRATIC (NOT dose-dependent, rare)

Phenylbutazone

Gold salts

chloramphenicol

NSAIDS

ANTIBIOTICS

Chloramphenicol

Sulphonamide

DIURETICS

Thiazides

ANTITHYROID DRUGS

carbimazole

Question 12

What is the age distribution of aplastic anaemia?

Answer 12

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

Question 13

Recall the pathophysiology of idiopathic aplastic anaemia

Answer 13

failure of BM to produce blood cells

“Stem cell” problem (CD34, LTC-IC) [Long-Term Culture-Initiating Cells]

Immune attack (humoral or cellular (T cell) attack against multipotent haematopoietic stem cell)

Question 14

What are the 2 classifications of aplastic anaemia?

Answer 14

Severe aplastic anaemia (SAA) or non-severe aplastic anaemia (NSAA)

Camitta criteria

Question 15

What will you see on the bone marrow of idiopathic aplastic anaemia?

Answer 15

hypocellular + fat

Question 16

How should idiopathic aplastic anaemia be treated?

Answer 16

For all patients: androgens (oxymethalone) - marrow recover

For older patients: immunosuppression
- anti-lymphocyte globulin
- ciclosporin
For younger patients: stem cell transplant

refractory - aletuzumab

same for Fanconi’s

Question 17

Recall some symtoms of Fanconi’s anaemia

Answer 17

Short Stature

Hypopigmented spots and café-au-lait spots

Abnormality of thumbs

Microcephaly or hydrocephaly

Hypogonadism

Developmental delay

Question 18

What is the triad of clinical features of dyskeratosis congenita?

Answer 18

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

Question 19

What is the genetic basis of dyskeratosis congenita?

Answer 19

Telomere shortening

telomeres at end of chromosomes prevent chromosomal fusion or rearrangements during replication and protect genes at end from degradation

Telomere length is reduced in bone marrow failure diseases (they are especially short in DC)

Question 20

What is the pseudo-pelger-huet anomaly?

Answer 20

Hyposegmented neutrophils seen in myelodysplastic syndromes

Question 21

Recall the options for treatment in essential thrombocytosis

Answer 21

1. Aspirin (to reduce thrombus formation)
2. Anagrelide (reduced formation of platelets from megakaryocytes)
3. Hydroxycarbamide

Question 22

Pattern of ingeritance in dyskeratosis congenita

Answer 22

3 patterns of inheritance:

X-linked recessive (MOST COMMON)

Mutant DKC1 gene leads to defective telomere functioning

Autosomal dominant

Mutant TERC gene – encodes the RNA component of telomerase

Autosomal recessive

Mutant gene has NOT been identified