Haematology 8 - MDS + aplastic anaemia

Question 1

Define an MDS

Answer 1

Development of a clone of marrow stem cells with ineffective maturation –> functionally defective blood cells + low numbers

Question 2

Age group who get MDS

Answer 2

Elderly, develops over weeks-months

Question 3

Morphological features of MDS

Answer 3

Pelger-Huet anomaly (bilobed neutrophils)
Micromegakaryocytes
Dysgranulopoiesis of neutrophils
Increase proportion of blast cells in BM
Ringed sideroblasts
Myelokathexis - broken up nuclei joined together by thing string

Question 4

% blasdts in MDS?

Answer 4

<20%

Question 5

Cytogenetic abnormality in all pts with MDS?

Answer 5

5q deletion

Question 6

How is MDS prognosis calculated? Which score?

Answer 6

IPSS - % blasts, cytopenias + karyotype

Question 7

Death from MDS (rule of 1/3rds)

Answer 7

1/3 die from infection
1/3 die from bleeding
1/3 die from leukaemia

Question 8

Tx MDS (2 main options)

Answer 8

Allogenic SCT or intensive chemotherapy

Question 9

Tx MDS in elderly frail pts

Answer 9

1) supportive care (transfusions, antibiotics, iron chelation)
2) biological therapies (immunosuppression, lenalidomide)
3) chemotherapy

Question 10

Differentiate between MDS and aplastic anaemia

Answer 10

MDS = hypercellular BM, cytogenetic abnormality
AA = hypocellular BM, cytogenetics not important

Question 11

What is aplastic anaemia?

Answer 11

BM unable to produce adequate numbers of cells, mainly RBCs but can have a pancytopenia

Question 12

Classification of types of aplastic anaemia

Answer 12

Primary (congenital or acquired) and secondary

Question 13

Main causes of primary aplastic anaemia

Answer 13

Idiopathic (70%)

COngenital/ inherited- Fanconi’s anaemia, dyskeratosis congenita, Diamond blackfan, Schwachman diamond syndrome

Question 14

Causes of secondary aplastic anaemia

Answer 14

Radiation, SLE, drugs e.g. sulphonamides, chloramphenicol, carbamazepine

Question 15

Mx of aplastic anaemia (4 points)

Answer 15

1. Supportive therapy
2. Immunosuppressants
3. Drugs to promote marrow recovery
4. SCT

Question 16

What supportive tx used in AA?

Answer 16

Blood transfusions, Abx, iron chelation

Question 17

Immunosuppressants used in AA?

Answer 17

Anti thymocyte globulin, cyclosporine

Question 18

Drugs used in AA to promote BM recovery

Answer 18

Oxymethalone and growth factors

Question 19

Who will be offered SCT in AA and what is the success rate?

Answer 19

<40, sibling donor SCT success rate of ~80%

Question 20

Complications associated with immunosuppression in AA

Answer 20

Relapse, leukaemia/MDS, solid organ tumours

Question 21

Pathophysiology of idiopathic aplastic anaemia

Answer 21

Cytotoxic CD8+ T cells attack CD34 stem cells

Question 22

5-10 years old, pancytopenia, short thumbs

Answer 22

Fanconi’s anaemia

Question 23

modes of inheritance of Fanconi’s anaemia

Answer 23

AR or X-linked recessive

Question 24

Physical deformities in Fanconi’s anaemia?

Answer 24

SHort stature
Micro or hydrocephaly
Short thumbs
Skin pigmentation/ cafe au lait spots

Question 25

Dyskeratosis congenita most common mode of inheritance

Answer 25

X-linked recessive (or AD or AR, different genes for each)

Question 26

DC triad

Answer 26

Nail dystrophy, leukoplakia, skin pigmentation

Question 27

Genetics for Fanconi's

Answer 27

Issue with DNA repair

Question 28

Genetics for DC

Answer 28

Telomere shortening

Question 29

Other than DC, what other cause of aplastic anaemia also presents with telomere shortening?

Answer 29

Idiopathic aplastic anaemia

Question 30

Diamond blackfan anaemia - findings

Answer 30

Red cell anaemia only, features of microcephaly and cleft palate - presenst 1 year/neonatal

Question 31

Schwachman diamond syndrome which cell lines affected?

Answer 31

Primarily neutropenia + pancreatic insufficiency