Haematology 7: Myelodysplastic Syndrome

Question 1

What are the haematological features of Myelodysplastic syndrome ?

Answer 1

Cytopaenias
Qualitative abnormalities of erythrocytes, myelocytes and megakaryocytes maturation
increased risk of transformation into leukaemia

Question 2

Name the characteristic bilobed neutrophil seen in MDS ?

Answer 2

Pseudo Pelger-huet anomaly

Question 3

List some abnormal cells seen with microscopy in MDS ?

Answer 3

Pseudo Pelger huet neutrophils (bilobed)
Dysgranulosis of neutrophils
Dyserythropoiesis of red cells
Ringed sideroblasts - iron granules visible
Micro megakaryocytes ( dysplastic megakaryocytes)
Increased proportion of blast cells in marrow
Myeloblasts with auer rods (also feature of AML)

Question 4

Which disease does MDS often progress to ?

Answer 4

AML

Question 5

Which drug can be used to treat MDS 5q- syndrome ?

Answer 5

Lenalidomide

Question 6

List 3 Primary causes of bone marrow failure ?

Answer 6

Fanconi’s anaemia
Diamond blackfan anaemia
Kostmann’s syndrome
Acquired: idiopathic aplastic anaemia

Question 7

Which 2 antibiotics can cause bone marrow failure ?

Answer 7

Chloramphenicol

Sulphonamide

Question 8

How is fanconi anaemia inherited ?

Answer 8

Mainly autosomal recessive but some are X linked

Question 9

List 4 congenital abnormalities seen in children with Fanconi anaemia ?

Answer 9

Absent radii
Abnormal thumbs
Cafe au lait spots
Short stature

Question 10

What is the pathognomonic triad of clinical signs of Dyskeratosis Congenital (DC)?

Answer 10

Skin pigmentation
Nail dystrophy
Leukoplakia

These children look very old! The disease causes premature aging

Question 11

What is the genetic cause of Dyskeratosis congenita ?

Answer 11

Mutation in Genes that encode proteins involved in maintenance of telomerases. These telomerases get shortened at the ends. This causes premature ageing

Question 12

define myelodysplastic syndrome

Answer 12

biologically heterogeneous group of acquired haematopoietic stem cell disorders
characterised by development of a clone of marrow stem cells with abnormal maturation resulting in:
- functionally defective blood cells
- numerical reduction
usually elderly
develops over weeks/months

Question 13

prognosis of patients with MDS

Answer 13

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

Question 14

treatment options for MDS

Answer 14

allogenic stem cell transplant
intensive chemotherapy
supportive - blood products, antimicrobial, growth factors
biological modifiers - immunosuppressive agents, azacytidine, decitabine, lanalidomide
oral chemotherapy - hydroxyurea/hydroxycarbamide
low dose chemo - subcutaneous low-dose cytarabine
intensive chemo/stem cell transplant - for high risk MDS - AML-type regimes

Question 15

secondary causes of bone marrow failure

Answer 15

marrow infiltration 
haematological malignancies (leukaemias, lymphomas)
non-haematological (solid tumours)
radiation 
drugs
chemicals (eg benzene)
AI 
infection (parovirus, viral hepatitis)

Question 16

what drugs can cause bone marrow failure

Answer 16

predictable - cytotoxic drugs
idiosyncratic - phenylbutazone, gold salts
antibiotics - chloramphenicol, sulphonamide
diuretics - thiazides
antithyroid drugs - carbimazole

Question 17

what is aplastic anaemia

Answer 17

deficiency of RBC, WBC, and platelets
all age groups affected
bimodal incidence - 15-24, 60+

Question 18

what are the different types of aplastic anaemia

Answer 18

most = idiopathic 
inherited = dyskeratosis congenita, fanconi anaemia, schwachman- diamond syndrome 
secondary = radiation, drugs, hepatitis viruses, SLE

Question 19

describe the clinical presentation of bone marrow failure

Answer 19

anaemia - fatigue, breathlessmess
leucopaenia - infections
thrombocytopeania - bleeding/ bruising

Question 20

how is aplastic anameia diagnosed

Answer 20

peripheral blood - cytopeania

bone marrow - hypocellular

Question 21

what are the two subtypes of aplastic anaemia

Answer 21

severe aplastic anaemia (SAA)

non-severe aplastic anaemia (NSAA)

Question 22

what is the camitta criteria for severe aplastic anaemia

Answer 22

2/3 peripheral blood features

• reticulocytes <1% (<20 x 109/l)
• neutrophils <0.5 x 109/l
• platelets <20 x 109/l

Question 23

how is bone marrow failure managed

Answer 23

seek and remove cause 
supportive - blood transfusion/ platelet transfusion 
iron chelation therapy 
immunosuppressive therapy 
SC transplant (younger patients)

Question 24

describe features of fanconi anaemia

Answer 24

most common AA
autosomal recessive/ x linked
multiple mutated genes involved 
gene mutations result in:
- abnormalities in DNA repair 
- chromosomal fragility 
- breakage in the presence of in vitro mitomycin/ diepoxybutane

Question 25

what are clinical features of fanconi anaemia

Answer 25

short stature
hypopigmented spots and cafe au lait spots 
abnormality of thumbs 
microcephaly or hydrocephaly 
hypogonadism 
developmental delay 
no abnormalities in 30%

Question 26

list complications of fanconi anaemia

Answer 26

aplastic anaemia 
leukaemia
liver disease 
myelodysplasoa
cancer (epithelial)

Question 27

what is dyskaryosis congenita

Answer 27

inherited disorder characterised by:

• marrow failure
• cancer predisposition
• somatic abnormalities

Question 28

how do patients with dyskaryosis congenita present

Answer 28

skin pigmentation
nail dystrophy
leukoplakia

Question 29

list somatic abnormalities/complications in DC

Answer 29

abnormal skin pigmentation
nail dystrophy
BM failure
leukoplakia

Question 30

what is the genetic basis of dyskaryosis congenita

Answer 30

telomere shortening
3 patterns of inhetritance:
- X-linked recessive (most common) - mutant DKC1 gene leads to ineffective telomere functioning
- Autosomal dominant - mutant TREC gene - encodes RNA component of telomerase
- Autosomal recessive - ? mutant gene

Question 31

what is the function of telomeres

Answer 31

prevent chromosomal fusion or rearrangements during chromosomal replication
protects genes at end of chromosomes from degrading
telomere length reduced in BM failure diseases

Question 32

how is severe aplastic anaemia treated

Answer 32

age <35:
- HLA identical sibling donor/child or unrelated donor
age 35-50:
- HLA donor or horse anti-thymocyte gobulin (ATG_ + ciclosporin) - unrelated HCA donor/ eltrombopag + 2nd ATG